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Vitale SG, Angioni S, D'Alterio MN, Ronsini C, Saponara S, De Franciscis P, Riemma G. Risk of endometrial malignancy in women treated for breast cancer: the BLUSH prediction model - evidence from a comprehensive multicentric retrospective cohort study. Climacteric 2024; 27:482-488. [PMID: 39023103 DOI: 10.1080/13697137.2024.2376189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 06/11/2024] [Accepted: 06/30/2024] [Indexed: 07/20/2024]
Abstract
OBJECTIVE This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model. DESIGN A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer-Lemeshow test. RESULTS One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer-Lemeshow test (χ2 = 26.36; p = 0.999). CONCLUSIONS Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding.
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Affiliation(s)
- Salvatore Giovanni Vitale
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - Stefano Angioni
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - Maurizio Nicola D'Alterio
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - Carlo Ronsini
- Obstetrics and Gynecology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Stefania Saponara
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - Pasquale De Franciscis
- Obstetrics and Gynecology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania 'Luigi Vanvitelli', Naples, Italy
| | - Gaetano Riemma
- Obstetrics and Gynecology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania 'Luigi Vanvitelli', Naples, Italy
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Aslan K, Kabakçı M, Zengin Aksel T, Atalay F. Is It Possible to Prevent Nontherapeutic Laparotomies in Breast Cancer Patients With Isolated Adnexal Masses? Am Surg 2024:31348241265145. [PMID: 39033518 DOI: 10.1177/00031348241265145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
Introduction: The risk of ovarian malignancy is increasing in patients with a history of breast cancer. Thus, well-defined predictors of ovarian malignancy should be identified to determine surgical or conservative management of adnexal masses in women with breast cancer. This study aimed to clarify the predictors of malignant ovarian tumors in patients with breast cancer with an isolated adnexal mass. Methods: Breast cancer patients diagnosed with an adnexal mass who underwent surgery between 2010 and 2021 at a tertiary cancer center were included in the study. Patients with suspected extra ovarian metastases were excluded. Results: A total of 40 breast cancer patients who underwent surgery for ovarian masses were identified. 23 (57.5%) women had benign ovarian tumors and 17 (42.5%) had malignant ovarian tumors. Among the malignant ovarian tumors, there were three (17.6%) metastatic breast cancers in the ovary and 14 (82.4%) primary ovarian cancers. In univariate analyses, the risk of malignant ovarian tumors increased in women with age >52 years (P = .012), postmenopausal status (P = .023), CA 125 ≥ 35 IU/ml (P = .001), CA 15-3 ≥ 32 IU/ml (P = .002), and complex ovarian masses (P < .001). Ovarian malignancies were observed in 82.4% of patients who had complex ovarian masses. Conclusion: Ovarian malignancies were diagnosed in 82.4% of the breast cancers who had complex ovarian mass on USG examination. Therefore, surgery is recommended in women with complex ovarian masses. Postmenopausal status, age >52 years, CA 125 ≥ 35 IU/ml, and CA 15-3 ≥ 32 were other risk factors for ovarian malignancy.
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Affiliation(s)
- Koray Aslan
- Department of Gynecologic Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Faculty of Medicine, University of Health Sciences, Ankara, Turkey
| | - Mükiye Kabakçı
- Department of Gynecologic Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Faculty of Medicine, University of Health Sciences, Ankara, Turkey
| | - Tuba Zengin Aksel
- Department of Gynecologic Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Faculty of Medicine, University of Health Sciences, Ankara, Turkey
| | - Funda Atalay
- Department of Gynecologic Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Faculty of Medicine, University of Health Sciences, Ankara, Turkey
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Cignarella A, Bolego C, Barton M. Sex and sex steroids as determinants of cardiovascular risk. Steroids 2024; 206:109423. [PMID: 38631602 DOI: 10.1016/j.steroids.2024.109423] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 04/08/2024] [Accepted: 04/14/2024] [Indexed: 04/19/2024]
Abstract
There are considerable sex differences regarding the risk of cardiovascular disease (CVD), including arterial hypertension, coronary artery disease (CAD) and stroke, as well as chronic renal disease. Women are largely protected from these conditions prior to menopause, and the risk increases following cessation of endogenous estrogen production or after surgical menopause. Cardiovascular diseases in women generally begin to occur at a later age than in men (on average with a delay of 10 years). Cessation of estrogen production also impacts metabolism, increasing the risk of developing obesity and diabetes. In middle-aged individuals, hypertension develops earlier and faster in women than in men, and smoking increases cardiovascular risk to a greater degree in women than it does in men. It is not only estrogen that affects female cardiovascular health and plays a protective role until menopause: other sex hormones such as progesterone and androgen hormones generate a complex balance that differentiates heart and blood vessel function in women compared to men. Estrogens improve vasodilation of epicardial coronary arteries and the coronary microvasculature by augmenting the release of vasodilating factors such as nitric oxide and prostacyclin, which are mechanisms of coronary vasodilatation that are more pronounced in women compared to men. Estrogens are also powerful inhibitors of inflammation, which in part explains their protective effects on CVD and chronic renal disease. Emerging evidence suggests that sex chromosomes also play a significant role in shaping cardiovascular risk. The cardiovascular protection conferred by endogenous estrogens may be extended by hormone therapy, especially using bioidentical hormones and starting treatment early after menopause.
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Affiliation(s)
| | - Chiara Bolego
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Matthias Barton
- Molecular Internal Medicine, University of Zürich, Zürich, Switzerland; Andreas Grüntzig Foundation, Zürich, Switzerland.
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Abboud K, Umoru G, Trachtenberg B, Ajewole V. Real-world data of cardio-oncologic interventions for cardiovascular adverse events with oral oncolytics. CARDIO-ONCOLOGY (LONDON, ENGLAND) 2024; 10:22. [PMID: 38594785 PMCID: PMC11003064 DOI: 10.1186/s40959-024-00221-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 03/11/2024] [Indexed: 04/11/2024]
Abstract
BACKGROUND Oral cancer therapy-related cardiovascular (CV) toxicity has a wide variety of presentations including arrhythmia, cardiomyopathy, and myocardial infarction, but clinical evidence related to its management is limited. The purpose of this IRB-approved, single-center, retrospective, cohort study was to characterize cardio-oncologic interventions for CV adverse events related to oral oncolytics. METHODS The cohort included 67 patients who were admitted to a multi-hospital health system between June 1, 2016 and July 31, 2021, had at least one medical record order of oral oncolytics considered to have cardiotoxic potential, and had an ICD10 code for a cardiotoxic event added to their electronic medical records after initiation of oral oncolytics. RESULTS The majority (97%) had pre-existing cardiovascular disease (CVD) or a CV risk factor. The three most common classes of oral oncolytics were aromatase inhibitors (36%), BCR-ABL inhibitors (16%), and VEGFR inhibitors (13%). New-onset or worsening heart failure (HF) (n = 31), which occurred after a median of 148 days (Interquartile range (IQR) 43-476 days) was the most common cardiotoxic event. The most frequent interventions were pharmacological treatment of the CV adverse event (n = 44) and treatment interruption (n = 18), but guideline-directed medication therapy for HF could be further optimized. CONCLUSION Pre-existing CVD or CV risk factors predispose oncology patients to CV adverse events. Real-world practice reveals that CV adverse events require temporary interruption of treatment and initiation of pharmacologic treatment. A multidisciplinary, patient-centered approach that includes discussion of risks/benefits of treatment continuation, and initiation of guideline-directed treatment is recommended until high-quality, drug-specific data for monitoring and treatment become available.
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Affiliation(s)
- Karen Abboud
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA
| | - Godsfavour Umoru
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA
| | - Barry Trachtenberg
- Heart Failure and Transplantation Cardiology, Houston Methodist Hospital, Houston, TX, USA
| | - Veronica Ajewole
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA.
- Texas Southern University College of Pharmacy & Health Sciences, Houston, TX, USA.
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Ho I, Wong CK, Wong YK, Lam TH, Sze-Him Leung I, Lin M, Tak-Wai Lui D, Kwok WC, Tam CC, Chan YH, Chan EW, Tse HF. Aromatase Inhibitor Therapy Increases the Risk of New-Onset Atrial Fibrillation in Patients With Breast Cancer. JACC. ASIA 2024; 4:150-160. [PMID: 38371283 PMCID: PMC10866735 DOI: 10.1016/j.jacasi.2023.09.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 02/20/2024]
Abstract
Background Previous studies suggest that aromatase inhibitors (AIs) increase the risk of adverse cardiovascular events and cardiac arrhythmias in patients with breast cancer, but it is unclear whether AIs also increase the risk of new-onset atrial fibrillation (AF). Objectives The purpose of this study was to investigate whether the use of AIs was associated with an increased risk of new-onset AF in patients with breast cancer. Methods We performed a retrospective analysis involving 5,707 patients with breast cancer (mean age 63.9 ± 11.2 years and 99.9% women) who received adjunctive hormone therapy with an AI (AI group, n = 4,878) or tamoxifen (tamoxifen group, n = 829) in Hong Kong between January 1, 1999, and December 31, 2020. After propensity score matching, there were 1,658 and 829 patients with balanced characteristics in the AI group and tamoxifen group, respectively. Results After 8,863 patient-years of follow-up, patients who were prescribed AI had a trend toward more new-onset arrhythmias compared with those prescribed tamoxifen (0.62 vs 0.30 per 100 patient-years; crude HR: 2.05; P = 0.053). The difference in arrhythmic risk was mainly driven by a higher incidence rate of new-onset AF in the AI group (0.59 vs 0.27 per 100 patient-years; crude HR: 2.18; P = 0.046). The use of AIs was confirmed to be an independent risk factor for new-onset AF on multivariate analysis (adjusted HR: 2.75; P = 0.01). Conclusions Among breast cancer patients prescribed adjunctive hormonal therapy, AI was associated with an increased risk of new-onset AF. Regular surveillance for new-onset AF should be considered in breast cancer patients treated with an AI.
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Affiliation(s)
- Isaac Ho
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong SAR
| | - Chun-Ka Wong
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Yuen-Kwun Wong
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Tsun-Ho Lam
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | | | - Minqing Lin
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - David Tak-Wai Lui
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Wang Chun Kwok
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Chor-Cheung Tam
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Yap-Hang Chan
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Esther W.Y. Chan
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
| | - Hung-Fat Tse
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
- Cardiac and Vascular Center, Hong Kong University Shenzhen Hospital, Shenzhen, China
- Center for Translational Stem Cell Biology, Hong Kong SAR, China
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Saeki H, Horimoto Y, Hlaing MT, Men Y, Rong L, Ishizuka Y, Uomori T, Yoshida E, Terao Y, Arakawa A, Saito T, Yao T. Clinicopathological and molecular pathological characteristics in tamoxifen‑related endometrial cancer. Oncol Lett 2024; 27:9. [PMID: 38034487 PMCID: PMC10688500 DOI: 10.3892/ol.2023.14142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 09/21/2023] [Indexed: 12/02/2023] Open
Abstract
Tamoxifen (TAM), a selective estrogen receptor modulator, is often used for long-term adjuvant endocrine therapy in patients with hormone receptor-positive breast cancer. TAM is known to increase the risk of endometrial cancer (EC); however, the mechanism has not yet been fully elucidated. Therefore, molecular genetic analysis of EC following TAM administration (TAM-related EC) was conducted. A total of 10 samples of TAM-related EC and 20 sporadic EC samples (as controls) were analyzed. Copy number variation analysis was conducted, microsatellite instability (MSI) status was assessed, and mismatch repair (MMR) protein expression was examined immunohistochemically. Copy number variation analysis revealed that KDR, NOTCH1, NTRK1, NTRK3 and PDGFRB were more frequently amplified in TAM-related EC (P=0.039, P<0.001, P=0.011, P=0.006 and P=0.035, respectively). In MSI analysis, 4 cases were classified as MSI-high (40%), which is a higher frequency compared with that among patients with sporadic EC (~10% in Japanese women). Loss of MMR proteins was confirmed in all MSI-high cases. In 1 MSI-high case, a benign lesion of hyperplasia prior to EC development was also MSI-high with loss of some MMR protein expression. Several genes were specifically amplified in TAM-related ECs. Furthermore, TAM-related ECs were frequently MSI-high. Further studies are required to be conclusive; however, the present findings may lead to a reduction of unnecessary gynaecological testing in clinical practice and also encourage the testing for MSI status for optimal individualized treatment.
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Affiliation(s)
- Harumi Saeki
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
| | - Yoshiya Horimoto
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
- Department of Breast Oncology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
| | - May Thinzar Hlaing
- Department of Breast Oncology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
| | - Yuan Men
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
| | - Lu Rong
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
| | - Yumiko Ishizuka
- Department of Breast Oncology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
| | - Toshitaka Uomori
- Department of Breast Oncology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
| | - Emiko Yoshida
- Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
| | - Yasuhisa Terao
- Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
| | - Atsushi Arakawa
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
| | - Tsuyoshi Saito
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University Faculty of Medicine, Tokyo 113-0033, Japan
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
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7
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Emons G, Steiner E, Vordermark D, Uleer C, Paradies K, Tempfer C, Aretz S, Cremer W, Hanf V, Mallmann P, Ortmann O, Römer T, Schmutzler RK, Horn LC, Kommoss S, Lax S, Schmoeckel E, Mokry T, Grab D, Reinhardt M, Steinke-Lange V, Brucker SY, Kiesel L, Witteler R, Fleisch MC, Heinrich Prömpeler † 25, Friedrich M, Höcht S, Lichtenegger W, Mueller M, Runnebaum I, Feyer P, Hagen V, Juhasz-Böss I, Letsch A, Niehoff P, Zeimet AG, Battista MJ, Petru E, Widhalm S, van Oorschot B, Panke JE, Weis J, Dauelsberg T, Haase H, Beckmann MW, Jud S, Wight E, Prott FJ, Micke O, Bader W, Reents N, Henscher U, Reina Tholen † 52, Schallenberg M, Rahner N, Mayr D, Kreißl M, Lindel K, Mustea A, Strnad V, Goerling U, Bauerschmitz GJ, Langrehr J, Neulen J, Ulrich UA, Nothacker MJ, Blödt S, Follmann M, Langer T, Wenzel G, Weber S, Erdogan S. Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures. Geburtshilfe Frauenheilkd 2023; 83:919-962. [PMID: 37588260 PMCID: PMC10427205 DOI: 10.1055/a-2066-2051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 06/22/2023] [Indexed: 08/18/2023] Open
Abstract
Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.
