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Kumar N, Gera K, Patel P, Lakhera KK, Singh S, Gurjar B, Kumar A, Singhal P, Gora B, Sharma RG. From Statistics to Stories: Unveiling the Epidemiology of Breast Carcinoma in Northwestern India. Indian J Surg Oncol 2025; 16:543-549. [PMID: 40337059 PMCID: PMC12052726 DOI: 10.1007/s13193-024-02104-8] [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: 08/25/2023] [Accepted: 09/21/2024] [Indexed: 05/09/2025] Open
Abstract
After receiving the pathology report for breast cancer, the first question most patients ask their doctor is about their journey ahead. The type of cancer and how it spreads can give us an idea of what to expect during follow-up. Unfortunately, there is a lack of reporting, management, and documentation of breast cancer cases in India, resulting in a shortage of information on the different types of breast cancer. To address this issue, a study was conducted to gain a better understanding of the pattern of breast carcinoma in Northwestern India. A total of 2619 breast cancer pathology reports were gathered from four major diagnostic centres in Northwest India. Out of all breast cancer patients, 97.74% (2560) were women, while men accounted for only 2.25% (59) of the sample. At the time of diagnosis, 72% of patients were in stages III and IV, while only 28% of patients were in the early stages of cancer (stages I and II). The most common type of breast cancer was infiltrating duct carcinoma (IDC), which constituted 80.71% (2114/2619) of all malignant lesions. infiltrating lobular carcinoma was the second most common pathology, accounting for 5.38% (141/2619) of all cases. The rarer pathologies had a presentation rate below 10%. Our study revealed the most common symptom as a painless lump. Significant majority presented in advanced stages. An alarming 20% presented with foul-smelling ulceration or fungation of the skin. Varied presentations of breast cancer subtypes were evident. As the age-old saying goes-the 'most common' is often ignored as a large portion of the researcher's attention is focused on 'rarer stuff'. Similarly, IDC being the commonest deserves most of our attention. Not just the histology but its grades too. The lack of awareness regarding the risk factors and early detection methods of breast cancer is unfortunately even prevalent in 49% of healthcare workers. What India needs are more data reporting, timely diagnostic strategies, standardized reporting for pathology, and guideline-based management strategies. Increasing data collection electronically in the coming years will help India in displaying more data.
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Affiliation(s)
- Naina Kumar
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, Jaipur, Rajasthan 302004 India
| | - Kriti Gera
- Department of Internal Medicine, University of Florida College of Medicine, Gainesville, USA
| | - Pinakin Patel
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, Jaipur, Rajasthan 302004 India
| | - Kamal Kishore Lakhera
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, Jaipur, Rajasthan 302004 India
| | - Suresh Singh
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, Jaipur, Rajasthan 302004 India
| | - Bhairulal Gurjar
- Department of Pediatric Surgery, SMS Medical College and Attached Group of Hospitals, Jaipur, Rajasthan India
| | - Arjun Kumar
- Department of Internal Medicine, All India Institute of Medical Sciences, Delhi, India
| | - Pranav Singhal
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, Jaipur, Rajasthan 302004 India
| | - Bhoopendra Gora
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, Jaipur, Rajasthan 302004 India
| | - Raj Govind Sharma
- Department of Surgical Oncology, Mahatma Gandhi Medical College and Attached Hospital, Jaipur, Rajasthan India
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Singh A, Singh K, Sharma A, Sharma S, Batra K, Joshi K, Singh B, Kaur K, Chadha R, Bedi PMS. Mechanistic insight and structure activity relationship of isatin-based derivatives in development of anti-breast cancer agents. Mol Cell Biochem 2024; 479:1165-1198. [PMID: 37329491 DOI: 10.1007/s11010-023-04786-0] [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: 03/01/2023] [Accepted: 06/07/2023] [Indexed: 06/19/2023]
Abstract
Breast cancer is most common in women and most difficult to manage that causes highest mortality and morbidity among all diseases and posing significant threat to mankind as well as burden on healthcare system. In 2020, 2.3 million women were diagnosed with breast cancer and it was responsible for 685,000 deaths globally, suggesting the severity of this disease. Apart from that, relapsing of cases and resistance among available anticancer drugs along with associated side effects making the situation even worse. Therefore, it is a global emergency to develop potent and safer antibreast cancer agents. Isatin is most versatile and flying one nucleus which is an integral competent and various anticancer agent in clinical practice and widely used by various research groups around the globe for development of novel, potent, and safer antibreast cancer agents. This review will shed light on the structural insights and antiproliferative potential of various isatin-based derivatives developed for targeting breast cancer in last three decades that will help researchers in design and development of novel, potent, and safer isatin-based antibreast cancer agents.
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Affiliation(s)
- Atamjit Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
| | - Karanvir Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Aman Sharma
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Sambhav Sharma
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Kevin Batra
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Kaustubh Joshi
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Brahmjeet Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Kirandeep Kaur
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Renu Chadha
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India
| | - Preet Mohinder Singh Bedi
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
- Drug and Pollution Testing Laboratory, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
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3
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Flaherty RL, Sflomos G, Brisken C. Is There a Special Role for Ovarian Hormones in the Pathogenesis of Lobular Carcinoma? Endocrinology 2024; 165:bqae031. [PMID: 38551031 PMCID: PMC10988861 DOI: 10.1210/endocr/bqae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Indexed: 04/04/2024]
Abstract
Lobular carcinoma represent the most common special histological subtype of breast cancer, with the majority classed as hormone receptor positive. Rates of invasive lobular carcinoma in postmenopausal women have been seen to increase globally, while other hormone receptor-positive breast cancers proportionally have not followed the same trend. This has been linked to exposure to exogenous ovarian hormones such as hormone replacement therapy. Reproductive factors resulting in increased lifetime exposure to endogenous ovarian hormones have also been linked to an increased risk of lobular breast cancer, and taken together, these data make a case for the role of ovarian hormones in the genesis and progression of the disease. In this review, we summarize current understanding of the epidemiological associations between ovarian hormones and lobular breast cancer and highlight mechanistic links that may underpin the etiology and biology.
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Affiliation(s)
- Renée L Flaherty
- Division of Breast Cancer Research, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, UK
| | - George Sflomos
- Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
| | - Cathrin Brisken
- Division of Breast Cancer Research, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, UK
- Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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Gasparini A, Humphreys K. A natural history and copula-based joint model for regional and distant breast cancer metastasis. Stat Methods Med Res 2022; 31:2415-2430. [PMID: 36120891 PMCID: PMC9703386 DOI: 10.1177/09622802221122410] [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] [Indexed: 12/15/2022]
Abstract
The few existing statistical models of breast cancer recurrence and progression to distant metastasis are predominantly based on multi-state modelling. While useful for summarising the risk of recurrence, these provide limited insight into the underlying biological mechanisms and have limited use for understanding the implications of population-level interventions. We develop an alternative, novel, and parsimonious approach for modelling latent tumour growth and spread to local and distant metastasis, based on a natural history model with biologically inspired components. We include marginal sub-models for local and distant breast cancer metastasis, jointly modelled using a copula function. Different formulations (and correlation shapes) are allowed, thus we can incorporate and directly model the correlation between local and distant metastasis flexibly and efficiently. Submodels for the latent cancer growth, the detection process, and screening sensitivity, together with random effects to account for between-patients heterogeneity, are included. Although relying on several parametric assumptions, the joint copula model can be useful for understanding - potentially latent - disease dynamics, obtaining patient-specific, model-based predictions, and studying interventions at a population level, for example, using microsimulation. We illustrate this approach using data from a Swedish population-based case-control study of postmenopausal breast cancer, including examples of useful model-based predictions.
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Affiliation(s)
- Alessandro Gasparini
- Alessandro Gasparini, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, SE-171 77 Stockholm, Sweden.
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Isheden G, Humphreys K. A unifying framework for continuous tumour growth modelling of breast cancer screening data. Math Biosci 2022; 353:108897. [PMID: 36037859 DOI: 10.1016/j.mbs.2022.108897] [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: 01/18/2022] [Revised: 08/22/2022] [Accepted: 08/22/2022] [Indexed: 11/19/2022]
Abstract
The aim of the current article is to present theory that can help unify continuous growth approaches for modelling breast cancer tumour growth based on human data. We present a framework that has three main features: a general likelihood function to account for patient specific screening regiments; stable disease assumptions describing tumour population dynamics; and mathematical models describing tumour growth, individual variation in tumour growth, a hazard for symptomatic detection, and screening test sensitivity. The framework is able to incorporate any random effects distributions for the tumour growth rate parameter, any hazard functions for symptomatic tumour detection, as well as any monotonously increasing function for the tumour growth model. Based on a sample of 1902 incident breast cancer cases with data on mammography screening, we show how the framework can be used to estimate tumour growth based on different growth functions.