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Affiliation(s)
- Günter Emons
- Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
| | - Eric Steiner
- Frauenklinik GPR Klinikum Rüsselsheim am Main, Rüsselsheim, Germany
| | - Dirk Vordermark
- Universität Halle (Saale), Radiotherapie, Halle (Saale), Germany
| | - Christoph Uleer
- Facharzt für Frauenheilkunde und Geburtshilfe, Hildesheim, Germany
| | - Kerstin Paradies
- Konferenz onkologischer Kranken- und Kinderkrankenpfleger (KOK), Hamburg, Germany
| | - Clemens Tempfer
- Frauenklinik der Ruhr-Universität Bochum, Bochum/Herne, Germany
| | - Stefan Aretz
- Institut für Humangenetik, Universität Bonn, Zentrum für erbliche Tumorerkrankungen, Bonn, Germany
| | | | - Volker Hanf
- Frauenklinik Nathanstift – Klinikum Fürth, Fürth, Germany
| | | | - Olaf Ortmann
- Universität Regensburg, Fakultät für Medizin, Klinik für Frauenheilkunde und Geburtshilfe, Regensburg, Germany
| | - Thomas Römer
- Evangelisches Klinikum Köln Weyertal, Gynäkologie Köln, Köln, Germany
| | - Rita K. Schmutzler
- Universitätsklinikum Köln, Zentrum Familiärer Brust- und Eierstockkrebs, Köln, Germany
| | | | - Stefan Kommoss
- Universitätsklinikum Tübingen, Universitätsfrauenklinik Tübingen, Tübingen, Germany
| | - Sigurd Lax
- Institut für Pathologie, LKH Graz Süd-West, Graz, Austria
| | | | - Theresa Mokry
- Universitätsklinikum Heidelberg, Diagnostische und Interventionelle Radiologie, Heidelberg, Germany
| | - Dieter Grab
- Universitätsklinikum Ulm, Frauenheilkunde und Geburtshilfe, Ulm, Germany
| | - Michael Reinhardt
- Klinik für Nuklearmedizin, Pius Hospital Oldenburg, Oldenburg, Germany
| | - Verena Steinke-Lange
- MGZ – Medizinisch Genetisches Zentrum München, München, Germany
- Medizinische Klinik und Poliklinik IV, LMU München, München, Germany
| | - Sara Y. Brucker
- Universitätsklinikum Tübingen, Universitätsfrauenklinik Tübingen, Tübingen, Germany
| | - Ludwig Kiesel
- Universitätsklinikum Münster, Frauenklinik A Schweitzer Campus 1, Münster, Germany
| | - Ralf Witteler
- Universitätsklinikum Münster, Frauenklinik A Schweitzer Campus 1, Münster, Germany
| | - Markus C. Fleisch
- Helios, Universitätsklinikum Wuppertal, Landesfrauenklinik, Wuppertal, Germany
| | | | - Michael Friedrich
- Helios Klinikum Krefeld, Klinik für Frauenheilkunde und Geburtshilfe, Krefeld, Germany
| | - Stefan Höcht
- XCare, Praxis für Strahlentherapie Saarlouis, Saarlouis, Germany
| | - Werner Lichtenegger
- Universitätsmedizin Berlin, Frauenklinik Charité, Campus Virchow-Klinikum, Berlin, Germany
| | - Michael Mueller
- Universitätsklinik für Frauenheilkunde, Inselspital Bern, Bern, Switzerland
| | | | - Petra Feyer
- Vivantes Klinikum Neukölln, Klinik für Strahlentherapie und Radioonkologie, Berlin, Germany
| | - Volker Hagen
- Klinik für Innere Medizin II, St.-Johannes-Hospital Dortmund, Dortmund, Germany
| | | | - Anne Letsch
- Universitätsklinikum Schleswig Holstein, Campus Kiel, Innere Medizin, Kiel, Germany
| | - Peter Niehoff
- Strahlenklinik, Sana Klinikum Offenbach, Offenbach, Germany
| | - Alain Gustave Zeimet
- Medizinische Universität Innsbruck, Universitätsklinik für Gynäkologie und Geburtshilfe, Innsbruck, Austria
| | | | - Edgar Petru
- Med. Univ. Graz, Frauenheilkunde, Graz, Austria
| | | | - Birgitt van Oorschot
- Universitätsklinikum Würzburg, Interdisziplinäres Zentrum Palliativmedizin, Würzburg, Germany
| | - Joan Elisabeth Panke
- Medizinischer Dienst des Spitzenverbandes Bund der Krankenkassen e. V. Essen, Essen, Germany
| | - Joachim Weis
- Albert-Ludwigs-Universität Freiburg, Medizinische Fakultät, Tumorzentrum Freiburg – CCCF, Freiburg, Germany
| | - Timm Dauelsberg
- Universitätsklinikum Freiburg, Klinik für Onkologische Rehabilitation, Freiburg, Germany
| | | | | | | | - Edward Wight
- Frauenklinik des Universitätsspitals Basel, Basel, Switzerland
| | - Franz-Josef Prott
- Facharzt für Radiologie und Strahlentherapie, Wiesbaden, Wiesbaden, Germany
| | - Oliver Micke
- Franziskus Hospital Bielefeld, Klinik für Strahlentherapie und Radioonkologie, Bielefeld, Germany
| | - Werner Bader
- Klinikum Bielefeld Mitte, Zentrum für Frauenheilkunde, Bielefeld, Germany
| | | | | | | | | | | | - Doris Mayr
- LMU München, Pathologisches Institut, München, Germany
| | - Michael Kreißl
- Universität Magdeburg, Medizinische Fakultät, Universitätsklinik für Radiologie und Nuklearmedizin, Germany
| | - Katja Lindel
- Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
| | - Alexander Mustea
- Universitätsklinikum Bonn, Zentrum Gynäkologie und gynäkologische Onkologie, Bonn, Germany
| | - Vratislav Strnad
- Universitätsklinikum Erlangen, Brustzentrum Franken, Erlangen, Germany
| | - Ute Goerling
- Universitätsmedizin Berlin, Campus Charité Mitte, Charité Comprehensive Cancer Center, Berlin, Germany
| | - Gerd J. Bauerschmitz
- Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
| | - Jan Langrehr
- Martin-Luther-Krankenhaus, Klinik für Allgemein-, Gefäß- und Viszeralchirurgie, Berlin, Germany
| | - Joseph Neulen
- Uniklinik RWTH Aachen, Klinik für Gynäkologische Endokrinologie und Reproduktionsmedizin, Aachen, Germany
| | - Uwe Andreas Ulrich
- Martin-Luther-Krankenhaus, Johannesstift Diakonie, Gynäkologie, Berlin, Germany
| | | | | | - Markus Follmann
- Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
| | - Thomas Langer
- Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
| | - Gregor Wenzel
- Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
| | - Sylvia Weber
- Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
| | - Saskia Erdogan
- Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
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8
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Khallouki F, Hajji L, Saber S, Bouddine T, Edderkaoui M, Bourhia M, Mir N, Lim A, El Midaoui A, Giesy JP, Aboul-Soud MAM, Silvente-Poirot S, Poirot M. An Update on Tamoxifen and the Chemo-Preventive Potential of Vitamin E in Breast Cancer Management. J Pers Med 2023; 13:jpm13050754. [PMID: 37240924 DOI: 10.3390/jpm13050754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 04/24/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
Breast cancer (BC) is the most common female cancer in terms of incidence and mortality worldwide. Tamoxifen (Nolvadex) is a widely prescribed, oral anti-estrogen drug for the hormonal treatment of estrogen-receptor-positive BC, which represents 70% of all BC subtypes. This review assesses the current knowledge on the molecular pharmacology of tamoxifen in terms of its anticancer and chemo-preventive actions. Due to the importance of vitamin E compounds, which are widely taken as a supplementary dietary component, the review focuses only on the potential importance of vitamin E in BC chemo-prevention. The chemo-preventive and onco-protective effects of tamoxifen combined with the potential effects of vitamin E can alter the anticancer actions of tamoxifen. Therefore, methods involving an individually designed, nutritional intervention for patients with BC warrant further consideration. These data are of great importance for tamoxifen chemo-prevention strategies in future epidemiological studies.
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Affiliation(s)
- Farid Khallouki
- Biology Department, FSTE, Moulay Ismail University of Meknes, BP 609, Errachidia 52000, Morocco
- Biology Department, Faculty of Sciences, Moulay Ismail University of Meknes, BP. 11201 Zitoune, Meknes 50050, Morocco
| | - Lhoussain Hajji
- Biology Department, Faculty of Sciences, Moulay Ismail University of Meknes, BP. 11201 Zitoune, Meknes 50050, Morocco
| | - Somayya Saber
- Biology Department, FSTE, Moulay Ismail University of Meknes, BP 609, Errachidia 52000, Morocco
- Biology Department, Faculty of Sciences, Moulay Ismail University of Meknes, BP. 11201 Zitoune, Meknes 50050, Morocco
| | - Toufik Bouddine
- Biology Department, Faculty of Sciences, Moulay Ismail University of Meknes, BP. 11201 Zitoune, Meknes 50050, Morocco
| | - Mouad Edderkaoui
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center & University of California, Los Angeles, CA 90048, USA
| | - Mohammed Bourhia
- Higher Institute of Nursing Professions and Technical Health, Laayoune 70000, Morocco
| | - Nora Mir
- Biology Department, Faculty of Sciences, Moulay Ismail University of Meknes, BP. 11201 Zitoune, Meknes 50050, Morocco
| | - Adrian Lim
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center & University of California, Los Angeles, CA 90048, USA
| | - Adil El Midaoui
- Biology Department, FSTE, Moulay Ismail University of Meknes, BP 609, Errachidia 52000, Morocco
| | - John P Giesy
- Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada
- Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
- Department of Integrative Biology, Michigan State University, East Lansing, MI 48824, USA
- Department of Environmental Sciences, Baylor University, Waco, TX 76706, USA
| | - Mourad A M Aboul-Soud
- Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia
| | - Sandrine Silvente-Poirot
- Cancer Research Center of Toulouse, UMR 1037 INSERM, UMR 5071 CNRS, University of Toulouse III, Equipe labellisée par la Ligue Nationale Contre le Cancer, 31037 Toulouse, France
- French Network for Nutrition And Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France
| | - Marc Poirot
- Cancer Research Center of Toulouse, UMR 1037 INSERM, UMR 5071 CNRS, University of Toulouse III, Equipe labellisée par la Ligue Nationale Contre le Cancer, 31037 Toulouse, France
- French Network for Nutrition And Cancer Research (NACRe Network), 78350 Jouy-en-Josas, France
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9
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Alfaris I, Asselah J, Aziz H, Bouganim N, Mousavi N. The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer. Curr Atheroscler Rep 2023; 25:145-154. [PMID: 36848014 DOI: 10.1007/s11883-023-01085-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/22/2023] [Indexed: 03/01/2023]
Abstract
PURPOSE OF REVIEW Cardiovascular disease accounts for up to 10% of all-cause mortality in women with a diagnosis of breast cancer, and the causes for this are multifaceted. Many women at risk of or with a diagnosis of breast cancer are on endocrine-modulating therapies. It is therefore important to understand the effect of hormone therapies on cardiovascular outcomes in breast cancer patients to mitigate against any adverse effects and to identify those most at risk so that they can be proactively managed. Here we discuss the pathophysiology of these agents, their effect on the cardiovascular system, and the latest evidence on their cardiovascular risks association. RECENT FINDINGS Tamoxifen appears to be cardioprotective during treatment but not over the longer term, while the effect of AIs on cardiovascular outcomes remains controversial. Heart failure outcomes remain understudied, and the cardiovascular effects of gonadotrophin-releasing hormone agonists (GNRHa) in women need further research, especially since data from men with prostate cancer have indicated an increased risk of cardiac events in GNRHa users. There remains a need for a greater understanding of the effects of hormone therapies on cardiovascular outcomes in breast cancer patients. Further areas of research in this area include developing evidence to better define the optimal preventive and screening methods for cardiovascular effects and the risk factors for patients on hormonal therapies.