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Lubián López DM. Management of genitourinary syndrome of menopause in breast cancer survivors: An update. World J Clin Oncol 2022; 13:71-100. [PMID: 35316932 PMCID: PMC8894268 DOI: 10.5306/wjco.v13.i2.71] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 09/19/2021] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
There is increasing attention about managing the adverse effects of adjuvant therapy (Chemotherapy and anti-estrogen treatment) for breast cancer survivors (BCSs). Vulvovaginal atrophy (VVA), caused by decreased levels of circulating estrogen to urogenital receptors, is commonly experienced by this patients. Women receiving antiestrogen therapy, specifically aromatase inhibitors, often suffer from vaginal dryness, itching, irritation, dyspareunia, and dysuria, collectively known as genitourinary syndrome of menopause (GSM), that it can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of quality of life (QoL). The worsening of QoL in these patients due to GSM symptoms can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly. The diagnosis of VVA is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Systemic estrogen treatment is contraindicated in BCSs. In these patients, GSM may be prevented, reduced and managed in most cases but this requires early recognition and appropriate treatment, but it is normally undertreated by oncologists because of fear of cancer recurrence, specifically when considering treatment with vaginal estrogen therapy (VET) because of unknown levels of systemic absorption of estradiol. Lifestyle modifications and nonhormonal treatments (vaginal moisturizers, lubricants, and gels) are the first-line treatment for GSM both in healthy women as BCSs, but when these are not effective for symptom relief, other options can be considered, such as VET, ospemifene, local androgens, intravaginal dehydroepiandrosterone (prasterone), or laser therapy (erbium or CO2 Laser). The present data suggest that these therapies are effective for VVA in BCSs; however, safety remains controversial and a there is a major concern with all of these treatments. We review current evidence for various nonpharmacologic and pharmacologic therapeutic modalities for GSM in BCSs and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research. We include recommendations for an approach to the management of GSM in women at high risk for breast cancer, women with estrogen-receptor positive breast cancers, women with triple-negative breast cancers, and women with metastatic disease.
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Affiliation(s)
- Daniel María Lubián López
- Department of Mother and Child Health and Radiology, Faculty of Medicine, University of Cadiz, Cádiz 11100, Spain
- Department of Obstetrics and Gynecology Service, University Hospital of Jerez de la Frontera, Jerez de la Frontera 11407, Spain
- Department of Obstetrics and Gynecology, Hospital Viamed Bahía de Cádiz, Chiclana de la Frontera 11130, Cádiz, a Spain
- Department of Obstetrics and Gynecology, Hospital Quirónsalud Campo de Gibraltar, Los Barrios 11379, Cádiz, Spain
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Gasparini A, Humphreys K. Estimating latent, dynamic processes of breast cancer tumour growth and distant metastatic spread from mammography screening data. Stat Methods Med Res 2022; 31:862-881. [PMID: 35103530 PMCID: PMC9099158 DOI: 10.1177/09622802211072496] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We propose a framework for jointly modelling tumour size at diagnosis and time to
distant metastatic spread, from diagnosis, based on latent dynamic sub-models of
growth of the primary tumour and of distant metastatic detection. The framework
also includes a sub-model for screening sensitivity as a function of latent
tumour size. Our approach connects post-diagnosis events to the natural history
of cancer and, once refined, may prove useful for evaluating new interventions,
such as personalised screening regimes. We evaluate our model-fitting procedure
using Monte Carlo simulation, showing that the estimation algorithm can retrieve
the correct model parameters, that key patterns in the data can be captured by
the model even with misspecification of some structural assumptions, and that,
still, with enough data it should be possible to detect strong
misspecifications. Furthermore, we fit our model to observational data from an
extension of a case-control study of post-menopausal breast cancer in Sweden,
providing model-based estimates of the probability of being free from detected
distant metastasis as a function of tumour size, mode of detection (of the
primary tumour), and screening history. For women with screen-detected cancer
and two previous negative screens, the probabilities of being free from detected
distant metastases 5 years after detection and removal of the primary tumour are
0.97, 0.89 and 0.59 for tumours of diameter 5, 15 and 35 mm, respectively. We
also study the probability of having latent/dormant metastases at detection of
the primary tumour, estimating that 33% of patients in our study had such
metastases.
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Affiliation(s)
- Alessandro Gasparini
- Alessandro Gasparini, Department of Medical
Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-17177,
Stockholm, Sweden.
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Isheden G, Grassmann F, Czene K, Humphreys K. Lymph node metastases in breast cancer: Investigating associations with tumor characteristics, molecular subtypes and polygenic risk score using a continuous growth model. Int J Cancer 2021; 149:1348-1357. [PMID: 34097750 DOI: 10.1002/ijc.33704] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/30/2021] [Accepted: 05/19/2021] [Indexed: 11/09/2022]
Abstract
We investigate the association between rate of breast cancer lymph node spread and grade, estrogen receptor (ER) status, progesteron receptor status, decision tree derived PAM50 molecular subtype and a polygenic risk score (PRS), using data on 10 950 women included from two different data sources. Lymph node spread was analyzed using a novel continuous tumor progression model that adjusts for tumor volume in a biologically motivated way and that incorporates covariates of interest. Grades 2 and 3 tumors, respectively, were associated with 1.63 and 2.17 times faster rates of lymph node spread than Grade 1 tumors (P < 10-16 ). ER/PR negative breast cancer was associated with a 1.25/1.19 times faster spread than ER/PR positive breast cancer, respectively (P = .0011 and .0012). Among the molecular subtypes luminal A, luminal B, Her2-enriched and basal-like, Her2-enriched breast cancer was associated with 1.53 times faster spread than luminal A cancer (P = .00072). PRS was not associated with the rate of lymph node spread. Continuous growth models are useful for quantifying associations between lymph node spread and tumor characteristics. These may be useful for building realistic progression models for microsimulation studies used to design individualized screening programs.
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Affiliation(s)
- Gabriel Isheden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Felix Grassmann
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,The Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK
| | - Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Keith Humphreys
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Timbres J, Moss C, Mera A, Haire A, Gillett C, Van Hemelrijck M, Sawyer E. Survival Outcomes in Invasive Lobular Carcinoma Compared to Oestrogen Receptor-Positive Invasive Ductal Carcinoma. Cancers (Basel) 2021; 13:cancers13123036. [PMID: 34207042 PMCID: PMC8234044 DOI: 10.3390/cancers13123036] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/19/2021] [Accepted: 06/07/2021] [Indexed: 01/19/2023] Open
Abstract
Invasive lobular breast cancer (ILC) accounts for 10-15% of breast cancers and has distinct characteristics compared with the more common invasive ductal carcinoma (IDC). Studies have shown that ILC may be less sensitive to chemotherapy than IDC, with lower rates of complete pathological response after neo-adjuvant chemotherapy, but it is not clear how this affects long-term survival. Patients at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2016 diagnosed with ER+ IDC or ER+ ILC were eligible for inclusion. Kaplan-Meier plots and Cox proportional-hazards regression models were used for analysis. There was no difference in overall survival comparing ER+ ILC to ER+ IDC (OR: 0.94, 95% CI: 0.83, 1.04) with a median follow-up time of 8.3 years compared to 8.4 years in IDC. However, ER+HER2- ILC had worse survival compared to ER+HER2- IDC in those that received chemotherapy (OR: 1.46, 95% CI: 1.06, 2.01). Here, median follow-up time was 7.0 years in ILC compared to 8.1 years in IDC. These results indicate worse overall survival after chemotherapy (neo-adjuvant and adjuvant) in ILC compared to ER+HER2- IDC even when correcting for tumour grade, age, size, and nodal involvement, but validation is needed in a larger study population.
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Affiliation(s)
- Jasmine Timbres
- Breast Cancer Genetics, King’s College London, London SE1 9RT, UK;
- Correspondence:
| | - Charlotte Moss
- Translational Oncology and Urology Research, King’s College London, London SE1 9RT, UK; (C.M.); (A.H.); (M.V.H.)
| | - Anca Mera
- Guy’s & St. Thomas’ Hospital, London SE1 9RT, UK;
| | - Anna Haire
- Translational Oncology and Urology Research, King’s College London, London SE1 9RT, UK; (C.M.); (A.H.); (M.V.H.)
| | - Cheryl Gillett
- KHP Cancer Biobank, King’s College London, London SE1 9RT, UK;
| | - Mieke Van Hemelrijck
- Translational Oncology and Urology Research, King’s College London, London SE1 9RT, UK; (C.M.); (A.H.); (M.V.H.)