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Affiliation(s)
- Ibrahim Alfaris
- Division of Cardiology, Department of Medicine, McGill University Health Center, Montreal, Canada.
| | - Jamil Asselah
- Department of Oncology, McGill University Health Center, Montreal, Canada
| | - Haya Aziz
- Division of Cardiology, Department of Medicine, McGill University Health Center, Montreal, Canada
| | - Nathaniel Bouganim
- Department of Oncology, McGill University Health Center, Montreal, Canada
| | - Negareh Mousavi
- Division of Cardiology, Department of Medicine, McGill University Health Center, Montreal, Canada
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10
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Kwolek DG, Gerstberger S, Tait S, Qiu JM. Ovarian, Uterine, and Vulvovaginal Cancers: Screening, Treatment Overview, and Prognosis. Med Clin North Am 2023; 107:329-355. [PMID: 36759101 DOI: 10.1016/j.mcna.2022.10.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Ovarian, uterine, and vulvovaginal cancers affect approximately 96,000 women per year in the United States, resulting in approximately 29,000 deaths annually. Routine screening protocols do not detect these malignancies; thus, the recognition of risk factors and evaluation of worrisome symptoms are essential for early detection and improved prognoses. Treatment is managed by gynecologic oncologists, and often involves a combination of surgery, chemotherapy, and possible radiation treatments. Survivor care is managed by the primary-care clinician: expert attention to the mental, physical, and sexual health of each patient will ensure the best outcomes and quality of life.
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Affiliation(s)
- Deborah Gomez Kwolek
- Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
| | - Stefanie Gerstberger
- Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - Sarah Tait
- Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
| | - Jeanna M Qiu
- Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
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11
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The neuroprotective effects of estrogen and estrogenic compounds in spinal cord injury. Neurosci Biobehav Rev 2023; 146:105074. [PMID: 36736846 DOI: 10.1016/j.neubiorev.2023.105074] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 01/29/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023]
Abstract
Spinal cord injury (SCI) occurs when the spinal cord is damaged from either a traumatic event or disease. SCI is characterised by multiple injury phases that affect the transmission of sensory and motor signals and lead to temporary or long-term functional deficits. There are few treatments for SCI. Estrogens and estrogenic compounds, however, may effectively mitigate the effects of SCI and therefore represent viable treatment options. This review systematically examines the pre-clinical literature on estrogen and estrogenic compound neuroprotection after SCI. Several estrogens were examined by the included studies: estrogen, estradiol benzoate, Premarin, isopsoralen, genistein, and selective estrogen receptor modulators. Across these pharmacotherapies, we find significant evidence that estrogens indeed offer protection against myriad pathophysiological effects of SCI and lead to improvements in functional outcomes, including locomotion. A STRING functional network analysis of proteins modulated by estrogen after SCI demonstrated that estrogen simultaneously upregulates known neuroprotective pathways, such as HIF-1, and downregulates pro-inflammatory pathways, including IL-17. These findings highlight the strong therapeutic potential of estrogen and estrogenic compounds after SCI.
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12
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Kim D, Oh J, Seok JH, Lee HS, Jeon S, Yoon CI. Risk of Secondary Cancer after Adjuvant Tamoxifen Treatment for Ductal Carcinoma In Situ: A Nationwide Cohort Study in South Korea. Diagnostics (Basel) 2023; 13:diagnostics13040792. [PMID: 36832280 PMCID: PMC9954831 DOI: 10.3390/diagnostics13040792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/05/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Endocrine therapy is the mainstay treatment for hormone receptor-positive ductal carcinoma in situ. The aim of this study was to examine the long-term secondary malignancy risk of tamoxifen therapy. The data of patients diagnosed with breast cancer between January 2007 and December 2015 were retrieved from the database of the Health Insurance Review and Assessment Service of South Korea. The International Classification of Diseases, 10th revision, was used to track all-site cancers. Age at the time of surgery, chronic disease status, and type of surgery were considered covariates in the propensity score matching analysis. The median follow-up duration was 89 months. Forty-one patients in the tamoxifen group and nine in the control group developed endometrial cancer. The Cox regression hazard ratio model showed that tamoxifen therapy was the only significant predictor of the development of endometrial cancer (hazard ratio, 2.791; 95% confidence interval, 1.355-5.747; p = 0.0054). No other type of cancer was associated with long-term tamoxifen use. In consonance with the established knowledge, the real-world data in this study demonstrated that tamoxifen therapy is related to an increased incidence of endometrial cancer.
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Affiliation(s)
- Dooreh Kim
- Division of Breast Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Jooyoung Oh
- Department of Psychiatry, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jeong-Ho Seok
- Department of Psychiatry, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Soyoung Jeon
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Chang Ik Yoon
- Division of Breast Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
- Correspondence: ; Tel.: +82-2-2258-6109
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13
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Suba Z. Rosetta Stone for Cancer Cure: Comparison of the Anticancer Capacity of Endogenous Estrogens, Synthetic Estrogens and Antiestrogens. Oncol Rev 2023; 17:10708. [PMID: 37152665 PMCID: PMC10154579 DOI: 10.3389/or.2023.10708] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 03/30/2023] [Indexed: 05/09/2023] Open
Abstract
This work presents the history of the recognition of principal regulatory capacities of estrogen hormones having been mistakenly regarded as breast cancer promoting agents for more than 120 years. Comprehensive analysis of the results of clinical, epidemiological, immunological and molecular studies justified that endogenous estrogens are the principal regulators of embryonic development, survival and reproduction via orchestrating appropriate expression and even edition of all genes in mammalians. Medical use of chemically modified synthetic estrogens caused toxic complications; thromboembolic events and increased cancer risk in female organs as they proved to be endocrine disruptors deregulating estrogen receptors (ERs) rather than their activators. Synthetic estrogen treatment exhibits ambiguous correlations with cancer risk at different sites, which may be attributed to an inhibition of the unliganded activation of estrogen receptors (ERs) coupled with compensatory liganded activation. The principle of estrogen induced breast cancer led to the introduction of antiestrogen therapies against this tumor; inhibition of the liganded activation of estrogen receptors and aromatase enzyme activity. The initial enthusiasm turned into disappointment as the majority of breast cancers proved to be primarily resistant to antiestrogens. In addition, nearly all patients showing earlier good tumor responses to endocrine therapy, later experienced secondary resistance leading to metastatic disease and fatal outcome. Studying the molecular events in tumors responsive and unresponsive to antiestrogen therapy, it was illuminated that a complete inhibition of liganded ER activation stimulates the growth of cancers, while a successful compensatory upregulation of estrogen signal may achieve DNA restoration, tumor regression and patient's survival. Recognition of the principal role of endogenous estrogens in gene expression, gene edition and DNA repair, estrogen treatment and stimulation of ER expression in patients may bring about a great turn in medical practice.
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14
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Simek S, Lue B, Rao A, Ravipati G, Vallabhaneni S, Zhang K, Zaha VG, Chandra A. Gender Differences in Diagnosis, Prevention, and Treatment of Cardiotoxicity in Cardio-Oncology. J Clin Med 2022; 11:jcm11175167. [PMID: 36079097 PMCID: PMC9457034 DOI: 10.3390/jcm11175167] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/23/2022] [Accepted: 08/30/2022] [Indexed: 12/04/2022] Open
Abstract
Gender differences exist throughout the medical field and significant progress has been made in understanding the effects of gender in many aspects of healthcare. The field of cardio-oncology is diverse and dynamic with new oncologic and cardiovascular therapies approved each year; however, there is limited knowledge regarding the effects of gender within cardio-oncology, particularly the impact of gender on cardiotoxicities. The relationship between gender and cardio-oncology is unique in that gender likely affects not only the biological underpinnings of cancer susceptibility, but also the response to both oncologic and cardiovascular therapies. Furthermore, gender has significant socioeconomic and psychosocial implications which may impact cancer and cardiovascular risk factor profiles, cancer susceptibility, and the delivery of healthcare. In this review, we summarize the effects of gender on susceptibility of cancer, response to cardiovascular and cancer therapies, delivery of healthcare, and highlight the need for further gender specific studies regarding the cardiovascular effects of current and future oncological treatments.
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Affiliation(s)
- Shawn Simek
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Correspondence: (S.S.); (A.C.); Tel.: +1-214-645-7514 (A.C.)
| | - Brian Lue
- UT Southwestern Medical School, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Anjali Rao
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Goutham Ravipati
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Srilakshmi Vallabhaneni
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Cardio-Oncology Program, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Kathleen Zhang
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Cardio-Oncology Program, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Vlad G. Zaha
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Cardio-Oncology Program, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Alvin Chandra
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Cardio-Oncology Program, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Correspondence: (S.S.); (A.C.); Tel.: +1-214-645-7514 (A.C.)
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15
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Gupta T, Purington N, Liu M, Han S, Sledge G, Schapira L, Kurian AW. Incident comorbidities after tamoxifen or aromatase inhibitor therapy in a racially and ethnically diverse cohort of women with breast cancer. Breast Cancer Res Treat 2022; 196:175-183. [DOI: 10.1007/s10549-022-06716-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/14/2022] [Indexed: 11/29/2022]
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16
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Bergler-Klein J, Rainer PP, Wallner M, Zaruba MM, Dörler J, Böhmer A, Buchacher T, Frey M, Adlbrecht C, Bartsch R, Gyöngyösi M, Fürst UM. Cardio-oncology in Austria: cardiotoxicity and surveillance of anti-cancer therapies : Position paper of the Heart Failure Working Group of the Austrian Society of Cardiology. Wien Klin Wochenschr 2022; 134:654-674. [PMID: 35507087 PMCID: PMC9065248 DOI: 10.1007/s00508-022-02031-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 03/18/2022] [Indexed: 02/07/2023]
Abstract
Survival in cancer is continuously improving due to evolving oncological treatment. Therefore, cardiovascular short-term and long-term side effects gain crucial importance for overall outcome. Cardiotoxicity not only presents as heart failure, but also as treatment-resistant hypertension, acute coronary ischemia with plaque rupture or vasospasm, thromboembolism, arrhythmia, pulmonary hypertension, diastolic dysfunction, acute myocarditis and others. Recent recommendations have proposed baseline cardiac risk assessment and surveillance strategies. Major challenges are the availability of monitoring and imaging resources, including echocardiography with speckle tracking longitudinal strain (GLS), serum biomarkers such as natriuretic peptides (NT-proBNP) and highly sensitive cardiac troponins. This Austrian consensus encompasses cardiotoxicity occurrence in frequent antiproliferative cancer drugs, radiotherapy, immune checkpoint inhibitors and cardiac follow-up considerations in cancer survivors in the context of the Austrian healthcare setting. It is important to optimize cardiovascular risk factors and pre-existing cardiac diseases without delaying oncological treatment. If left ventricular ejection fraction (LVEF) deteriorates during cancer treatment (from >10% to <50%), or myocardial strain decreases (>15% change in GLS), early initiation of cardioprotective therapies (angiotensin-converting enzyme inhibitors, angiotensin or beta receptor blockers) is recommended, and LVEF should be reassessed before discontinuation. Lower LVEF cut-offs were recently shown to be feasible in breast cancer patients to enable optimal anticancer treatment. Interdisciplinary cardio-oncology cooperation is pivotal for optimal management of cancer patients.
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Affiliation(s)
- Jutta Bergler-Klein
- Department of Cardiology, University Clinic of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
| | - Peter P Rainer
- Division of Cardiology, Medical University of Graz, Graz, Austria.,BioTechMed Graz, Graz, Austria
| | - Markus Wallner
- Division of Cardiology, Medical University of Graz, Graz, Austria.,Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Marc-Michael Zaruba
- Department of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Jakob Dörler
- Department of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria.,Department of Internal Medicine and Cardiology, Klinikum Klagenfurt, Klagenfurt, Austria
| | - Armin Böhmer
- Department of Internal Medicine 1, Krems University Clinic, Krems, Austria
| | - Tamara Buchacher
- Department of Internal Medicine and Cardiology, Klinikum Klagenfurt, Klagenfurt, Austria
| | - Maria Frey
- Department of Cardiology, University Clinic of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | | | - Rupert Bartsch
- Department of Medicine 1, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Mariann Gyöngyösi
- Department of Cardiology, University Clinic of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Ursula-Maria Fürst
- Department of Internal Medicine, Hospital of the Brothers of St. John of God (Krankenhaus Barmherzige Brüder) Salzburg, Salzburg, Austria
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17
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Saccardi C, Spagnol G, Bonaldo G, Marchetti M, Tozzi R, Noventa M. New Light on Endometrial Thickness as a Risk Factor of Cancer: What Do Clinicians Need to Know? Cancer Manag Res 2022; 14:1331-1340. [PMID: 35401014 PMCID: PMC8985823 DOI: 10.2147/cmar.s294074] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 03/21/2022] [Indexed: 12/21/2022] Open
Abstract
Transvaginal ultrasound (TVUS) represents an accurate and noninvasive technique to investigate endometrial thickness (ET) in the early diagnosis of endometrial cancer (EC). In the literature, for maximum ET there is no consensus on the cutoff value for normal ET in postmenopause for either symptomatic or asymptomatic women. Most patients with EC present with postmenopausal bleeding (PMB) and in these patients is necessary to perform TVUS to evaluate ET as an indicator for endometrial biopsy. On the contrary, if ET is incidentally detected in postmenopausal patients without bleeding, endometrial sampling for a postmenopausal woman without bleeding should not be routinely performed, although it is estimated that up to 15% of EC occurs in women without vaginal bleeding. The aim of our review was to give clinicians necessary and useful knowledge on the role of TVUS and ET for early detection of EC in their daily routine practice. Based on the most important studies in the literature, we summarized that in premenopausal woman with abnormal uterine bleeding, an optimal cutoff for ET has not yet been established. For postmenopausal women with PMB, at low risk, and ET <4 mm, a follow-up scan could be offered, and for women with ET ≥4 mm, office hysteroscopy-guided endometrial sampling is recommended independently of ET results. On the other hand, in postmenopausal women with PMB and at high risk of EC, office hysteroscopy-guided endometrial sampling is necessary. In postmenopausal women without PMB and ET ≥4 mm, arbitrary endometrial sampling is not recommended, but evaluated case by case based on risk factors. In conclusion, there is broad consensus on the importance of TVUS and the need for further investigation based on risk factors of EC.