| | - Elinor Sawyer
- Breast Cancer Genetics, King’s College London, London SE1 9RT, UK;
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10
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Suman M, Dugué PA, Wong EM, Joo JE, Hopper JL, Nguyen-Dumont T, Giles GG, Milne RL, McLean C, Southey MC. Association of variably methylated tumour DNA regions with overall survival for invasive lobular breast cancer. Clin Epigenetics 2021; 13:11. [PMID: 33461604 PMCID: PMC7814464 DOI: 10.1186/s13148-020-00975-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 11/10/2020] [Indexed: 12/12/2022] Open
Abstract
Background Tumour DNA methylation profiling has shown potential to refine disease subtyping and improve the diagnosis and prognosis prediction of breast cancer. However, limited data exist regarding invasive lobular breast cancer (ILBC). Here, we investigated the genome-wide variability of DNA methylation levels across ILBC tumours and assessed the association between methylation levels at the variably methylated regions and overall survival in women with ILBC. Methods Tumour-enriched DNA was prepared by macrodissecting formalin-fixed paraffin embedded (FFPE) tumour tissue from 130 ILBCs diagnosed in the participants of the Melbourne Collaborative Cohort Study (MCCS). Genome-wide tumour DNA methylation was measured using the HumanMethylation 450K (HM450K) BeadChip array. Variably methylated regions (VMRs) were identified using the DMRcate package in R. Cox proportional hazards regression models were used to assess the association between methylation levels at the ten most significant VMRs and overall survival. Gene set enrichment analyses were undertaken using the web-based tool Metaspace. Replication of the VMR and survival analysis findings was examined using data retrieved from The Cancer Genome Atlas (TCGA) for 168 ILBC cases. We also examined the correlation between methylation and gene expression for the ten VMRs of interest using TCGA data. Results We identified 2771 VMRs (P < 10−8) in ILBC tumours. The ten most variably methylated clusters were predominantly located in the promoter region of the genes: ISM1, APC, TMEM101, ASCL2, NKX6, HIST3H2A/HIST3H2BB, HCG4P3, HES5, CELF2 and EFCAB4B. Higher methylation level at several of these VMRs showed an association with reduced overall survival in the MCCS. In TCGA, all associations were in the same direction, however stronger than in the MCCS. The pooled analysis of the MCCS and TCGA data showed that methylation at four of the ten genes was associated with reduced overall survival, independently of age and tumour stage; APC: Hazard Ratio (95% Confidence interval) per one-unit M-value increase: 1.18 (1.02–1.36), TMEM101: 1.23 (1.02–1.48), HCG4P3: 1.37 (1.05–1.79) and CELF2: 1.21 (1.02–1.43). A negative correlation was observed between methylation and gene expression for CELF2 (R = − 0.25, P = 0.001), but not for TMEM101 and APC. Conclusions Our study identified regions showing greatest variability across the ILBC tumour genome and found methylation at several genes to potentially serve as a biomarker of survival for women with ILBC.
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Affiliation(s)
- Medha Suman
- Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, 3010, Australia.,Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia
| | - Pierre-Antoine Dugué
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.,Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.,Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
| | - Ee Ming Wong
- Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, 3010, Australia.,Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia
| | - JiHoon Eric Joo
- Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, 3010, Australia
| | - John L Hopper
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.,Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
| | - Tu Nguyen-Dumont
- Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, 3010, Australia.,Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia
| | - Graham G Giles
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.,Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.,Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
| | - Roger L Milne
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia.,Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.,Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia
| | - Catriona McLean
- Anatomical Pathology, Alfred Health, The Alfred Hospital, Melbourne, VIC, 3181, Australia
| | - Melissa C Southey
- Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, 3010, Australia. .,Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, 3168, Australia. .,Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia.
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11
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Erić I, Petek Erić A, Koprivčić I, Babić M, Pačarić S, Trogrlić B. Independent factors FOR poor prognosis in young patients with stage I-III breast cancer. Acta Clin Croat 2020; 59:242-251. [PMID: 33456111 PMCID: PMC7808215 DOI: 10.20471/acc.2020.59.02.07] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Breast cancer is the most common malignancy in the population of women under 40 years of age. Young age is an independent factor for poor prognosis. In this research, we tried to establish other factors for poor prognosis in stage I-III breast cancer. The following parameters were observed: tumor size, lymph node status, histologic grade, hormonal receptor status, Ki-67 prognostic index, Her2 neu status, histologic type of the tumor, local recurrence and metastases. Logistic regression was used to evaluate the effect of specific factors on the probability of lethal outcome and development of distant metastases. Our patients showed a predominance of T1 tumor (49.4%), had positive lymph nodes (62%) and most of them were pN1 (61.2%). Up to one-third of patients had triple negative status. Ki-67 proliferation index was high (25%). Multicentric tumor was detected in 23% of patients. There was no difference in overall survival between the two types of surgical procedures. Patients with pN0 status had better overall survival. Breast cancer in the population of young women has a more aggressive nature. Study results indicated positive lymph node status as an independent factor for poor prognosis of stage I-III breast cancer.
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Affiliation(s)
| | - Anamarija Petek Erić
- 1Josip Juraj Strossmayer University in Osijek, Faculty of Medicine, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
| | - Ivan Koprivčić
- 1Josip Juraj Strossmayer University in Osijek, Faculty of Medicine, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
| | - Marko Babić
- 1Josip Juraj Strossmayer University in Osijek, Faculty of Medicine, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
| | - Stana Pačarić
- 1Josip Juraj Strossmayer University in Osijek, Faculty of Medicine, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
| | - Bojan Trogrlić
- 1Josip Juraj Strossmayer University in Osijek, Faculty of Medicine, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
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12
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Dianatinasab M, Fararouei M, Daneshi N, Rezaian S, Mohammadianpanah M, Chaman R, Ghiasvand R. Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case-control study. Int J Cancer 2019; 145:2917-2925. [PMID: 30719718 DOI: 10.1002/ijc.32182] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 12/21/2018] [Accepted: 01/16/2019] [Indexed: 12/13/2022]
Abstract
Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours.
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Affiliation(s)
- Mostafa Dianatinasab
- Department of Epidemiology, Faculty of Public Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Fararouei
- Department of Epidemiology, Faculty of Public Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nima Daneshi
- Behbahan Faculty of Medical Sciences, Behbahan, Iran
| | - Shahab Rezaian
- Research Center for Environmental Determinants of Health (RCEDH), School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Reza Chaman
- Center for Health Related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Reza Ghiasvand
- Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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13
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Isheden G, Abrahamsson L, Andersson T, Czene K, Humphreys K. Joint models of tumour size and lymph node spread for incident breast cancer cases in the presence of screening. Stat Methods Med Res 2019; 28:3822-3842. [PMID: 30606087 PMCID: PMC6745622 DOI: 10.1177/0962280218819568] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Continuous growth models show great potential for analysing cancer screening
data. We recently described such a model for studying breast cancer tumour
growth based on modelling tumour size at diagnosis, as a function of screening
history, detection mode, and relevant patient characteristics. In this article,
we describe how the approach can be extended to jointly model tumour size and
number of lymph node metastases at diagnosis. We propose a new class of lymph
node spread models which are biologically motivated and describe how they can be
extended to incorporate random effects to allow for heterogeneity in underlying
rates of spread. Our final model provides a dramatically better fit to empirical
data on 1860 incident breast cancer cases than models in current use. We
validate our lymph node spread model on an independent data set consisting of
3961 women diagnosed with invasive breast cancer.
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Affiliation(s)
- Gabriel Isheden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
| | - Linda Abrahamsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
| | - Therese Andersson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
| | - Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
| | - Keith Humphreys
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
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14
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Fararouei M, Iqbal A, Rezaian S, Gheibi Z, Dianatinasab A, Shakarami S, Dianatinasab M. Dietary Habits and Physical Activity are Associated With the Risk of Breast Cancer Among Young Iranian Women: A Case-control Study on 1010 Premenopausal Women. Clin Breast Cancer 2018; 19:e127-e134. [PMID: 30503310 DOI: 10.1016/j.clbc.2018.10.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/26/2018] [Accepted: 10/26/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several studies conducted in developed countries introduced diet and physical inactivity as major risk factors for several types of cancers. However, the impact of diet and physical inactivity on the risk of breast cancer (BC) is understudied, and the limited findings are controversial. In addition, no or limited knowledge is available from the developing world. PATIENTS AND METHODS This case-control study was performed from November 2014 to March 2016 on 1010 young women aged 20 to 50 years who were newly diagnosed with BC. Data was obtained via a validated questionnaire and the global physical activity questionnaire (GPAQ2). Also, patients' medical and histopathology reports were reviewed. RESULTS The results of multiple logistic regression suggested that, except for the common risk factors for BC (older marital age, family history of BC, smoking, and being a passive smoker), eating red meat (adjusted odds ratio [aOR] >8 portions/week [p/w] vs. 0-2 p/w, 1.15; 95% confidence interval [CI], 1.04-1.28); eating fish (aOR >8 p/w vs. 0-2 p/w, 1.55; 95% CI, 1.12-2.76), fruit consumption (aOR 0-4 p/w vs. >8 p/w, 1.96; 95% CI, 1.07-3.82), pickle consumption (aOR >8 p/w vs. 7-8 p/w, 1.46; 95% CI, 1.31-1.70), and intensity of physical activity (aOR light vs. vigorous, 1.68; 95% CI, 1.47-1.98) were directly associated with a higher risk of BC in young women. CONCLUSION Our study supported the hypothesis that unhealthy dietary habits and physical inactivity are risk factors for BC. We found that a healthy diet containing low fat and high fruits and vegetables with regular exercise are effective ways to reduce the risk of BC among young women.
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Affiliation(s)
- Mohammad Fararouei
- Department of Epidemiology, Faculty of Public Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Aqsa Iqbal
- Physiology and Biophysics Department, University of Illinois at Chicago, Chicago, IL
| | - Shahab Rezaian
- Research Center for Environmental Determinants of Health (RCEDH), School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zahra Gheibi
- Department of Epidemiology, Faculty of Public Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Aria Dianatinasab
- Department of Biochemistry, Student research committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saba Shakarami
- Center for Health Related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Mostafa Dianatinasab
- Bahar Center for Education, Research and Treatment, Shahroud University of Medical Sciences, Shahroud, Iran.
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15
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Erić I, Petek Erić A, Kristek J, Koprivčić I, Babić M. BREAST CANCER IN YOUNG WOMEN: PATHOLOGIC AND IMMUNOHISTOCHEMICAL FEATURES. Acta Clin Croat 2018; 57:497-502. [PMID: 31168183 PMCID: PMC6536281 DOI: 10.20471/acc.2018.57.03.13] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
SUMMARY – A young woman with breast cancer is considered to be a woman younger than 40. According to the literature, breast cancer in the population of young women usually is of a higher histologic grade, unfavorable hormonal status, and overall higher mortality rate when compared with breast cancer occurring in older population. We compared pathologic and immunohistochemical features of breast carcinoma in women under 40 years of age with the respective features in women over 60 years of age. The following parameters were observed in these two groups: tumor size, lymph node status, histologic grade, hormonal receptor status, Ki-67 prognostic index, Her2/neu status, and histologic type of the tumor. Early onset breast carcinoma was found to have a higher frequency of tumor grade 3 (29% vs. 17%) and estrogen receptor negativity (45% vs. 23%). In the group of young women, breast carcinoma was mostly multicentric (23% vs. 5%), triple-negative (32% vs. 10%), and was found to have higher proliferation index Ki-67 (25% vs. 10%). Our results confirmed differences between the young and older groups of patients. In the group of young women, we found predominantly unfavorable prognostic parameters of the disease.
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Affiliation(s)
| | - Anamarija Petek Erić
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
| | - Jozo Kristek
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
| | - Ivan Koprivčić
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
| | - Marko Babić
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Osijek University Hospital Centre, Osijek, Croatia
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16
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Sandvei MS, Vatten LJ, Bjelland EK, Eskild A, Hofvind S, Ursin G, Opdahl S. Menopausal hormone therapy and breast cancer risk: effect modification by body mass through life. Eur J Epidemiol 2018; 34:267-278. [DOI: 10.1007/s10654-018-0431-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 07/27/2018] [Indexed: 12/28/2022]
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17
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Horne HN, Oh H, Sherman ME, Palakal M, Hewitt SM, Schmidt MK, Milne RL, Hardisson D, Benitez J, Blomqvist C, Bolla MK, Brenner H, Chang-Claude J, Cora R, Couch FJ, Cuk K, Devilee P, Easton DF, Eccles DM, Eilber U, Hartikainen JM, Heikkilä P, Holleczek B, Hooning MJ, Jones M, Keeman R, Mannermaa A, Martens JWM, Muranen TA, Nevanlinna H, Olson JE, Orr N, Perez JIA, Pharoah PDP, Ruddy KJ, Saum KU, Schoemaker MJ, Seynaeve C, Sironen R, Smit VTHBM, Swerdlow AJ, Tengström M, Thomas AS, Timmermans AM, Tollenaar RAEM, Troester MA, van Asperen CJ, van Deurzen CHM, Van Leeuwen FF, Van't Veer LJ, García-Closas M, Figueroa JD. E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium. Sci Rep 2018; 8:6574. [PMID: 29700408 PMCID: PMC5920115 DOI: 10.1038/s41598-018-23733-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 03/16/2018] [Indexed: 01/20/2023] Open
Abstract
E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score < 100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97-1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06-2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.
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Affiliation(s)
- Hisani N Horne
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Division of Molecular Genetics & Pathology, US Food and Drug Administration, Silver Spring, MD, USA
| | - Hannah Oh
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Department of Health Policy and Management, College of Health Science, Korea University, Seoul, Korea
| | - Mark E Sherman
- Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA
| | - Maya Palakal
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Stephen M Hewitt
- Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Marjanka K Schmidt
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands
| | - Roger L Milne
- Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Victoria, Australia
| | - David Hardisson
- Department of Pathology, Molecular Pathology and Therapeutic Targets Group, Hospital Universitario La Paz IdiPAZ, and Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain
| | - Javier Benitez
- Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain
- Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
| | - Carl Blomqvist
- Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Manjeet K Bolla
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Research Group Genetic Cancer Epidemiology, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Renata Cora
- Independent contractor, CT(ASCP), MB (ASCP), National Cancer Institute, Bethesda, MD, USA
| | - Fergus J Couch
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Katarina Cuk
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Peter Devilee
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
| | - Douglas F Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Diana M Eccles
- Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Ursula Eilber
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jaana M Hartikainen
- Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland
- Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland
| | - Päivi Heikkilä
- Department of Pathology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | | | - Maartje J Hooning
- Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Michael Jones
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
| | - Renske Keeman
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Arto Mannermaa
- Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland
- Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland
| | - John W M Martens
- Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Taru A Muranen
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Heli Nevanlinna
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Janet E Olson
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Nick Orr
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
| | - Jose I A Perez
- Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain
| | - Paul D P Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | | | - Kai-Uwe Saum
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Minouk J Schoemaker
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
| | - Caroline Seynaeve
- Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Reijo Sironen
- Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland
- Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland
- Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland
| | - Vincent T H B M Smit
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
| | - Anthony J Swerdlow
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
- Division of Breast Cancer Research, The Institute of Cancer Research, London, UK
| | - Maria Tengström
- Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland
- Cancer Center, Kuopio University Hospital, Kuopio, Finland
- Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland
| | - Abigail S Thomas
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - A Mieke Timmermans
- Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Rob A E M Tollenaar
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Melissa A Troester
- Department of Pathology and Laboratory Medicin, Gillings School of Global Public Health, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Christi J van Asperen
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Flora F Van Leeuwen
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Laura J Van't Veer
- Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | | | - Jonine D Figueroa
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
- Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK.
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18
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Isheden G, Humphreys K. Modelling breast cancer tumour growth for a stable disease population. Stat Methods Med Res 2017; 28:681-702. [DOI: 10.1177/0962280217734583] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.
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Affiliation(s)
- Gabriel Isheden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
| | - Keith Humphreys
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
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19
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Morselli E, Santos RS, Criollo A, Nelson MD, Palmer BF, Clegg DJ. The effects of oestrogens and their receptors on cardiometabolic health. Nat Rev Endocrinol 2017; 13:352-364. [PMID: 28304393 DOI: 10.1038/nrendo.2017.12] [Citation(s) in RCA: 124] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Cardiovascular disease (CVD) is one of the leading causes of mortality in developed countries. The incidence of CVD is sexually dimorphic, and research has focused on the contribution of sex steroids to the development and progression of the cardiometabolic syndrome, which is defined as a clustering of interrelated risk factors that promote the development of atherosclerosis (which can lead to CVD) and type 2 diabetes mellitus. Data are inconclusive as to how sex steroids and their respective receptors increase or suppress the risk of developing the cardiometabolic syndrome and thus CVD. In this Review, we discuss the potential role, or roles, of sex hormones in cardiometabolic health by first focusing on the influence of oestrogens and their receptors on the risk of developing cardiometabolic syndrome and CVD. We also highlight what is known about testosterone and its potential role in protecting against the development of the cardiometabolic syndrome and CVD. Given the inconclusive nature of the data regarding the direct effects of each sex hormone, we advocate and highlight the importance of studying the relative levels and the ratio of sex hormones to each other, as well as the use of cross sex hormone therapy and its effect on cardiometabolic health.
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Affiliation(s)
- Eugenia Morselli
- Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
| | - Roberta S Santos
- Obesity and Comorbidities Research Center, Institute of Biology, State University of Campinas, Campinas 1, 3083-864, Brazil
- Cedars-Sinai Diabetes and Obesity Research Institute, Department of Biomedical Research, Los Angeles, California 90048, USA
| | - Alfredo Criollo
- Advanced Center for Chronic Diseases (ACCDiS) and Center for Molecular Studies of the Cell (CEMC), Santiago 8380000, Chile
- Instituto de Investigación en Ciencias Odontológicas (ICOD), Facultad de Odontología, Universidad de Chile, Santiago 8380492, Chile
| | - Michael D Nelson
- Applied Physiology and Advanced Imaging Laboratory, Department of Kinesiology, University of Texas at Arlington, Texas 76019, USA
| | - Biff F Palmer
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
| | - Deborah J Clegg
- Cedars-Sinai Diabetes and Obesity Research Institute, Department of Biomedical Research, Los Angeles, California 90048, USA
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20
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Labrie F, Martel C. A low dose (6.5 mg) of intravaginal DHEA permits a strictly local action while maintaining all serum estrogens or androgens as well as their metabolites within normal values. Horm Mol Biol Clin Investig 2017; 29:39-60. [PMID: 27997350 DOI: 10.1515/hmbci-2016-0042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 10/28/2016] [Indexed: 01/28/2023]
Abstract
OBJECTIVE Serum concentrations of estradiol (E2) and testosterone (testo) measured by mass spectrometry-based assays should remain below the 95th centile measured at 9.3 pg/mL for E2 and 0.26 ng/mL for testo in normal postmenopausal women in order to avoid the risk of non-physiological systemic exposure to elevated serum concentrations of these two sex steroids. METHODS Serum E2 and testo, as well as dehydroepiandrosterone (DHEA) and nine of its other metabolites, were measured at 10 time intervals over 24 h on the first and seventh days of daily intravaginal administration of 0.50% (6.5 mg) DHEA by validated mass spectrometry-based assays. RESULTS No biologically significant change in the individual serum concentrations of E2, testo or DHEA was observed. Most importantly, estrone sulfate (E1-S) and the glucuronidated androgen metabolites also remained within normal values, thus confirming the absence of biologically significant systemic exposure in line with intracrinology. Using data from the literature, comparison is made with serum E2 above normal postmenopausal values following administration of 10-μg E2 tablets. CONCLUSION While the clinical program on vulvovaginal atrophy has shown the efficacy and safety of intravaginal 6.5 mg of DHEA (prasterone), the present data illustrate in detail the serum levels of the individual sex steroids and their metabolites derived from DHEA. The data obtained are in line with the physiology of intracrinology and confirm an action limited to the vagina as the serum concentrations of all sex steroids are maintained within the normal values of menopause, thus protecting the uterus and most likely other tissues.