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Affiliation(s)
- Carlo Saccardi
- Department of Women and Children’s Health, University of Padua, Padua, Italy
| | - Giulia Spagnol
- Department of Women and Children’s Health, University of Padua, Padua, Italy
| | - Giulio Bonaldo
- Department of Women and Children’s Health, University of Padua, Padua, Italy
| | - Matteo Marchetti
- Department of Women and Children’s Health, University of Padua, Padua, Italy
| | - Roberto Tozzi
- Department of Women and Children’s Health, University of Padua, Padua, Italy
| | - Marco Noventa
- Department of Women and Children’s Health, University of Padua, Padua, Italy
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18
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Yu Q, Xu Y, Yu E, Zheng Z. Risk of cardiovascular disease in breast cancer patients receiving aromatase inhibitors vs. tamoxifen: A systematic review and meta-analysis. J Clin Pharm Ther 2022; 47:575-587. [PMID: 34984740 DOI: 10.1111/jcpt.13598] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 12/13/2021] [Accepted: 12/23/2021] [Indexed: 01/10/2023]
Abstract
WHAT IS KNOWN AND OBJECTIVE Breast cancer is one of the leading causes of morbidity and mortality in women worldwide. In order to reduce the risks of its recurrence, endocrine therapies, such as tamoxifen and aromatase inhibitors are commonly administered. Despite having a similar efficacy in preventing breast cancer recurrence, these drugs differ in terms of instigating cardiovascular morbidities. Recent randomized controlled trials and cohort studies provide inconclusive evidence of the cardiovascular risks associated with the administration of these endocrine therapies. This present review and meta-analysis evaluates the comparative cardiovascular adverse event outcomes in breast cancer patients receiving tamoxifen and aromatase inhibitors. To evaluate the comparative cardiovascular adverse outcomes, such as venous thromboembolism, heart failure, angina, myocardial infarction and stroke in patients with breast cancer receiving tamoxifen and aromatase inhibitors. METHODS A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases, including Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE. A random-effect meta-analysis was conducted to compare the cardiovascular adverse events (i.e. venous thromboembolism, heart failure, angina, myocardial infarction, stroke) in breast cancer patients treated with tamoxifen and aromatase inhibitors. RESULTS AND DISCUSSION From 993 studies, 20 eligible studies were identified, with 174,142 female breast cancer patients (mean age: 67.4 ± 3.8 years). A meta-analysis revealed insignificantly (p > 0.05) higher risks of venous thromboembolism (Odds ratio, 95% CI: 1.70, 0.91-3.18) in patients treated with tamoxifen as compared to aromatase inhibitors. We also observed insignificantly higher risks of stroke (0.93, 0.45-1.91), angina (0.77, 0.12-4.59), myocardial infarction (0.74, 0.30-1.79), and heart failure (0.81, 0.22-2.91) in patients receiving aromatase inhibitors as compared to tamoxifen. WHAT IS NEW AND CONCLUSIONS The study provides evidence regarding the comparative cardiovascular adverse outcomes between breast cancer patients consuming tamoxifen and aromatase inhibitors. The study reports an insignificant increase in the events of stroke, angina, myocardial infarction, and heart failure in breast cancer patients treated with aromatase inhibitors as compared to tamoxifen. The study also reports that tamoxifen treatment is associated with an insignificant increase in the events of venous thromboembolism as compared to treatment with aromatase inhibitors.
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Affiliation(s)
- Qiuyan Yu
- Department of Nursing, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China
| | - Yueping Xu
- Department of Nursing, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China
| | - Enguang Yu
- Department of Nursing, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China
| | - Zhufeng Zheng
- Department of Nursing, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China
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19
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Singh P, Covassin N, Marlatt K, Gadde KM, Heymsfield SB. Obesity, Body Composition, and Sex Hormones: Implications for Cardiovascular Risk. Compr Physiol 2021; 12:2949-2993. [PMID: 34964120 PMCID: PMC10068688 DOI: 10.1002/cphy.c210014] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Cardiovascular disease (CVD) continues to be the leading cause of death in adults, highlighting the need to develop novel strategies to mitigate cardiovascular risk. The advancing obesity epidemic is now threatening the gains in CVD risk reduction brought about by contemporary pharmaceutical and surgical interventions. There are sex differences in the development and outcomes of CVD; premenopausal women have significantly lower CVD risk than men of the same age, but women lose this advantage as they transition to menopause, an observation suggesting potential role of sex hormones in determining CVD risk. Clear differences in obesity and regional fat distribution among men and women also exist. While men have relatively high fat in the abdominal area, women tend to distribute a larger proportion of their fat in the lower body. Considering that regional body fat distribution is an important CVD risk factor, differences in how men and women store their body fat may partly contribute to sex-based alterations in CVD risk as well. This article presents findings related to the role of obesity and sex hormones in determining CVD risk. Evidence for the role of sex hormones in determining body composition in men and women is also presented. Lastly, the clinical potential for using sex hormones to alter body composition and reduce CVD risk is outlined. © 2022 American Physiological Society. Compr Physiol 12:1-45, 2022.
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Affiliation(s)
- Prachi Singh
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
| | | | - Kara Marlatt
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
| | - Kishore M Gadde
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
| | - Steven B Heymsfield
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
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20
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Finney CA, Shvetcov A, Westbrook RF, Morris MJ, Jones NM. Tamoxifen offers long-term neuroprotection after hippocampal silent infarct in male rats. Horm Behav 2021; 136:105085. [PMID: 34749277 DOI: 10.1016/j.yhbeh.2021.105085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 11/19/2022]
Abstract
Silent infarcts (SI) are a cerebral small vessel disease characterized by small subcortical infarcts. These occur in the absence of typical ischemia symptoms but are linked to cognitive decline and dementia. While there are no approved treatments for SI, recent results from our laboratory suggest that tamoxifen, a selective estrogen receptor modulator, is a viable candidate. In the present study, we induced SI in the dorsal hippocampal CA1 region of rats and assessed the effects of systemic administration of tamoxifen (5 mg/kg, twice) 21 days after injury on cognitive and pathophysiological measures, including cell loss, apoptosis, gliosis and estrogen receptors (ERs). We found that tamoxifen protected against the SI-induced cognitive dysfunction on the hippocampal-dependent, place recognition task, cell and ER loss, and increased apoptosis and gliosis in the CA1. Exploratory data analyses using a scatterplot matrix and principal component analysis indicated that SI-tamoxifen rats were indistinguishable from sham controls while they differed from SI rats, who were characterized by enhanced cell loss, apoptosis and gliosis, lower ERs, and recognition memory deficit. Supervised machine learning using support vector machine (SVM) determined predictors of progression from the early ischemic state to the dementia-like state. It showed that caspase-3 and ERα in the CA1 and exploration proportion were reliable and accurate predictors of this progression. Importantly, tamoxifen ameliorated SI-induced effects on all three of these variables, providing further evidence for its viability as a candidate treatment for SI and prevention of associated dementia.
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21
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Sütcüoğlu O, Yazıcı O, Özet A. Is it necessary to measure basal serum lipid levels in cancer patients prior to tamoxifen treatment? Future Oncol 2021; 17:4823-4825. [PMID: 34672686 DOI: 10.2217/fon-2021-1107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Osman Sütcüoğlu
- Gazi University, Department of Medical Oncology, Ankara, Turkey
| | - Ozan Yazıcı
- Gazi University, Department of Medical Oncology, Ankara, Turkey
| | - Ahmet Özet
- Gazi University, Department of Medical Oncology, Ankara, Turkey
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22
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Chen NC, Liao KM, Tian YF, Wu YC, Wang JJ, Ho CH, Hsu CC. Risk of Stroke in Patients with Breast Cancer and Sleep Disorders. J Cancer 2021; 12:6749-6755. [PMID: 34659564 PMCID: PMC8518003 DOI: 10.7150/jca.63184] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/22/2021] [Indexed: 12/24/2022] Open
Abstract
Breast cancer and stroke were leading cause of cancer-related mortality in the world. Stroke is the second leading cause of death. Previous studies showed that patients with breast cancer had a relatively higher risk of sleep disorders. Sleep disorders increased the risk of stroke. The aim of our study was to examine the risk of stroke after a breast cancer with sleep disorder among women in Taiwan. The Taiwan Cancer Registry was used to identify patients with breast cancer. Patients with new-onset breast cancer from January 2007 to December 2015 were selected for this study and followed until December 31, 2017. Patients who were diagnosed with sleep disorders were set as the case group, and the controls were those without sleep disorders. We enrolled 5256 patients with sleep disorders and 10,512 patients without sleep disorders. There were 121 (2.30%) patients with ischemic stroke among the breast cancer patients with sleep disorders. The mean time from the diagnosis of breast cancer to the occurrence of ischemic stroke was 6.29±2.59 years for breast cancer patients with sleep disorders and 6.00±2.76 years for those without sleep disorders (p < 0.0001). After matching by age and index year, breast patients with sleep disorders had a 1.31-fold higher risk (95% confidence interval: 1.03-1.66; p-value=0.026) of ischemic stroke than those without sleep disorders, after adjustment for comorbidities, cancer clinical stage, and treatment types. In conclusion, Breast cancer patients with sleep disorders have an increased risk of stroke.
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Affiliation(s)
- Nan-Cheng Chen
- Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan.,Department of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Kuang-Ming Liao
- Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan
| | - Yu-Feng Tian
- Division of Gastroenterology & General Surgery, Chi Mei Medical Center, Tainan, Taiwan.,Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Yu-Cih Wu
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Jhi-Joung Wang
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.,Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan
| | - Chung-Han Ho
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.,Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan.,Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chien-Chin Hsu
- Department of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.,Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan
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23
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Rivier C, Mery B, Rowinski E, Sotton S, Bouleftour W, Bertoletti L, Tredan O, Magne N. Breast cancer treatment-related cardiovascular disturbances: advocacy for a watchful attitude in this never-ending story. Expert Opin Drug Saf 2021; 21:453-465. [PMID: 34551666 DOI: 10.1080/14740338.2021.1983541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Thanks to the emergence of new therapeutics, prognosis and outcome of breast cancer patients (any subtype) have improved significantly. This raises the issue of the interactions and side effects related to the use of multiple drugs. Thus, to decide on a treatment, the optimal benefit risk-ratio should be carefully watched as toxicities such as cardiac ones effect on long-term survival. Indeed, nowadays in France, cardiovascular diseases rank first as causes of death in women. AREAS COVERED This non-exhaustive review aims to report the currently available data on cardiac side effects caused by the use of emerging drugs in breast cancer, in localized or metastatic diseases alike. We will focus on HER2-inhibitors, cyclin-dependent-kinase 4/6 and PARP inhibitors, chemotherapy and immunotherapy, before discussing the means of prevention. EXPERT OPINION Although this issue has largely been studied, the recent emergence of new drugs emphasizes the necessity for oncologists to adapt their practice to a multidisciplinary model that includes cardio-oncology.
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Affiliation(s)
- Charlène Rivier
- Department of Medical Oncology, Lucien Neuwirth Cancer Centre, Saint Priest En Jarez, France
| | - Benoite Mery
- Department of Medical Oncology, Léon Bérard Cancer Centre, Lyon, France
| | - Elise Rowinski
- Department of Medical Oncology, Lucien Neuwirth Cancer Centre, Saint Priest En Jarez, France
| | - Sandrine Sotton
- Department of Research and Teaching in Oncology, Lucien Neuwirth Cancer Centre, Saint Priest En Jarez, France
| | - Wafa Bouleftour
- Department of Research and Teaching in Oncology, Lucien Neuwirth Cancer Centre, Saint Priest En Jarez, France
| | - Laurent Bertoletti
- Department on Vascular Medicine, Saint-Etienne Teaching Hospital (Chu), Saint-Etienne, France.,INSERM, UMR 1059, Saint-Etienne University, Saint-Etienne, France.,INSER, CIC-1408, Saint-Etienne Teaching Hospital (CHU), Saint-Etienne, France
| | - Olivier Tredan
- Department of Medical Oncology, Léon Bérard Cancer Centre, Lyon, France
| | - Nicolas Magne
- Department of Research and Teaching in Oncology, Lucien Neuwirth Cancer Centre, Saint Priest En Jarez, France.,Department of Radiation Oncology, Lucien Neuwirth Cancer Centre, Saint Priest En Jarez, France
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24
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Burguin A, Diorio C, Durocher F. Breast Cancer Treatments: Updates and New Challenges. J Pers Med 2021; 11:808. [PMID: 34442452 PMCID: PMC8399130 DOI: 10.3390/jpm11080808] [Citation(s) in RCA: 195] [Impact Index Per Article: 48.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/09/2021] [Accepted: 08/16/2021] [Indexed: 12/31/2022] Open
Abstract
Breast cancer (BC) is the most frequent cancer diagnosed in women worldwide. This heterogeneous disease can be classified into four molecular subtypes (luminal A, luminal B, HER2 and triple-negative breast cancer (TNBC)) according to the expression of the estrogen receptor (ER) and the progesterone receptor (PR), and the overexpression of the human epidermal growth factor receptor 2 (HER2). Current BC treatments target these receptors (endocrine and anti-HER2 therapies) as a personalized treatment. Along with chemotherapy and radiotherapy, these therapies can have severe adverse effects and patients can develop resistance to these agents. Moreover, TNBC do not have standardized treatments. Hence, a deeper understanding of the development of new treatments that are more specific and effective in treating each BC subgroup is key. New approaches have recently emerged such as immunotherapy, conjugated antibodies, and targeting other metabolic pathways. This review summarizes current BC treatments and explores the new treatment strategies from a personalized therapy perspective and the resulting challenges.