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Jones ME, Schoemaker MJ, Wright L, McFadden E, Griffin J, Thomas D, Hemming J, Wright K, Ashworth A, Swerdlow AJ. Menopausal hormone therapy and breast cancer: what is the true size of the increased risk? Br J Cancer 2016; 115:607-15. [PMID: 27467055 PMCID: PMC4997554 DOI: 10.1038/bjc.2016.231] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 06/30/2016] [Accepted: 07/06/2016] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Menopausal hormone therapy (MHT) increases breast cancer risk; however, most cohort studies omit MHT use after enrolment and many infer menopausal age. METHODS We used information from serial questionnaires from the UK Generations Study cohort to estimate hazard ratios (HRs) for breast cancer among post-menopausal women with known menopausal age, and examined biases induced when not updating data on MHT use and including women with inferred menopausal age. RESULTS Among women recruited in 2003-2009, at 6 years of follow-up, 58 148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39 183 women with known menopausal age, 775 developed breast cancer, and the HR in relation to current oestrogen plus progestogen MHT use (based on 52 current oestrogen plus progestogen MHT users in breast cancer cases) relative to those with no previous MHT use was 2.74 (95% confidence interval (CI): 2.05-3.65) for a median duration of 5.4 years of current use, reaching 3.27 (95% CI: 1.53-6.99) at 15+ years of use. The excess HR was underestimated by 53% if oestrogen plus progestogen MHT use was not updated after recruitment, 13% if women with uncertain menopausal age were included, and 59% if both applied. The HR for oestrogen-only MHT was not increased (HR=1.00; 95% CI: 0.66-1.54). CONCLUSIONS Lack of updating MHT status through follow-up and inclusion of women with inferred menopausal age is likely to result in substantial underestimation of the excess relative risks for oestrogen plus progestogen MHT use in studies with long follow-up, limited updating of exposures, and changing or short durations of use.
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Affiliation(s)
- Michael E Jones
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
| | - Minouk J Schoemaker
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
| | - Lauren Wright
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
| | - Emily McFadden
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
| | - James Griffin
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
| | - Dawn Thomas
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
| | - Jane Hemming
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
| | - Karen Wright
- The National Cancer Registration Service–Eastern Office, Public Health England, Cambridge CB21 5XA, UK
| | - Alan Ashworth
- Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK
- Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London SW7 3RP, UK
- Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK
| | - Anthony J Swerdlow
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
- Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK
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Román M, Graff-Iversen S, Weiderpass E, Vangen S, Sakshaug S, Hofvind S, Ursin G. Postmenopausal Hormone Therapy and Breast Cancer Prognostic Characteristics: A Linkage between Nationwide Registries. Cancer Epidemiol Biomarkers Prev 2016; 25:1464-1473. [PMID: 27461048 DOI: 10.1158/1055-9965.epi-16-0240] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Accepted: 07/16/2016] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The effects of use of different types of hormone therapy on breast cancer risk according to prognostic factors are largely unknown. METHODS We linked data from the Norwegian Prescription Database and the Cancer Registry of Norway during 2004 to 2009 on all women ages 45 to 79 years (N = 686,614). We estimated rate ratios and 95% confidence intervals for breast cancer in relation to hormone therapy using Poisson regression. RESULTS During an average 4.8 years of follow-up, 7,910 invasive breast cancers were diagnosed. Compared with nonusers of hormone therapy, users of estradiol and tibolone were more likely to be diagnosed with grade I, lymph node-negative, and estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+) tumors. However, compared with nonusers, users of the most common estrogen and progestin combinations [estradiol-norethisterone acetate (NETA) preparations (Kliogest, Activelle or Trisekvens)] were at a 4- to 5-fold elevated risk of grade I tumors, 3-fold elevated risk of lymph node-negative tumors, and 3- to 4-fold elevated risk of ER+/PR+ tumors. Importantly, estradiol-NETA users were also at a 2- to 3-fold increased risk of medium differentiated (grade II) tumors and tumors with lymph node involvement. CONCLUSIONS Use of oral estradiol, tibolone, and estradiol-NETA predominantly increases the risk of breast cancer with favorable prognosis characteristics. However, use of estradiol-NETA preparations also increases the risk of breast cancers with less favorable characteristics. IMPACT The hormone therapy preparations most commonly used in the Nordic countries are associated with both breast cancers with good and less favorable prognosis characteristics. Cancer Epidemiol Biomarkers Prev; 25(11); 1464-73. ©2016 AACR.
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Affiliation(s)
- Marta Román
- Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.,Women and Children's Division, National Advisory Unit for Women's Health, Oslo University Hospital, Oslo, Norway
| | - Sidsel Graff-Iversen
- Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway.,Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Elisabete Weiderpass
- Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.,Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland
| | - Siri Vangen
- Women and Children's Division, National Advisory Unit for Women's Health, Oslo University Hospital, Oslo, Norway
| | - Solveig Sakshaug
- Department of Pharmacoepidemiology, Norwegian Institute of Public Health, Oslo, Norway
| | - Solveig Hofvind
- Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.,Oslo and Akershus University College of Applied Sciences, Faculty of Health Science, Oslo, Norway
| | - Giske Ursin
- Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. .,Department of Preventive Medicine, University of Southern California, California.,Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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23
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Park B, Choi JY, Sung HK, Ahn C, Hwang Y, Jang J, Lee J, Kim H, Shin HR, Park S, Han W, Noh DY, Yoo KY, Kang D, Park SK. Attribution to Heterogeneous Risk Factors for Breast Cancer Subtypes Based on Hormone Receptor and Human Epidermal Growth Factor 2 Receptor Expression in Korea. Medicine (Baltimore) 2016; 95:e3063. [PMID: 27057831 PMCID: PMC4998747 DOI: 10.1097/md.0000000000003063] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
We conducted a heterogeneous risk assessment of breast cancer based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) calculating the risks and population-based attributable fractions (PAFs) for modifiable and nonmodifiable factors.Using matched case-control study design from the Seoul Breast Cancer Study and the national prevalence of exposure, the risks and PAFs for modifiable and nonmodifiable factors were estimated for total breast cancers and subtypes.The attribution to modifiable factors was different for each subtype (luminal A, PAF = 61.4% [95% confidence interval, CI = 54.3%-69.8%]; luminal B, 21.4% [95% CI = 18.6-24.9%]; HER2-overexpression, 59.4% [95% CI = 47.8%-74.3%], and triple negative tumors [TNs], 27.1% [95% CI = 22.9%-32.4%)], and the attribution to the modifiable factors for the luminal A and HER2-overexpression subtypes was higher than that of the luminal B and TN subtypes (P heterogeneity ≤ 0.001). The contribution of modifiable reproductive factors to luminal A type in premenopausal women was higher than that of the other subtypes (18.2% for luminal A; 3.1%, 8.1%, and -3.1% for luminal B, HER2-overexpression, and TN subtypes, respectively; P heterogeneity ≤ 0.001). Physical activity had the highest impact preventing 32.6% of luminal A, 14.5% of luminal B, 38.0% of HER2-overexpression, and 26.9% of TN subtypes (P heterogeneity = 0.014). Total reproductive factors were also heterogeneously attributed to each breast cancer subtype (luminal A, 65.4%; luminal B, 24.1%; HER2-overexpression, 57.9%, and TN subtypes, -3.1%; P heterogeneity ≤ 0.001).Each pathological subtype of breast cancer by HRs and HER2 status may be associated with heterogeneous risk factors and their attributable risk, suggesting a different etiology. The luminal B and TN subtypes seemed to be less preventable despite intervention for alleged risk factors, even though physical activity had a high preventable potential against breast cancer.
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Affiliation(s)
- Boyoung Park
- From the Graduate School of Cancer Science and Policy, National Cancer Center (BP); Department of Preventive Medicine, Seoul National University College of Medicine (J-YC, HKS, CA, YH, JJ, JL, HK, K-YY, DK, SKP); Cancer Research Center (J-YC, CA, YH, JJ, JL, HK, DK, SKP); Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea (J-YC, HKS, CA, YH, JJ, JL, HK, DK, SKP); Western Pacific Regional Office, World Health Organization, Manila, Philippines (H-RS); Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University (SP); and Department of Surgery, Seoul National University Hospital and College of Medicine (WH-D-YN), Seoul, Korea
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24
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Al-Saqi SH, Jonasson AF, Naessén T, Uvnäs-Moberg K. Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women. Post Reprod Health 2016; 22:25-33. [PMID: 26883689 DOI: 10.1177/2053369116629042] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
OBJECTIVE To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. STUDY DESIGN Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks. RESULTS The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04). CONCLUSION Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.
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Affiliation(s)
- Shahla Hamza Al-Saqi
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Aino Fianu Jonasson
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Tord Naessén
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Kerstin Uvnäs-Moberg
- Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden School of Life Science, University of Skövde, Skövde, Sweden
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25
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Dartois L, Fagherazzi G, Baglietto L, Boutron-Ruault MC, Delaloge S, Mesrine S, Clavel-Chapelon F. Proportion of premenopausal and postmenopausal breast cancers attributable to known risk factors: Estimates from the E3N-EPIC cohort. Int J Cancer 2016; 138:2415-27. [DOI: 10.1002/ijc.29987] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Accepted: 12/10/2015] [Indexed: 11/06/2022]
Affiliation(s)
- Laureen Dartois
- Inserm (Institut National De La Santé Et De La Recherche Médical), Centre for Research in Epidemiology and Population Health (CESP); U1018, Team 9 Villejuif F-94805 France
- Université Paris-Sud; UMRS 1018 Villejuif F-94805 France
- Gustave Roussy; Villejuif F-94805 France
| | - Guy Fagherazzi
- Inserm (Institut National De La Santé Et De La Recherche Médical), Centre for Research in Epidemiology and Population Health (CESP); U1018, Team 9 Villejuif F-94805 France
- Université Paris-Sud; UMRS 1018 Villejuif F-94805 France
- Gustave Roussy; Villejuif F-94805 France
| | - Laura Baglietto
- Cancer Epidemiology Centre, Cancer Council of Victoria; Melbourne, Victoria Australia
- Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health; University of Melbourne; Victoria Australia
| | - Marie-Christine Boutron-Ruault
- Inserm (Institut National De La Santé Et De La Recherche Médical), Centre for Research in Epidemiology and Population Health (CESP); U1018, Team 9 Villejuif F-94805 France
- Université Paris-Sud; UMRS 1018 Villejuif F-94805 France
- Gustave Roussy; Villejuif F-94805 France
| | - Suzette Delaloge
- Department of Medical Oncology; Gustave Roussy; Villejuif F-94805 France
| | - Sylvie Mesrine
- Inserm (Institut National De La Santé Et De La Recherche Médical), Centre for Research in Epidemiology and Population Health (CESP); U1018, Team 9 Villejuif F-94805 France
- Université Paris-Sud; UMRS 1018 Villejuif F-94805 France
- Gustave Roussy; Villejuif F-94805 France
| | - Françoise Clavel-Chapelon
- Inserm (Institut National De La Santé Et De La Recherche Médical), Centre for Research in Epidemiology and Population Health (CESP); U1018, Team 9 Villejuif F-94805 France
- Université Paris-Sud; UMRS 1018 Villejuif F-94805 France
- Gustave Roussy; Villejuif F-94805 France
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26
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Abstract
The limitations of mammography in the detection and evaluation of invasive lobular carcinoma (ILC) have long been recognized, presenting real clinical challenges in treatment planning for these tumors. However, advances in mammography, ultrasound, and magnetic resonance imaging present opportunities to improve the diagnosis and preoperative assessment of ILC. The evidence supporting the performance of each imaging modality will be reviewed, specifically as it relates to the pathology of ILC and its subtypes. Further, we will discuss emerging technologies that may be employed to enhance the detection rate and ultimately result in more effective screening and staging of ILC.
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Affiliation(s)
- Karen Johnson
- Duke Cancer Institute, Duke University Medical Center, 20 Medicine Circle, Durham, NC, 27710, USA
| | - Deba Sarma
- Duke Cancer Institute, Duke University Medical Center, 20 Medicine Circle, Durham, NC, 27710, USA
| | - E Shelley Hwang
- Duke Cancer Institute, Duke University Medical Center, 20 Medicine Circle, Durham, NC, 27710, USA.
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27
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Dossus L, Benusiglio PR. Lobular breast cancer: incidence and genetic and non-genetic risk factors. Breast Cancer Res 2015; 17:37. [PMID: 25848941 PMCID: PMC4357148 DOI: 10.1186/s13058-015-0546-7] [Citation(s) in RCA: 121] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2014] [Accepted: 03/03/2015] [Indexed: 12/12/2022] Open
Abstract
While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.
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28
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New Therapeutic Approaches for Invasive Lobular Carcinoma. CURRENT BREAST CANCER REPORTS 2014. [DOI: 10.1007/s12609-014-0158-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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29
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Samaras N, Papadopoulou MA, Samaras D, Ongaro F. Off-label use of hormones as an antiaging strategy: a review. Clin Interv Aging 2014; 9:1175-86. [PMID: 25092967 PMCID: PMC4116364 DOI: 10.2147/cia.s48918] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA) in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders, cardiovascular health and sexual activity. We also provide information on the efficiency and safety of hormone replacement protocols in aging patients. Finally, we argue on future perspectives of such protocols as part of everyday practice.
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Affiliation(s)
| | | | - Dimitrios Samaras
- Department of Medical Specialties, Clinical Nutrition, Geneva University Hospitals, Geneva, Switzerland
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30
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Li CI, Daling JR, Haugen KL, Tang MTC, Porter PL, Malone KE. Use of menopausal hormone therapy and risk of ductal and lobular breast cancer among women 55-74 years of age. Breast Cancer Res Treat 2014; 145:481-9. [PMID: 24748570 DOI: 10.1007/s10549-014-2960-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 04/07/2014] [Indexed: 11/30/2022]
Abstract
The Women's Health Initiative (WHI) randomized trials found that use of combined estrogen and progestin menopausal hormone therapy (CHT) increases breast cancer risk, but use of unopposed estrogen hormone therapy (EHT) does not. However, several questions regarding the impact of hormone use on risk of different types of breast cancer and what thresholds of use confer elevations in risk remain. We conducted a population-based case-control study among women 55-74 years of age to assess the association between menopausal hormone use and risk of invasive ductal and invasive lobular breast carcinomas. Associations were evaluated using polytomous logistic regression and analyses included 880 ductal cases, 1,027 lobular cases, and 856 controls. Current EHT and CHT use were associated with 1.6-fold [95 % confidence interval (CI): 1.1-2.2] and 2.3-fold (95 % CI: 1.7-3.2) increased risks of lobular breast cancer, respectively, but neither was associated with risk of ductal cancer. Lobular cancer risk was increased after 9 years of EHT use, but after only 3 years of CHT use. Evidence across more than a dozen studies indicates that lobular carcinoma is the type of breast cancer most strongly influenced by menopausal hormones. Here, we characterize what thresholds of duration of use of both EHT and CHT that confer elevations in risk. Despite the rapid decline in hormone therapy use the WHI results were published, study of the hazards associated with these medications remains relevant given the estimated 38 million hormone therapy prescriptions that are still filled in the United States annually.
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MESH Headings
- Aged
- Breast Neoplasms/chemically induced
- Breast Neoplasms/metabolism
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/chemically induced
- Carcinoma, Ductal, Breast/metabolism
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Lobular/chemically induced
- Carcinoma, Lobular/metabolism
- Carcinoma, Lobular/pathology
- Case-Control Studies
- Estrogen Replacement Therapy/adverse effects
- Estrogens/therapeutic use
- Female
- Hormone Replacement Therapy/adverse effects
- Humans
- Menopause
- Middle Aged
- Progestins/therapeutic use
- Receptors, Estrogen/metabolism
- Risk Assessment
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Affiliation(s)
- Christopher I Li
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,
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31
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Munsell MF, Sprague BL, Berry DA, Chisholm G, Trentham-Dietz A. Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev 2014; 36:114-36. [PMID: 24375928 PMCID: PMC3873844 DOI: 10.1093/epirev/mxt010] [Citation(s) in RCA: 271] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2013] [Indexed: 12/20/2022] Open
Abstract
To assess the joint relationships among body mass index, menopausal status, and breast cancer according to breast cancer subtype and estrogen-progestin medication use, we conducted a meta-analysis of 89 epidemiologic reports published in English during 1980-2012 identified through a systematic search of bibliographic databases. Pooled analysis yielded a summary risk ratio of 0.78 (95% confidence interval (CI): 0.67, 0.92) for hormone receptor-positive premenopausal breast cancer associated with obesity (body mass index (weight (kg)/height (m)(2)) ≥30 compared with <25). Obesity was associated with a summary risk ratio of 1.39 (95% CI: 1.14, 1.70) for receptor-positive postmenopausal breast cancer. For receptor-negative breast cancer, the summary risk ratios of 1.06 (95% CI: 0.70, 1.60) and 0.98 (95% CI: 0.78, 1.22) associated with obesity were null for both premenopausal and postmenopausal women, respectively. Elevated postmenopausal breast cancer risk ratios associated with obesity were limited to women who never took estrogen-progestin therapy, with risk ratios of 1.42 (95% CI: 1.30, 1.55) among never users and 1.18 (95% CI: 0.98, 1.42) among users; too few studies were available to examine this relationship according to receptor subtype. Future research is needed to confirm whether obesity is unrelated to receptor-negative breast cancer in populations of postmenopausal women with low prevalence of hormone medication use.