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Affiliation(s)
- Anna Burguin
- Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1T 1C2, Canada;
- Cancer Research Center, CHU de Québec-Université Laval, Quebec City, QC G1V 4G2, Canada;
| | - Caroline Diorio
- Cancer Research Center, CHU de Québec-Université Laval, Quebec City, QC G1V 4G2, Canada;
- Department of Preventive and Social Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1T 1C2, Canada
| | - Francine Durocher
- Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1T 1C2, Canada;
- Cancer Research Center, CHU de Québec-Université Laval, Quebec City, QC G1V 4G2, Canada;
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25
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Finney CA, Shvetcov A, Westbrook RF, Morris MJ, Jones NM. The selective estrogen receptor modulator tamoxifen protects against subtle cognitive decline and early markers of injury 24 h after hippocampal silent infarct in male Sprague-Dawley rats. Horm Behav 2021; 134:105016. [PMID: 34242875 DOI: 10.1016/j.yhbeh.2021.105016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 06/03/2021] [Accepted: 06/05/2021] [Indexed: 02/07/2023]
Abstract
Silent infarcts (SI) are subcortical cerebral infarcts occurring in the absence of typical ischemia symptoms and are linked to cognitive decline and dementia development. There are no approved treatments for SI. One potential treatment is tamoxifen, a selective estrogen receptor modulator. It is critical to establish whether treatments effectively target the early consequences of SI to avoid progression to complete injury. We induced SI in the dorsal hippocampal CA1 of rats and assessed whether tamoxifen is protective 24 h later against cognitive deficits and injury responses including gliosis, apoptosis, inflammation and changes in estrogen receptors (ERs). SI led to subtle cognitive impairment on the object place task, an effect ameliorated by tamoxifen administration. SI did not lead to detectable hippocampal cell loss but increased apoptosis, astrogliosis, microgliosis and inflammation. Tamoxifen protected against the effects of SI on all measures except microgliosis. SI increased ERα and decreased ERβ in the hippocampus, which were mitigated by tamoxifen. Exploratory data analyses using scatterplot matrices and principal component analysis indicated that SI rats given tamoxifen were indistinguishable from controls. Further, SI rats were significantly different from all other groups, an effect associated with low levels of ERα and increased apoptosis, gliosis, inflammation, ERβ, and time spent with the unmoved object. The results demonstrate that tamoxifen is protective against the early cellular and cognitive consequences of hippocampal SI 24 h after injury. Tamoxifen mitigates apoptosis, gliosis, and inflammation and normalization of ER levels in the CA1, leading to improved cognitive outcomes after hippocampal SI.
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26
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Isobe H, Shimoda M, Kan Y, Tatsumi F, Katakura Y, Kimura T, Obata A, Kohara K, Nakanishi S, Mune T, Kaku K, Kaneto H. A case of tamoxifen-induced hypertriglyceridemia monitoring the changes in lipoprotein fractions over time. BMC Endocr Disord 2021; 21:115. [PMID: 34107939 PMCID: PMC8191117 DOI: 10.1186/s12902-021-00780-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 06/01/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Tamoxifen, which is one of the selective estrogen receptor modulators (SERMs), can bring out life-threatening complication, e.g. hypertriglyceridemia-induced acute pancreatitis, although it is rare. We precisely report changes in lipoprotein metabolism before and after tamoxifen discontinuation because there have been few reports of it. CASE PRESENTATION 47-year-old premenopausal woman with dyslipidemia, type 2 diabetes, nonalcoholic fatty liver disease and chronic kidney disease was prescribed tamoxifen as adjuvant therapy after operation of breast cancer. She experienced severe tamoxifen-induced hypertriglyceridemia several months after dosing tamoxifen. Before cessation of tamoxifen, lipoprotein fraction test revealed marked stagnation of VLDL and IDL metabolisms, resulting in severe hypertriglyceridemia (serum triglyceride level was 1881 mg/dL). Seven days after tamoxifen withdrawal, lipoprotein fraction test showed that the metabolisms of endogenous lipoproteins were changed drastically. CONCLUSIONS From these results, we confirmed that tamoxifen certainly changes lipoprotein metabolism through suppression of post-heparin lipolytic activity. It is very important to evaluate the balance between benefit and risk before dosing tamoxifen and survey lipid profiles constantly during treatment to avoid life-threatening complication when prescription of tamoxifen is planned.
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Affiliation(s)
- Hayato Isobe
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Masashi Shimoda
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan.
| | - Yuki Kan
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Fuminori Tatsumi
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Yukino Katakura
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Tomohiko Kimura
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Atsushi Obata
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Kenji Kohara
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Shuhei Nakanishi
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Tomoatsu Mune
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Kohei Kaku
- Professor with special assignment, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Hideaki Kaneto
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
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27
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Okwuosa TM, Morgans A, Rhee JW, Reding KW, Maliski S, Plana JC, Volgman AS, Moseley KF, Porter CB, Ismail-Khan R. Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association. CIRCULATION-GENOMIC AND PRECISION MEDICINE 2021; 14:e000082. [PMID: 33896190 DOI: 10.1161/hcg.0000000000000082] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Cardiovascular disease and cancer are the leading causes of death in the United States, and hormone-dependent cancers (breast and prostate cancer) are the most common noncutaneous malignancies in women and men, respectively. The hormonal (endocrine-related) therapies that serve as a backbone for treatment of both cancers improve survival but also increase cardiovascular morbidity and mortality among survivors. This consensus statement describes the risks associated with specific hormonal therapies used to treat breast and prostate cancer and provides an evidence-based approach to prevent and detect adverse cardiovascular outcomes. Areas of uncertainty are highlighted, including the cardiovascular effects of different durations of hormonal therapy, the cardiovascular risks associated with combinations of newer generations of more intensive hormonal treatments, and the specific cardiovascular risks that affect individuals of various races/ethnicities. Finally, there is an emphasis on the use of a multidisciplinary approach to the implementation of lifestyle and pharmacological strategies for management and risk reduction both during and after active treatment.
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28
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Sun R, Chu Y, Gao Y, Cheng W, Gao S. Efficacy and safety of endocrine therapy for breast-cancer prevention in high-risk premenopausal or postmenopausal women: a Bayesian network meta-analysis of nine randomized controlled trials. Menopause 2021; 28:589-600. [PMID: 33857955 DOI: 10.1097/gme.0000000000001763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
IMPORTANCE Findings in this work might provide certain guidance for current clinical work. OBJECTIVE This study aimed to evaluate the efficacy and safety of these drugs based on the Bayesian network meta-analysis. EVIDENCE REVIEW Two researchers systematically and comprehensively searched PubMed, Embase, and the central databases of the Cochrane Library from inception to September 15, 2020. The number of specific events and sample size were extracted from each of the included studies. This Bayesian theory-based network meta-analysis included indirect comparisons and mixed treatment analysis. Indirect comparisons compare the efficacy of at least three interventions simultaneously and are mostly used when there are few direct comparison studies. In addition, indirect comparisons are conducted on the basis of direct comparisons through mixed treatment analysis, which can thus improve the accuracy of analysis. FINDINGS A total of nine randomized controlled trials involving 60,732 participants were included. As a result, compared with placebo in high-risk pre- or postmenopausal women, endocrine therapy (ET) decreased the risks of total breast cancer (TBC, odds ratio [OR] 0.69, 95% confidence interval [CI] 0.56-0.85), invasive breast cancer (IBC, OR 0.69, 95% CI 0.53-0.89), estrogen receptor-positive breast cancer (ER+BC) (OR 0.49, 95% CI 0.38-0.64), and ductal carcinoma in situ (OR 0.74, 95% CI 0.56-0.98), but increased the risks of pulmonary embolism (OR 1.33, 95% CI 1.05-1.69), total venous thrombosis (OR 1.75, 95% CI 1.28-2.38), and endometrial carcinoma (EC, OR 1.84, 95% CI 1.17-2.88). In further network stratification analyses, anastrozole, exemestane, and tamoxifen were found to decrease the risks of TBC, IBC, and ER + BC relative to placebo. Similarly, raloxifene decreased the risk of IBC (OR 0.65, 95% CI 0.48-0.85), while tamoxifen increased the risk of EC (OR 2.42, 95% CI 1.10-7.35). CONCLUSIONS AND RELEVANCE To sum up, ET decreased the risks of TBC, IBC, ER + BC, and ductal carcinoma in situ, while increasing the risks of pulmonary embolism, total venous thrombosis, and EC in high-risk pre- or postmenopausal women. Meanwhile, anastrozole, exemestane, and tamoxifen possibly exerted potential protective effects on TBC, IBC and ER + BC. Typically, raloxifene might be effective on IBC, while tamoxifen might increase the risk of EC. Therefore, clinicians should fully weigh the benefits and risks of ET to develop a rational individualized treatment.
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Affiliation(s)
- Rong Sun
- Department of Surgical Oncology, Affiliated Hospital of Qinghai University, Xining, China
| | - Yan Chu
- Department of Oncology, Affiliated Hospital of Jining Medical University, Zaozhuang Municipal Hospital, Zaozhuang, China
| | - Yan Gao
- Zaozhuang Vocational College Gucheng Campus, Shandong, China
| | - Wenke Cheng
- Department of Cardiology, Heart Center Leipzig at University Leipzig, Leipzig, Germany
| | - Shan Gao
- Department of Oncology, Affiliated Hospital of Jining Medical University, Zaozhuang Municipal Hospital, Zaozhuang, China
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29
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Noe JF, Bush MA. Endocrine Therapy for Breast Cancer. J Nurse Pract 2021. [DOI: 10.1016/j.nurpra.2020.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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30
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Khosrow-Khavar F, Bouganim N, Filion KB, Suissa S, Azoulay L. Cardiotoxicity of Use of Sequential Aromatase Inhibitors in Women With Breast Cancer. Am J Epidemiol 2020; 189:1086-1095. [PMID: 32338279 DOI: 10.1093/aje/kwaa065] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 04/15/2020] [Accepted: 04/17/2020] [Indexed: 12/22/2022] Open
Abstract
The association between use of aromatase inhibitors (AIs) and cardiovascular outcomes is controversial. While some observational studies have assessed the cardiovascular safety of AIs as upfront treatments, their cardiotoxicity as sequential treatments with tamoxifen remains unknown. Thus, we conducted a population-based cohort study using data from the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. We employed a prevalent new-user design to propensity-score match, in a 1:2 ratio, patients switching from tamoxifen to AIs with patients continuing tamoxifen between 1998 and 2016. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality). Overall, 1,962 patients switching to AIs were matched to 3,874 patients continuing tamoxifen. Compared with tamoxifen, AIs were associated with an increased risk of myocardial infarction (hazard ratio (HR) = 2.08, 95% confidence interval (CI): 1.02, 4.27). The hazard ratios were elevated for ischemic stroke (HR = 1.58, 95% CI: 0.85, 2.93) and heart failure (HR = 1.69, 95% CI: 0.79, 3.62) but not cardiovascular mortality (HR = 0.87, 95% CI: 0.49, 1.54), with confidence intervals including the null value. The elevated hazard ratios observed for the cardiovascular outcomes should be corroborated in future large observational studies.
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31
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Raičević V, Radulović N, Jovanović L, Rodić M, Kuzminac I, Jakimov D, Wrodnigg T, Knedel T, Janiak C, Sakač M. Ferrocenylmethylation of estrone and estradiol: Structure, electrochemistry, and antiproliferative activity of new ferrocene–steroid conjugates. Appl Organomet Chem 2020. [DOI: 10.1002/aoc.5889] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Vidak Raičević
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences University of Novi Sad Trg Dositeja Obradovića 3 Novi Sad 21000 Serbia
| | - Niko Radulović
- Department of Chemistry, Faculty of Sciences and Mathematics University of Niš Višegradska 33 Niš 18000 Serbia
| | - Ljiljana Jovanović
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences University of Novi Sad Trg Dositeja Obradovića 3 Novi Sad 21000 Serbia
| | - Marko Rodić
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences University of Novi Sad Trg Dositeja Obradovića 3 Novi Sad 21000 Serbia
| | - Ivana Kuzminac
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences University of Novi Sad Trg Dositeja Obradovića 3 Novi Sad 21000 Serbia
| | - Dimitar Jakimov
- Oncology Institute of Vojvodina Put doktora Goldmana 4 Sremska Kamenica 21204 Serbia
| | - Tanja Wrodnigg
- Glycogroup Institute of Chemistry and Technology of Biobased Systems, Graz University of Technology Stremayrgasse 9 Graz A‐8010 Austria
| | - Tim‐Oliver Knedel
- Institute for Inorganic Chemistry and Structural Chemistry Heinrich‐Heine‐Universität Düsseldorf, Universitätsstraße 1 Düsseldorf D‐40225 Germany
| | - Christoph Janiak
- Institute for Inorganic Chemistry and Structural Chemistry Heinrich‐Heine‐Universität Düsseldorf, Universitätsstraße 1 Düsseldorf D‐40225 Germany
| | - Marija Sakač
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences University of Novi Sad Trg Dositeja Obradovića 3 Novi Sad 21000 Serbia
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32
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Pathophysiology, Mechanism, and Outcome of Ischemic Stroke in Cancer Patients. J Stroke Cerebrovasc Dis 2020; 29:105299. [PMID: 32951960 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105299] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 08/31/2020] [Accepted: 09/01/2020] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES The purpose of this study is to assess the risk factors, biomarkers of stroke, mechanism, and outcomes of cerebral infarction among cancerous diseases. MATERIALS & METHODS 156 patients presented by acute ischemic stroke were divided into two groups: the first group included 78 ischemic stroke patients associated with different types of cancer and the second group (control group) included 78 ischemic stroke patients not associated with cancer. Both groups were compared regarding the risk factors, previous thrombotic activity, subtypes, biomarkers of stroke, and outcomes. RESULTS Cancer patients presented by acute ischemic stroke were accompanied by a significantly less incidence of diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease, and atrial fibrillation than non-cancer patients (P < 0.001). While, levels of biomarkers of inflammation like erythrocyte sedimentation rate and C-reactive protein, and stroke biomarkers like fibrinogen, and D-dimer, all together were highly elevated in cancerous disease group of patients (P < 0.01). The prevalence of deep vein thrombosis, pulmonary embolism, and myocardial infarction was significantly higher in patients with cancer than in control patients without cancer (P = 0.008, P < 0.01 and P < 0.01 respectively). The most common stroke etiologies were atherosclerosis of large arteries and stroke of undetermined cause in a cancerous group of patients. Cancer patients were accompanied by significant higher mortality rate (P = 0.005), and more disability as determined by mRS (P < 0.005) CONCLUSIONS: Pathophysiology and mechanism of ischemic stroke in cancerous disease patients were due to different risk factors, biomarkers of stroke, and subtypes in comparison with non- cancerous cases.