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Affiliation(s)
| | | | | | | | - Amy Trentham-Dietz
- Correspondence to Dr. Amy Trentham-Dietz, University of Wisconsin, 610 Walnut Street, WARF Room 307, Madison, WI 53726 (e-mail: )
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32
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Promestriene, a specific topic estrogen. Review of 40 years of vaginal atrophy treatment. Anticancer Drugs 2013; 24:989-98. [DOI: 10.1097/cad.0b013e328365288e] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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33
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Gierisch JM, Coeytaux RR, Urrutia RP, Havrilesky LJ, Moorman PG, Lowery WJ, Dinan M, McBroom AJ, Hasselblad V, Sanders GD, Myers ER. Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev 2013; 22:1931-43. [PMID: 24014598 DOI: 10.1158/1055-9965.epi-13-0298] [Citation(s) in RCA: 223] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Oral contraceptives may influence the risk of certain cancers. As part of the AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, we conducted a systematic review to estimate associations between oral contraceptive use and breast, cervical, colorectal, and endometrial cancer incidence. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews. Study inclusion criteria were women taking oral contraceptives for contraception or ovarian cancer prevention; includes comparison group with no oral contraceptive use; study reports quantitative associations between oral contraceptive exposure and relevant cancers; controlled study or pooled patient-level meta-analyses; sample size for nonrandomized studies ≥100; peer-reviewed, English-language; published from January 1, 2000 forward. Random-effects meta-analyses were conducted by estimating pooled ORs with 95% confidence intervals (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial cancers studies. Breast cancer incidence was slightly but significantly increased in users (OR, 1.08; CI, 1.00-1.17); results show a higher risk associated with more recent use of oral contraceptives. Risk of cervical cancer was increased with duration of oral contraceptive use in women with human papillomavirus infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86; CI, 0.79-0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43-0.77) were significantly reduced by oral contraceptive use. Compared with never use, ever use of oral contraceptives is significantly associated with decreases in colorectal and endometrial cancers and increases in breast cancers. Although elevated breast cancer risk was small, relatively high incidence of breast cancers means that oral contraceptives may contribute to a substantial number of cases.
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Affiliation(s)
- Jennifer M Gierisch
- Authors' Affiliations: Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center; Duke Evidence-Based Practice Center, Duke Clinical Research Institute; Departments of Medicine, Community and Family Medicine, Obstetrics and Gynecology, and Biostatistics and Bioinformatics, Duke University School of Medicine; Duke Cancer Institute, Duke University Health System; Duke Clinical Research Institute, Durham; and Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
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Nyante SJ, Dallal CM, Gierach GL, Park Y, Hollenbeck AR, Brinton LA. Risk factors for specific histopathological types of postmenopausal breast cancer in the NIH-AARP Diet and Health Study. Am J Epidemiol 2013; 178:359-71. [PMID: 23899816 DOI: 10.1093/aje/kws471] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Risk factor associations for rare breast cancer variants are often imprecise, obscuring differences between tumor types. To clarify differences, we examined risk factors for 5 histological types of breast cancer in the National Institutes of Health-AARP Diet and Health Study. Risk factor information was self-reported. We followed 192,076 postmenopausal women aged 50-71 years from 1995-1996 through 2006. During that time period, 5,334 ductal, 836 lobular, 639 mixed ductal-lobular, 216 mucinous, and 132 tubular breast cancers were diagnosed. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Heterogeneity was evaluated using case-only logistic regression. The strongest differences were for menopausal hormone therapy (Pheterogeneity < 0.01) and age at first birth (Pheterogeneity < 0.01). Risk of tubular cancer in relation to current menopausal hormone therapy (for current use vs. never use, hazard ratio (HR) = 4.39, 95% confidence interval (CI): 2.77, 6.96) was several times stronger than risk of other histological types (range of HRs, 1.39-1.75). Older age at first birth was unassociated with risk of mucinous (for ≥30 years vs. 20-24 years, HR = 0.62, 95% CI: 0.27, 1.42) or tubular (HR = 1.08, 95% CI: 0.51, 2.29) tumors, in contrast to clear positive associations with lobular (HR = 1.82, 95% CI: 1.39, 2.37) and mixed ductal-lobular (HR = 1.87, 95% CI: 1.39, 2.51) tumors. Differing associations for hormonal factors and mucinous and tubular cancers suggest etiologies distinct from those of common breast cancers.
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MESH Headings
- Adenocarcinoma/epidemiology
- Adenocarcinoma/pathology
- Adenocarcinoma, Mucinous/epidemiology
- Adenocarcinoma, Mucinous/pathology
- Aged
- Anthropometry
- Breast Neoplasms/epidemiology
- Breast Neoplasms/metabolism
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/epidemiology
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Lobular/epidemiology
- Carcinoma, Lobular/pathology
- Cohort Studies
- Confidence Intervals
- Contraceptives, Oral
- Female
- Follow-Up Studies
- Hormone Replacement Therapy/statistics & numerical data
- Humans
- Logistic Models
- Maternal Age
- Middle Aged
- National Institutes of Health (U.S.)
- Neoplasm Grading
- Neoplasm Staging
- Postmenopause/physiology
- Receptors, Estrogen/metabolism
- Receptors, Progesterone/metabolism
- Risk Factors
- Surveys and Questionnaires
- United States/epidemiology
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Affiliation(s)
- Sarah J Nyante
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room 7-E236, MSC 9774, Bethesda, MD 20892-9774, USA.
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Abrahamsson L, Humphreys K. A statistical model of breast cancer tumour growth with estimation of screening sensitivity as a function of mammographic density. Stat Methods Med Res 2013; 25:1620-37. [DOI: 10.1177/0962280213492843] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Understanding screening sensitivity and tumour progression is important for designing and evaluating screening programmes for breast cancer. Several approaches for estimating tumour growth rates have been described, some of which simultaneously estimate (mammography) screening sensitivity. None of the continuous tumour growth modelling approaches has incorporated mammographic density, although it is known to have a profound influence on mammographic screening sensitivity. We describe a new approach for estimating breast cancer tumour growth which builds on recently described continuous tumour growth models and estimates mammographic screening sensitivity as a function of tumour size and mammographic density.
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Affiliation(s)
- Linda Abrahamsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Keith Humphreys
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Zare N, Haem E, Lankarani KB, Heydari ST, Barooti E. Breast cancer risk factors in a defined population: weighted logistic regression approach for rare events. J Breast Cancer 2013; 16:214-219. [PMID: 23843856 PMCID: PMC3706869 DOI: 10.4048/jbc.2013.16.2.214] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 05/09/2013] [Indexed: 02/08/2023] Open
Abstract
PURPOSE This study aimed to determine out risk factors for female breast cancer in a low socioeconomic population in Iran. METHODS Between 2007 and 2009, a total of 25,592 women who were ensured by the Imam Khomeini Relief Foundation participated in this screening program. The characteristics of patients diagnosed with breast cancer (n=111) were compared with those of control cases (n=25,481). In this study, we used relogit analysis (rare event logistic regression) with a weighting method using program Zelig. RESULTS Of 25,592 women, 3.9/1,000 had breast cancer, from which 38 were diagnosed during screening and 73 had already been diagnosed. The mean and standard deviation of age in breast cancer patients and in healthy controls were 49.18±8.86 years and 46.65±9.40 years, respectively. The findings based on the multivariate model revealed that the past history of ovarian cancer, hormone therapy, and first relatives with breast cancer were associated with increased risk for breast cancer. However, the use of oral contraceptive pills was found to be associated with reduced risk for breast cancer. CONCLUSION Due to the rarity of the event in the population, relogit with a weighting method was used to investigate the major risk factors for breast cancer. These factors include oral contraceptive pill use, a history of ovarian cancer of the person under study, first relatives with breast cancer and hormone therapy.