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Van Leeuwen MT, Luu S, Gurney H, Brown MR, Pearson SA, Webber K, Hunt L, Hong S, Delaney GP, Vajdic CM. Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews. JNCI Cancer Spectr 2020; 4:pkaa076. [PMID: 33392444 PMCID: PMC7768929 DOI: 10.1093/jncics/pkaa076] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 07/01/2020] [Accepted: 08/18/2020] [Indexed: 12/16/2022] Open
Abstract
Background Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesized systematically nor has the quality of evidence been considered. We synthesized systematic review evidence of cardiovascular toxicity of individual targeted agents. Methods We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for systematic reviews with meta-analyses of cardiovascular outcomes for individual agents published to May 2020. We selected reviews according to prespecified eligibility criteria (International Prospective Register of Systematic Reviews CRD42017080014). We classified evidence of cardiovascular toxicity as sufficient, probable, possible, or indeterminate for specific cardiovascular outcomes based on statistical significance, study quality, and size. Results From 113 systematic reviews, we found at least probable systematic review evidence of cardiovascular toxicity for 18 agents, including high- and all-grade hypertension for bevacizumab, ramucirumab, axitinib, cediranib, pazopanib, sorafenib, sunitinib, vandetanib, aflibercept, abiraterone, and enzalutamide, and all-grade hypertension for nintedanib; high- and all-grade arterial thromboembolism (includes cardiac and/or cerebral events) for bevacizumab and abiraterone, high-grade arterial thromboembolism for trastuzumab, and all-grade arterial thromboembolism for sorafenib and tamoxifen; high- and all-grade venous thromboembolism (VTE) for lenalidomide and thalidomide, high-grade VTE for cetuximab and panitumumab, and all-grade VTE for bevacizumab; high- and all-grade left ventricular ejection fraction decline or congestive heart failure for bevacizumab and trastuzumab, and all-grade left ventricular ejection fraction decline/congestive heart failure for pazopanib and sunitinib; and all-grade corrected QT interval prolongation for vandetanib. Conclusions Our review provides an accessible summary of the cardiovascular toxicity of targeted therapy to assist clinicians and patients when managing cardiovascular health.
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Affiliation(s)
- Marina T Van Leeuwen
- Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Steven Luu
- Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Howard Gurney
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Martin R Brown
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Sallie-Anne Pearson
- Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Kate Webber
- Department of Oncology, Monash Health, Clayton, Victoria, Australia.,School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
| | - Lee Hunt
- Cancer Voices NSW, Milsons Point, New South Wales, Australia
| | - Soojung Hong
- Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia.,Division of Oncology-Haematology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
| | - Geoffrey P Delaney
- Liverpool Cancer Therapy Centre, Liverpool, New South Wales, Australia.,Collaboration for Cancer Outcomes Research and Evaluation, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.,South Western Sydney Clinical School, University of New South Wales, Liverpool, New South Wales, Australia
| | - Claire M Vajdic
- Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia
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Choi SH, Kim KE, Park Y, Ju YW, Jung JG, Lee ES, Lee HB, Han W, Noh DY, Yoon HJ, Moon HG. Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data. Breast 2020; 54:25-30. [PMID: 32890789 PMCID: PMC7481564 DOI: 10.1016/j.breast.2020.08.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 08/07/2020] [Accepted: 08/10/2020] [Indexed: 12/15/2022] Open
Abstract
Background Aromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen. Methods We analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE. Results We included 47,569 women for the final analysis. Patients were classified into ‘No hormonal treatment (n = 18,807), ‘Switch (n = 2097)’, ‘Tamoxifen (n = 7081)’ and ‘AI (n = 19,584)’. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74–0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84–1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47–0.84). Conclusions Our results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.
Controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen. The protective effect of tamoxifen against cardiovascular events in elderly breast cancer patients that is not seen with AIs. Choice of hormonal therapy depends on patient’s cardiovascular or cerebrovascular risks.
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Affiliation(s)
- Sung Hyouk Choi
- Department of Biomedical Engineering, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Kyoung-Eun Kim
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Yujin Park
- Department of Biomedical Engineering, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Young Wook Ju
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Ji-Gwang Jung
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Eun Shin Lee
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Han-Byoel Lee
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Wonshik Han
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Dong-Young Noh
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Hyung-Jin Yoon
- Department of Biomedical Engineering, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
| | - Hyeong-Gon Moon
- Department of Surgery, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, 101 Daehakro, Jongno-gu, Seoul, Republic of Korea.
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Compensatory Estrogen Signal Is Capable of DNA Repair in Antiestrogen-Responsive Cancer Cells via Activating Mutations. JOURNAL OF ONCOLOGY 2020; 2020:5418365. [PMID: 32774370 PMCID: PMC7407016 DOI: 10.1155/2020/5418365] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 04/30/2020] [Accepted: 06/25/2020] [Indexed: 02/08/2023]
Abstract
Cancer cells are embarrassed human cells exhibiting the remnants of same mechanisms for DNA stabilization like patients have in their healthy cells. Antiestrogens target the liganded activation of ERs, which is the principal means of genomic regulation in both patients and their tumors. The artificial blockade of liganded ER activation is an emergency situation promoting strong compensatory actions even in cancer cells. When tumor cells are capable of an appropriate upregulation of ER signaling resulting in DNA repair, a tumor response may be detected. In contrast, when ER signaling is completely inhibited, tumor cells show unrestrained proliferation, and tumor growth may be observed. The laboratory investigations of genomic mechanisms in antiestrogen-responsive and antiestrogen-unresponsive tumor cells have considerably enhanced our knowledge regarding the principal regulatory capacity of estrogen signaling. In antiestrogen-responsive tumor cells, a compensatory increased expression and liganded activation of estrogen receptors (ERs) result in an apoptotic death. Conversely, in antiestrogen resistant tumors exhibiting a complete blockade of liganded ER activation, a compensatory effort for unliganded ER activation is characteristic, conferred by the increased expression and activity of growth factor receptors. However, even extreme unliganded ER activation is incapable of DNA restoration when the liganded ER activation is completely blocked. Researchers mistakenly suspect even today that in tumors growing under antiestrogen treatment, the increased unliganded activation of estrogen receptor via activating mutations is an aggressive survival technique, whilst it is a compensatory effort against the blockade of liganded ER activation. The capacity of liganded ERs for genome modification in emergency states provides possibilities for estrogen/ER use in medical practice including cancer cure.
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Moik F, Ay C, Pabinger I. Risk prediction for cancer-associated thrombosis in ambulatory patients with cancer: past, present and future. Thromb Res 2020; 191 Suppl 1:S3-S11. [DOI: 10.1016/s0049-3848(20)30389-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 12/14/2019] [Accepted: 12/23/2019] [Indexed: 01/29/2023]
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Lee M, Piao J, Jeon MJ. Risk Factors Associated with Endometrial Pathology in Premenopausal Breast Cancer Patients Treated with Tamoxifen. Yonsei Med J 2020; 61:317-322. [PMID: 32233174 PMCID: PMC7105402 DOI: 10.3349/ymj.2020.61.4.317] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 02/11/2020] [Accepted: 02/27/2020] [Indexed: 11/27/2022] Open
Abstract
PURPOSE To evaluate factors associated with endometrial pathology during tamoxifen use in premenopausal breast cancer (BC) patients. MATERIALS AND METHODS We reviewed the medical records of premenopausal BC patients treated with tamoxifen who underwent endometrial biopsy with or without hysteroscopy. Clinical characteristics were compared between women with endometrial pathology (endometrial hyperplasia or cancer) and those with normal histology or endometrial polyps. RESULTS Among 284 endometrial biopsies, endometrial hyperplasia was diagnosed in 7 patients (2.5%), endometrial cancer was diagnosed in 5 patients (1.8%), normal histology was noted in 146 patients (51.4%), and endometrial polyp was present in 114 patients (40.1%). When comparing women with endometrial cancer (n=5) to women with normal histology, abnormal uterine bleeding was more common (p=0.007), and endometrial thickness was greater (p=0.007) in women with endometrial cancer. Chemotherapy for BC was also more common in patients with endometrial cancer (p=0.037). When comparing women with endometrial polyps and those with endometrial hyperplasia or cancer, the presence of abnormal uterine bleeding was more common in patients with endometrial hyperplasia or cancer (p<0.001); however, tamoxifen duration and endometrial thickness did not differ significantly between the two groups. CONCLUSION In premenopausal BC patients treated with tamoxifen, abnormal uterine bleeding, increased endometrial thickness, and chemotherapy for BC were associated with the occurrence of endometrial cancer. These findings may provide useful information for gynecologic surveillance and counseling during tamoxifen treatment in premenopausal BC patients.
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Affiliation(s)
- Maria Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea
| | - Jinlan Piao
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Myung Jae Jeon
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea.
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Pineda-Moncusí M, Garcia-Giralt N, Diez-Perez A, Tusquets I, Servitja S, Albanell J, Prieto-Alhambra D, Nogués X. Thromboembolic, cardiovascular and overall mortality risks of aromatase inhibitors, compared with tamoxifen treatment: an outpatient-register-based retrospective cohort study. Ther Adv Med Oncol 2020; 12:1758835920909660. [PMID: 32231712 PMCID: PMC7097872 DOI: 10.1177/1758835920909660] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 01/20/2020] [Indexed: 01/12/2023] Open
Abstract
Background: Tamoxifen (TAM) and aromatase inhibitor (AI) therapies have been associated with increased risk of thromboembolic and cardiovascular events, respectively, in addition to other side effects. This study analysed the risk of these events and the overall survival (OS) benefit in breast cancer patients treated with AI, compared with TAM-treated patients, in a large population-based cohort. Methods: This observational cohort study included women diagnosed with breast cancer and treated with TAM or AI. Data were extracted from primary care records in a population database (SIDIAP, System for the Development of Research in Primary Care). Incidence rates of study outcomes are reported. Survival analyses included Kaplan–Meier estimation and Cox proportional hazards models. Sensitivity analysis was carried out, using Fine and Gray models to account for competing risk of death. Confounding was minimized using propensity score adjustment and inverse probability weighting (IPW) adjustment. Results: Data from 3082 postmenopausal women treated with TAM, and 18,455 treated with AI, were available. Adjusted hazard ratios (HRs) [95% confidence interval (CI)] for AI users, compared with TAM group, were 0.93 (95%CI 0.69–1.26) for thromboembolic events (TEEs); 1.13 (95%CI 0.79–1.63) for cardiovascular events, and 0.76 (95%CI 0.70–0.82) for mortality. Additional analyses using competing risk analysis had similar results, while IPW adjustment showed a potential risk of pulmonary embolism (PE) [2.26 (95%CI 1.02–4.97)] in AI-treated patients. Conclusions: AI users had >20% lower all-cause mortality compared with TAM users, without increasing risk to experience cardiovascular and TEEs. This would locate AI therapy on the first line in clinical practice. Thus, AI might be the most preferable option in adjuvant hormonal therapy choice.
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Affiliation(s)
- Marta Pineda-Moncusí
- IMIM (Hospital del Mar Research Institute), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Barcelona, Spain
| | - Natalia Garcia-Giralt
- IMIM (Hospital del Mar Research Institute), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Barcelona, Spain
| | - Adolfo Diez-Perez
- IMIM (Hospital del Mar Research Institute), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Barcelona, Spain
| | - Ignasi Tusquets
- Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona, Spain
| | - Sonia Servitja
- Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona, Spain
| | - Joan Albanell
- Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona, Spain Medical Oncology Department, Hospital del Mar-CIBERONC, Barcelona, Spain Universitat Pompeu Fabra, Barcelona, Spain
| | - Daniel Prieto-Alhambra
- Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, UK
| | - Xavier Nogués
- IMIM (Hospital del Mar Research Institute), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Barcelona, Spain
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Khosrow-Khavar F, Filion KB, Bouganim N, Suissa S, Azoulay L. Aromatase Inhibitors and the Risk of Cardiovascular Outcomes in Women With Breast Cancer: A Population-Based Cohort Study. Circulation 2020; 141:549-559. [PMID: 32065766 DOI: 10.1161/circulationaha.119.044750] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The association between aromatase inhibitors and cardiovascular outcomes among women with breast cancer is controversial. Given the discrepant findings from randomized controlled trials and observational studies, additional studies are needed to address this safety concern. METHODS We conducted a population-based cohort study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study population consisted of women newly diagnosed with breast cancer initiating hormonal therapy with aromatase inhibitors or tamoxifen between April 1, 1998, and February 29, 2016. We usedCox proportional hazards models with inverse probability of treatment and censoring weighting to estimate hazard ratios (HRs) with 95% CIs comparing new users of aromatase inhibitors with new users of tamoxifen for each of the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality). RESULTS The study population consisted of 23 525 patients newly diagnosed with breast cancer, of whom 17 922 initiated treatment with either an aromatase inhibitor or tamoxifen (8139 and 9783, respectively). The use of aromatase inhibitors was associated with a significantly increased risk of heart failure (incidence rate, 5.4 versus 1.8 per 1000 person-years; HR, 1.86 [95% CI, 1.14-3.03]) and cardiovascular mortality (incidence rate, 9.5 versus 4.7 per 1000 person-years; HR, 1.50 [95% CI, 1.11-2.04]) compared with the use of tamoxifen. Aromatase inhibitors were associated with elevated HRs, but with CIs including the null value, for myocardial infarction (incidence rate, 3.9 versus 1.8 per 1000 person-years; HR, 1.37 [95% CI, 0.88-2.13]) and ischemic stroke (incidence rate, 5.6 versus 3.2 per 1000 person-years; HR, 1.19 [95% CI, 0.82-1.72]). CONCLUSIONS In this population-based study, aromatase inhibitors were associated with increased risks of heart failure and cardiovascular mortality compared with tamoxifen. There were also trends toward increased risks, although nonsignificant, of myocardial infarction and ischemic stroke. The increased risk of cardiovascular events associated with aromatase inhibitors should be balanced with their favorable clinical benefits compared with tamoxifen.
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Affiliation(s)
- Farzin Khosrow-Khavar
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada (F.K.K., K.B.F., S.S., L.A.).,Department of Epidemiology, Biostatistics, and Occupational Health (F.K.K., K.B.F., S.S., L.A.), McGill University, Montreal, Quebec, Canada
| | - Kristian B Filion
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada (F.K.K., K.B.F., S.S., L.A.).,Department of Epidemiology, Biostatistics, and Occupational Health (F.K.K., K.B.F., S.S., L.A.), McGill University, Montreal, Quebec, Canada.,Division of Clinical Epidemiology, Department of Medicine (K.B.F.), McGill University, Montreal, Quebec, Canada
| | - Nathaniel Bouganim
- Gerald Bronfman Department of Oncology (N.B., L.A.), McGill University, Montreal, Quebec, Canada.,Department of Oncology, Cedar Cancer Center, McGill University Health Center, Montreal, Quebec, Canada (N.B.)
| | - Samy Suissa
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada (F.K.K., K.B.F., S.S., L.A.).,Department of Epidemiology, Biostatistics, and Occupational Health (F.K.K., K.B.F., S.S., L.A.), McGill University, Montreal, Quebec, Canada
| | - Laurent Azoulay
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada (F.K.K., K.B.F., S.S., L.A.).,Department of Epidemiology, Biostatistics, and Occupational Health (F.K.K., K.B.F., S.S., L.A.), McGill University, Montreal, Quebec, Canada.,Gerald Bronfman Department of Oncology (N.B., L.A.), McGill University, Montreal, Quebec, Canada
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Abstract
Patients with a current diagnosis of breast cancer are enjoying dramatic cure rates and survivorship secondary to an increase in awareness, earlier detection, and more effective therapies. Although strategies such as Breast Cancer Awareness Month in October focus on early detection, lifestyle changes are seldom discussed other than dietary concerns and physical activity. Lifestyle modifications centered on diet and exercise have been demonstrated to affect overall disease-free survival in breast cancer. Since the early 2000s, the role of the human gut microbiota and its relation to breast cancer has become a major area of interest in the scientific and medical community. We live and survive owing to the symbiotic relationship with the microorganisms within us: the human microbiota. Scientific advances have identified a subset of the gut microbiota: the estrobolome, those bacteria that have the genetic capability to metabolize estrogen, which plays a key role in most breast cancers. Recent research provides evidence that the gut microbiome plays a substantial role in estrogen regulation. Gut microbiota diversity appears to be an essential component of overall health, including breast health. Future research attention should include a more extensive focus on the role of the human gut microbiota in breast cancer.
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Affiliation(s)
- Balazs I Bodai
- The Breast Cancer Survivorship Institute, Kaiser Permanente, Sacramento, CA
| | - Therese E Nakata
- The Breast Cancer Survivorship Institute, Kaiser Permanente, Sacramento, CA
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He Y, Zhang J, Shen G, Liu L, Zhao Q, Lu X, Yang H, Hong D. Aromatase inhibitors and risk of cardiovascular events in breast cancer patients: a systematic review and meta-analysis. BMC Pharmacol Toxicol 2019; 20:62. [PMID: 31665091 PMCID: PMC6820915 DOI: 10.1186/s40360-019-0339-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 09/20/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Cardiovascular events (CVEs) was considered as one of the primary cause to reduce the quality of life in breast cancer patients with aromatase inhibitors (AIs) treatment, which has not been sufficiently addressed. The aim of this study was to assess the correlation between risk of CVEs and AIs in patients with breast cancer. METHODS Included studies were obtained from the databases of Embase, Pubmed, Cochrane Library, Clinical Trials.gov, and reference lists. The main outcome measures were overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Furthermore, the association and the risk differences among different tumor types, AIs,ages,or treatment regimens were conducted. Fixed-effect or random-effect models were applied in the statistical analyses according to the heterogeneity. Our analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS Seventeen studies, which included 44,411 subjects, were included in our analyses. The overall incidence of CVEs in AIs group was 13.02% (95% CI: 8.15-20.17%) and almost all of the high-grade CVEs occurred in patients treated with AIs. The pooled ORs of CVEs was 0.9940 (95% CI: 0.8545-1.1562). Under sub-group analysis, the incidence of CVEs related to exemestane was higher than that of controls (OR = 1.1564, 95% CI: 1.0656-1.2549), but no statistical differences in risk of CVEs were found in other sub-group analysis. No evidence of publication bias was found for incidence of CVEs in our meta-analysis by a funnel plot. CONCLUSIONS These results suggest that patients with breast cancer treated with AIs do not have a significant risk of developing CVEs in comparison with the controls, and exemestane might not be considered as the alternative AI to the breast cancer patients from the perspective of CVEs. Further studies are recommended to investigate this association and the risk differences among different tumor types, AIs or treatment regimens.
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Affiliation(s)
- Yang He
- Department of Pharmacy, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.,College of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310003, People's Republic of China
| | - Jianhua Zhang
- Department of Management, the Logistics Service Center of Municipal Government, Hangzhou, 310019, People's Republic of China
| | - Guofang Shen
- Loma Linda University School of Pharmacy, Loma Linda, CA, 92354, USA
| | - Lin Liu
- Department of Pharmacy, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Qingwei Zhao
- Department of Pharmacy, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Xiaoyang Lu
- Department of Pharmacy, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China
| | - Hongyu Yang
- Department of Pharmacy, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.
| | - Dongsheng Hong
- Department of Pharmacy, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.
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Raglan O, Kalliala I, Markozannes G, Cividini S, Gunter MJ, Nautiyal J, Gabra H, Paraskevaidis E, Martin-Hirsch P, Tsilidis KK, Kyrgiou M. Risk factors for endometrial cancer: An umbrella review of the literature. Int J Cancer 2019; 145:1719-1730. [PMID: 30387875 DOI: 10.1002/ijc.31961] [Citation(s) in RCA: 332] [Impact Index Per Article: 55.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 10/19/2018] [Indexed: 03/25/2024]
Abstract
Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over- or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer. Systematic reviews or meta-analyses of observational studies evaluating the association between non-genetic risk factors and risk of developing or dying from endometrial cancer were identified from inception to April 2018 using PubMed, the Cochrane database and manual reference screening. Evidence was graded strong, highly suggestive, suggestive or weak based on statistical significance of random-effects summary estimate, largest study included, number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings. We identified 171 meta-analyses investigating associations between 53 risk factors and endometrial cancer incidence and mortality. Risk factors were categorised: anthropometric indices, dietary intake, physical activity, medical conditions, hormonal therapy use, biochemical markers, gynaecological history and smoking. Of 127 meta-analyses including cohort studies, three associations were graded with strong evidence. Body mass index and waist-to-hip ratio were associated with increased cancer risk in premenopausal women (RR per 5 kg/m2 1.49; CI 1.39-1.61) and for total endometrial cancer (RR per 0.1unit 1.21; CI 1.13-1.29), respectively. Parity reduced risk of disease (RR 0.66, CI 0.60-0.74). Of many proposed risk factors, only three had strong association without hints of bias. Identification of genuine risk factors associated with endometrial cancer may assist in developing targeted prevention strategies for women at high risk.
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Affiliation(s)
- Olivia Raglan
- Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, United Kingdom
- Queen Charlotte's and Chelsea - Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Ilkka Kalliala
- Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, United Kingdom
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Georgios Markozannes
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | | | - Marc J Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France
| | - Jaya Nautiyal
- Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Hani Gabra
- Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, United Kingdom
- Early Clinical Development, IMED Biotech Unit, Cambridge, United Kingdom
| | | | - Pierre Martin-Hirsch
- Department of Gynaecologic Oncology, Lancashire Teaching Hospitals, Preston, United Kingdom
- Department of Biophysics, University of Lancaster, Lancaster, United Kingdom
| | - Kostas K Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Maria Kyrgiou
- Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, United Kingdom
- Queen Charlotte's and Chelsea - Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
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Jeon J, Kim SE, Lee DY, Choi D. Factors associated with endometrial pathology during tamoxifen therapy in women with breast cancer: a retrospective analysis of 821 biopsies. Breast Cancer Res Treat 2019; 179:125-130. [DOI: 10.1007/s10549-019-05448-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 09/13/2019] [Indexed: 10/26/2022]
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Chiofalo B, Mazzon I, Di Angelo Antonio S, Amadore D, Vizza E, Laganà AS, Vocaturo G, Calagna G, Favilli A, Palmara V, Maranto M, Vitale SG, Cucinella G, Granese R, Ghezzi F, Sperduti I, Triolo O. Hysteroscopic Evaluation of Endometrial Changes in Breast Cancer Women with or without Hormone Therapies: Results from a Large Multicenter Cohort Study. J Minim Invasive Gynecol 2019; 27:832-839. [PMID: 31425735 DOI: 10.1016/j.jmig.2019.08.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 07/30/2019] [Accepted: 08/04/2019] [Indexed: 10/26/2022]
Abstract
STUDY OBJECTIVE The primary aim of our study was to investigate the incidence of endometrial pathologies, especially endometrial cancer, in women with breast cancer treated with tamoxifen (TAM), aromatase inhibitors (AIs), or receiving no treatment (NT). The secondary aim was to identify, in this cohort, ultrasonographic findings that represent robust indications for hysteroscopy and endometrial biopsy, to avoid unnecessary second-level diagnostic procedures. DESIGN Multicenter retrospective cohort study (Clinical Trial ID: NCT03898947). SETTING Data were collected from different Italian centers: Regina Elena National Cancer Institute of Rome, Arbor Vitae Centre of Rome, Gaetano Martino University Hospital of Messina, and Villa Sofia-Cervello Hospital of Palermo. PATIENTS We selected and consecutively included patients with a history of breast cancer who had undergone hysteroscopy for ultrasonographic or clinical indications between January 2007 and December 2016. INTERVENTIONS Diagnostic hysteroscopy with endometrial biopsy or operative hysteroscopy, when clinically indicated. MEASUREMENTS AND MAIN RESULTS A higher percentage of patients in the TAM and AI groups had a normal endometrium compared with those in the NT group, whereas the incidence of endometrial polyps was higher in the NT group than in the others; no significant differences were observed among the 3 groups for other benign conditions or for premalignant and malignant uterine diseases, such as endometrial atypical hyperplasia and adenocarcinoma. CONCLUSION TAM treatment does not seem to be associated with a higher rate of endometrial cancer in women with breast cancer compared with women treated with AIs or NT.
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Affiliation(s)
- Benito Chiofalo
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Ivano Mazzon
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Silvia Di Angelo Antonio
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Donatella Amadore
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Enrico Vizza
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Antonio Simone Laganà
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti).
| | - Giuseppe Vocaturo
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Gloria Calagna
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Alessandro Favilli
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Vittorio Palmara
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Marianna Maranto
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Salvatore Giovanni Vitale
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Gaspare Cucinella
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Roberta Granese
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Fabio Ghezzi
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Isabella Sperduti
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
| | - Onofrio Triolo
- Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Drs. Chiofalo, Vizza, and Vocaturo); Arbor Vitae Centre, Nuova Villa Claudia Clinic, Rome, Italy (Drs. Mazzon and Di Angelo Antonio); Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy (Drs. Amadore, Palmara, Granese, and Triolo); Department of Obstetrics and Gynecology, Filippo Del Ponte Hospital, University of Insubria, Varese, Italy (Drs. Laganà and Ghezzi); Gynecology and Obstetrics Unit, Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy (Drs. Calagna, Maranto, and Cucinella); Department of Surgical and Biomedical Sciences, Section of Obstetrics and Gynecology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy (Dr. Favilli); Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy (Dr.Vitale); Biostatistical Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy (Dr. Sperduti)
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Cheung YM, Ramchand SK, Yeo B, Grossmann M. Cardiometabolic Effects of Endocrine Treatment of Estrogen Receptor-Positive Early Breast Cancer. J Endocr Soc 2019; 3:1283-1301. [PMID: 31259291 PMCID: PMC6595530 DOI: 10.1210/js.2019-00096] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 05/01/2019] [Indexed: 12/15/2022] Open
Abstract
Estrogen receptor-positive early breast cancer is common and has a relatively good prognosis. It shares risk factors with cardiovascular disease, and cardiovascular disease is an important competing cause of mortality. Adjuvant endocrine therapy with aromatase inhibitors (requiring concomitant ovarian suppression in premenopausal women) or selective estrogen receptor modulators (usually tamoxifen) exert oncologic benefits by respectively inhibiting estradiol synthesis or breast estrogen receptor signaling. Aromatase inhibitors cause systemic estradiol depletion. Tamoxifen has mixed agonistic/antagonistic effects in a tissue-dependent fashion. Given that estrogens modulate cardiometabolic risk, a review of the effects of endocrine therapy on cardiometabolic outcomes is pertinent. The current, but limited, evidence suggests that tamoxifen treatment, although associated with increases in body fat, hepatic steatosis, serum triglycerides, and diabetes risk, modestly reduces low-density lipoprotein cholesterol and lipoprotein(a) and may have favorable effects on markers of subclinical atherosclerosis. Tamoxifen is associated with either no effect on, or a reduction in, cardiovascular events, and it is associated with an increase in venous thromboembolic events. Aromatase inhibitors, although fewer studies are available and often confounded by comparison with tamoxifen, have not been consistently associated with adverse changes in cardiometabolic risk factors or increases in cardiovascular events. Further clinical trials designed to evaluate cardiometabolic outcomes are needed to more accurately determine the effects of endocrine therapy on cardiovascular risks, to inform individualized decisions regarding choice and duration of endocrine therapy, and to implement evidence-based strategies to mitigate cardiometabolic risks. In the meantime, although breast cancer-specific evidence for benefit of lifestyle measures is available and recommended routinely, proactive monitoring and treatment of cardiovascular risk factors should follow general population recommendations.
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Affiliation(s)
- Yee-Ming Cheung
- Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
- Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria Australia
| | - Sabashini K Ramchand
- Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
- Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria Australia
| | - Belinda Yeo
- Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
- Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
| | - Mathis Grossmann
- Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
- Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria Australia
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Sohrabji F, Okoreeh A, Panta A. Sex hormones and stroke: Beyond estrogens. Horm Behav 2019; 111:87-95. [PMID: 30713101 PMCID: PMC6527470 DOI: 10.1016/j.yhbeh.2018.10.010] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 10/22/2018] [Accepted: 10/22/2018] [Indexed: 12/11/2022]
Abstract
Stroke risk and poor stroke outcomes in postmenopausal women have usually beeen attributed to decreased levels of estrogen. However, two lines of evidence suggest that this hormone may not be solely responsible for elevated stroke risk in this population. First, the increased risk for CVD and stroke occurs much earlier than menopause at a time when estrogen levels are not yet reduced. Second, estrogen therapy has not successfully reduced stroke risk in all studies. Other sex hormones may therefore also contribute to stroke risk. Prior to menopause, levels of the gonadotrophin Follicle Stimulating Hormone (FSH) are elevated while levels of the gonadal peptide inhibin are lowered, indicating an overall decrease in ovarian reserve. Similarly, reduced estrogen levels at menopause significantly increase the ratio of androgens to estrogens. In view of the evidence that androgens may be unfavorable for CVD and stroke, this elevated ratio of testosterone to estrogen may also contribute to the postmenopause-associated stroke risk. This review synthesizes evidence from different clinical populations including natural menopause, surgical menopause, women on chemotherapy, and preclinical stroke models to dissect the role of ovarian hormones and stroke risk and outcomes.
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Affiliation(s)
- Farida Sohrabji
- Women's Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, Bryan, TX 77807, United States of America.
| | - Andre Okoreeh
- Women's Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, Bryan, TX 77807, United States of America
| | - Aditya Panta
- Women's Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M College of Medicine, Bryan, TX 77807, United States of America
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Attenuated peripheral endothelial function among women treated with aromatase inhibitors for breast cancer. Coron Artery Dis 2018; 29:687-693. [DOI: 10.1097/mca.0000000000000666] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Emons G, Steiner E, Vordermark D, Uleer C, Bock N, Paradies K, Ortmann O, Aretz S, Mallmann P, Kurzeder C, Hagen V, van Oorschot B, Höcht S, Feyer P, Egerer G, Friedrich M, Cremer W, Prott FJ, Horn LC, Prömpeler H, Langrehr J, Leinung S, Beckmann MW, Kimmig R, Letsch A, Reinhardt M, Alt-Epping B, Kiesel L, Menke J, Gebhardt M, Steinke-Lange V, Rahner N, Lichtenegger W, Zeimet A, Hanf V, Weis J, Mueller M, Henscher U, Schmutzler RK, Meindl A, Hilpert F, Panke JE, Strnad V, Niehues C, Dauelsberg T, Niehoff P, Mayr D, Grab D, Kreißl M, Witteler R, Schorsch A, Mustea A, Petru E, Hübner J, Rose AD, Wight E, Tholen R, Bauerschmitz GJ, Fleisch M, Juhasz-Boess I, Sigurd L, Runnebaum I, Tempfer C, Nothacker MJ, Blödt S, Follmann M, Langer T, Raatz H, Wesselmann S, Erdogan S. Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Nummer 032/034-OL, April 2018) - Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer. Geburtshilfe Frauenheilkd 2018; 78:949-971. [PMID: 30364388 PMCID: PMC6195426 DOI: 10.1055/a-0713-1218] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 08/22/2018] [Indexed: 12/30/2022] Open
Abstract
Summary
The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG).
Purpose
The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers.
Methods
The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online.
Recommendations
Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.
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Affiliation(s)
- Günter Emons
- Klinik für Gynäkologie und Geburtshilfe, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Eric Steiner
- Frauenklinik, GPR Klinikum Rüsselsheim am Main, Rüsselsheim, Germany
| | | | - Christoph Uleer
- Facharzt für Frauenheilkunde und Geburtshilfe, Hildesheim, Hildesheim, Germany
| | - Nina Bock
- Klinik für Gynäkologie und Geburtshilfe, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Kerstin Paradies
- Konferenz Onkologischer Kranken- und Kinderkrankenpflege, Hamburg, Germany
| | - Olaf Ortmann
- Frauenheilkunde und Geburtshilfe, Universität Regensburg, Regensburg, Germany
| | - Stefan Aretz
- Institut für Humangenetik, Universität Bonn, Zentrum für erbliche Tumorerkrankungen, Universitätsklinikum Bonn, Bonn, Germany
| | | | | | - Volker Hagen
- Klinik für Innere Medizin II, St.-Johannes-Hospital Dortmund, Dortmund, Germany
| | - Birgitt van Oorschot
- Interdisziplinäres Zentrum Palliativmedizin, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Stefan Höcht
- Xcare, Praxis für Strahlentherapie, Saarlouis, Saarlouis, Germany
| | - Petra Feyer
- Klinik für Strahlentherapie und Radioonkologie, Vivantes Klinikum Neukölln, Berlin, Germany
| | - Gerlinde Egerer
- Zentrum für Innere Medizin, Universitätsklinikum Heidelberg, Heidelberg, Germany
| | | | | | | | | | - Heinrich Prömpeler
- Klinik für Frauenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany
| | - Jan Langrehr
- Klinik für Allgemein-, Gefäß- und Viszeralchirurgie, Martin-Luther-Krankenhaus, Berlin, Germany
| | | | | | - Rainer Kimmig
- Women's Department, University Hospital of Essen, Essen, Germany
| | - Anne Letsch
- Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité, Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
| | - Michael Reinhardt
- Klinik für Nuklearmedizin, Pius Hospital Oldenburg, Oldenburg, Germany
| | - Bernd Alt-Epping
- Klinik für Palliativmedizin, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Ludwig Kiesel
- Obstetrics and Gynecology, Reproductive Medicine, University of Muenster, Germany, Münster, Germany
| | - Jan Menke
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Marion Gebhardt
- Frauenselbsthilfe nach Krebs e. V., Erlangen, Erlangen/Forchheim, Germany
| | - Verena Steinke-Lange
- MGZ - Medizinisch Genetisches Zentrum, München und Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, München, Germany
| | - Nils Rahner
- Institut für Humangenetik, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | - Werner Lichtenegger
- Frauenklinik Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany
| | - Alain Zeimet
- Frauenheilkunde, Medizinische Universität Innsbruck, Innsbruck, Austria
| | - Volker Hanf
- Frauenklinik Nathanstift - Klinikum Fürth, Fürth, Germany
| | - Joachim Weis
- Stiftungsprofessur Selbsthilfeforschung, Tumorzentrum/CCC Freiburg, Universitätsklinikum Freiburg, Freiburg, Germany
| | - Michael Mueller
- Universitätsklinik für Frauenheilkunde, Inselspital Bern, Bern, Switzerland
| | | | - Rita K Schmutzler
- Center for Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany
| | - Alfons Meindl
- Frauenklinik am Klinikum rechts der Isar, München, Germany
| | - Felix Hilpert
- Mammazentrum, Krankenhaus Jerusalem, Hamburg, Germany
| | - Joan Elisabeth Panke
- Medizinischer Dienst des Spitzenverbandes Bund der Krankenkassen e. V., Essen, Germany
| | - Vratislav Strnad
- Strahlenklinik, Universitätsklinikum Erlangen, CCC ER-EMN, Universitäts-Brustzentrum Franken, Erlangen, Germany
| | | | - Timm Dauelsberg
- Winkelwaldklinik Nordrach, Fachklinik für onkologische Rehabilitation, Nordrach, Germany
| | - Peter Niehoff
- Strahlenklinik, Sana Klinikum Offenbach, Offenbach, Germany
| | - Doris Mayr
- Pathologisches Institut, LMU München, München, Germany
| | - Dieter Grab
- Frauenklinik Klinikum Harlaching, München, Germany
| | - Michael Kreißl
- Universitätsklinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg, Magdeburg, Germany
| | - Ralf Witteler
- Obstetrics and Gynecology, Reproductive Medicine, University of Muenster, Germany, Münster, Germany
| | | | | | - Edgar Petru
- Frauenheilkunde, Medizinische Universität Graz, Graz, Austria
| | - Jutta Hübner
- Klinikum für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
| | | | - Edward Wight
- Frauenklinik des Universitätsspitals Basel, Basel, Switzerland
| | - Reina Tholen
- Deutscher Verband für Physiotherapie, Referat Bildung und Wissenschaft, Köln, Germany
| | - Gerd J Bauerschmitz
- Klinik für Gynäkologie und Geburtshilfe, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Markus Fleisch
- Landesfrauenklinik, HELIOS Universitätsklinikum Wuppertal, Wuppertal, Germany
| | - Ingolf Juhasz-Boess
- Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Saar, Germany
| | - Lax Sigurd
- Institut für Pathologie, Landeskrankenhaus Graz West, Graz, Austria
| | | | - Clemens Tempfer
- Marien Hospital Herne - Universitätsklinikum der Ruhr-Universität Bochum, Herne, Germany
| | | | | | - Markus Follmann
- Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
| | - Thomas Langer
- Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
| | - Heike Raatz
- Institut für Klinische Epidemiologie & Biostatistik (CEB), Basel, Switzerland
| | | | - Saskia Erdogan
- Klinik für Gynäkologie und Geburtshilfe, Universitätsmedizin Göttingen, Göttingen, Germany
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Matthews A, Stanway S, Farmer RE, Strongman H, Thomas S, Lyon AR, Smeeth L, Bhaskaran K. Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review. BMJ 2018; 363:k3845. [PMID: 30297439 PMCID: PMC6174332 DOI: 10.1136/bmj.k3845] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVE To investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer. DESIGN Systematic review and meta-analysis of randomised controlled trials and observational studies. DATA SOURCES Medline and Embase up until June 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Studies were included if they investigated the risk of a specific cardiovascular disease outcome associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of non-metastatic breast cancer. APPRAISAL AND DATA EXTRACTION Relevant studies were originally identified and results extracted by one researcher, with a full replication of the study identification process by a combination of two other researchers. The Cochrane Collaboration's tool for assessing risk of bias was used to assess risk of bias in randomised controlled trials, and this tool was adapted to assess risk of bias in observational studies. RESULTS 26 studies were identified, with results for seven specific cardiovascular disease outcomes (venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease). Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non-users and aromatase inhibitor users. Results were also consistent with a higher risk of the vascular diseases myocardial infarction and angina in aromatase inhibitor users compared with tamoxifen users, but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes. Data were limited, and evidence was generally inconsistent for all other cardiovascular disease outcomes. CONCLUSION This review has collated substantial randomised controlled trial and observational evidence on the effect of endocrine therapies on several specific cardiovascular disease outcomes including venous thromboembolism and myocardial infarction, progressing knowledge. Although the choice of aromatase inhibitor or tamoxifen will primarily be based on the effectiveness against the recurrence of breast cancer, this review shows that the individual patient's risk of venous or arterial vascular disease should be an important secondary consideration. SYSTEMATIC REVIEW REGISTRATION Prospero CRD42017065944.
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Affiliation(s)
- Anthony Matthews
- Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | | | - Ruth E Farmer
- Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Helen Strongman
- Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Sara Thomas
- Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Alexander R Lyon
- Faculty of Medicine, Imperial College London, London, UK
- Royal Brompton Hospital, London, UK
| | - Liam Smeeth
- Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Krishnan Bhaskaran
- Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
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