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Affiliation(s)
- Najf Zare
- Department of Biostatistics, Research Center of Fertility and Infertility, Shiraz University of Medical Sciences School of Medicine, Shiraz, Iran
| | - Elham Haem
- Department of Biostatistics, Research Center of Fertility and Infertility, Shiraz University of Medical Sciences School of Medicine, Shiraz, Iran
| | - Kamran B. Lankarani
- Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyyed Taghi Heydari
- Department of Biostatistics, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Esmat Barooti
- Ministry of Health and Medical Education, Women's Affairs Office, Tehran, Iran
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Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, Hirunpat S, Woodtichartpreecha P, Boonlikit S, Teerawattananon Y, Thakkinstian A. Risk factors of breast cancer: a systematic review and meta-analysis. Asia Pac J Public Health 2013; 25:368-87. [PMID: 23709491 DOI: 10.1177/1010539513488795] [Citation(s) in RCA: 113] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The etiology of breast cancer might be explained by 2 mechanisms, namely, differentiation and proliferation of breast epithelial cells mediated by hormonal factors. We performed a systematic review and meta-analysis to update effects of risk factors for both mechanisms. MEDLINE and EMBASE were searched up to January 2011. Studies that assessed association between oral contraceptives (OC), hormonal replacement therapy (HRT), diabetes mellitus (DM), or breastfeeding and breast cancer were eligible. Relative risks with their confidence intervals (CIs) were extracted. A random-effects method was applied for pooling the effect size. The pooled odds ratios of OC, HRT, and DM were 1.10 (95% CI = 1.03-1.18), 1.23 (95% CI = 1.21-1.25), and 1.14 (95% CI = 1.09-1.19), respectively, whereas the pooled odds ratio of ever-breastfeeding was 0.72 (95% CI = 0.58-0.89). Our study suggests that OC, HRT, and DM might increase risks, whereas breastfeeding might lower risks of breast cancer.
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Mariani L, Gadducci A, Vizza E, Tomao S, Vici P. Vaginal atrophy in breast cancer survivors: role of vaginal estrogen therapy. Gynecol Endocrinol 2013; 29:25-9. [PMID: 22994445 DOI: 10.3109/09513590.2012.705389] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Early menopause and related vaginal atrophy is a well known side-effect of hormone adjuvant treatment in breast cancer patients, particularly during aromatase-inhibitors therapy. Due to estrogens contra-indication, proper therapy for such symptom remains often an inadequately addressed clinical problem. After an accurate assessment of the risk/benefit ratio, vaginal low-dose estrogen treatment (better with estriol) [corrected] may have a role in controlling vaginal atrophy in selected and informed breast cancer women.
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Affiliation(s)
- Luciano Mariani
- Department of Gynecologic Oncology, Regina Elena National Cancer Institute of Rome, Rome, Italy.
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Abstract
Cancer patients suffer from vaginal dryness and dyspareunia earlier and longer than the general population, with more severe and distressing symptoms. Life-style advices are the first step and vaginal lubricants can be tried, but they can't completely relieve atrophic symptoms. The most effective therapy is use of vaginal estrogens, but compliance and management are particularly difficult in estrogen sensitive cancer patients because of their systemic absorption. Compliance can be improved if they are begun at a very low dose and gradually increased until the lowest effective dose is reached. Promestriene only possesses an intramucosal effect, it can be used at very low doses in cancer patients suffering from urogenital symptoms.
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Affiliation(s)
- Lino Del Pup
- Gynecological Oncology, National Cancer Institute, Aviano, PN, Italy.
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Kamel M, Shouman S, El-Merzebany M, Kilic G, Veenstra T, Saeed M, Wagih M, Diaz-Arrastia C, Patel D, Salama S. Effect of tumour necrosis factor-alpha on estrogen metabolic pathways in breast cancer cells. J Cancer 2012; 3:310-21. [PMID: 22866165 PMCID: PMC3408695 DOI: 10.7150/jca.4584] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2012] [Accepted: 06/19/2012] [Indexed: 01/07/2023] Open
Abstract
Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been linked to breast cancer development. Estrogen metabolic pathway is also involved in breast carcinogenesis and DNA adducts formation. In this study we investigated the effect of TNF-α on the estrogen metabolic pathway in MCF-7, a breast cancer cell line. Capillary liquid chromatography/mass spectrometry (LC/MS) and High performance liquid chromatography (HPLC) were used for analysis of estrogen metabolites and estrogen-DNA adducts levels respectively. Reporter gene assay, Real time reverse transcription polymerase chain reaction (real time RT-PCR) and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes. TNF-α significantly increased the total EM and decreased the estrone (E1) / 17-β estradiol (E2) ratio. Moreover, it altered the expression of genes and enzymes involved in E2 activation and deactivation pathways e.g. Cytochrome P-450 1A1 (CYP1A1), Cytochrome P-450 1B1 (CYP1B1), Catechol-O-methyl transferase (COMT) and Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1 (NQO1). In addition, there were increased levels of some catechol estrogens e.g. 4-hydroxy-estrone (4-OHE1) and 2-hydroxyestradiol (2-OHE2) with decreased levels of methylated catechols e.g. 2-methoxy estradiol (2-MeOE2). DNA adducts especially 4-OHE1-[2]-1-N3 Adenine was significantly increased. TNF-α directs the estrogen metabolism into more hormonally active and carcinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.
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Affiliation(s)
- Marwa Kamel
- 1. Unit of Pharmacology, Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt
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Eriksson L, Czene K, Rosenberg L, Humphreys K, Hall P. The influence of mammographic density on breast tumor characteristics. Breast Cancer Res Treat 2012; 134:859-66. [DOI: 10.1007/s10549-012-2127-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Accepted: 06/04/2012] [Indexed: 11/29/2022]
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Vaginal pH-balanced gel for the control of atrophic vaginitis among breast cancer survivors: a randomized controlled trial. Obstet Gynecol 2012; 117:922-927. [PMID: 21422866 DOI: 10.1097/aog.0b013e3182118790] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To estimate the effects of vaginal pH-balanced gel on vaginal symptoms and atrophy in breast cancer survivors treated with chemotherapy or endocrine therapy. METHODS This was a randomized, double-blind, placebo-controlled study. Breast cancer survivors who experienced menopause after chemotherapy or endocrine therapy were voluntarily enrolled and randomly administered vaginal topical pH-balanced gel or placebo three times per week for 12 weeks. Vaginal dryness and dyspareunia were measured by visual analog scale, vaginal health index, and vaginal pH. The endometrium and ovary were evaluated by transvaginal ultrasonography. RESULTS Among 98 enrolled women, 86 completed the treatment (n=44 and n=42 for the pH-balanced gel group and placebo group, respectively). Vaginal dryness and dyspareunia improved more in the pH-balanced gel group than in the placebo group (baseline mean 8.20 compared with end-point mean 4.23 [P=.001] and 8.23 compared with 5.48 [P=.040], respectively). Vaginal pH-balanced gel reduced the vaginal pH (gel: baseline mean 6.49 compared with end-point mean 5.00; placebo: 6.22 compared with 5.69 [P<.001]), and enhanced vaginal maturation index (gel: 45.5 compared with 51.2; placebo: 46.4 compared with 47.9 [P<.001]) and vaginal health index (gel: 15.8 compared with 21.1; placebo 14.3 compared with 16.98 [P=.002]). There was no significant difference in adverse effects between the two groups except for mild irritation at the early time of pH-balanced gel administration. CONCLUSION Vaginal pH-balanced gel could relieve vaginal symptoms and improve vaginal health in breast cancer survivors who have experienced menopause after cancer treatment. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, www.clinicaltrials.gov, NCT00607295. LEVEL OF EVIDENCE I.
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Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry. Breast Cancer Res Treat 2012; 134:1209-20. [PMID: 22527103 DOI: 10.1007/s10549-012-2056-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2011] [Accepted: 04/01/2012] [Indexed: 01/06/2023]
Abstract
Epidemiologic studies of histologic types of breast cancer including mucinous, medullary, and tubular carcinomas have primarily relied on International Classification of Diseases-Oncology (ICD-O) codes assigned by local pathologists to define histology. Using data from the Breast Cancer Family Registry (BCFR), we compared histologic agreement between centralized BCFR pathology review and ICD-O codes available from local tumor registries among 3,260 breast cancer cases. Agreement was low to moderate for less common histologies; for example, only 55 and 26 % of cases classified as mucinous and medullary, respectively, by centralized review were similarly classified using ICD-O coding. We then evaluated risk factors for each histologic subtype by comparing each histologic case group defined by centralized review with a common set of 2,997 population-based controls using polytomous logistic regression. Parity [odds ratio (OR) = 0.4, 95 % confidence interval (95 % CI): 0.2-0.9, for parous vs. nulliparous], age at menarche (OR = 0.5, 95 % CI: 0.3-0.9, for age ≥13 vs. ≤11), and use of oral contraceptives (OCs) (OR = 0.5, 95 % CI: 0.2-0.8, OC use >5 years vs. never) were associated with mucinous carcinoma (N = 92 cases). Body mass index (BMI) (OR = 1.05, 95 % CI: 1.0-1.1, per unit of BMI) and high parity (OR = 2.6, 95 % CI: 1.1-6.0 for ≥3 live births vs. nulliparous) were associated with medullary carcinoma (N = 90 cases). We did not find any associations between breast cancer risk factors and tubular carcinoma (N = 86 cases). Relative risk estimates from analyses using ICD-O classifications of histology, rather than centralized review, resulted in attenuated, and/or more imprecise, associations. These findings suggest risk factor heterogeneity across breast cancer tumor histologies, and demonstrate the value of centralized pathology review for classifying rarer tumor types.
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Simon JA. Identifying and Treating Sexual Dysfunction in Postmenopausal Women: The Role of Estrogen. J Womens Health (Larchmt) 2011; 20:1453-65. [DOI: 10.1089/jwh.2010.2151] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Affiliation(s)
- James A. Simon
- George Washington University and Women's Health & Research Consultants, Washington, District of Columbia
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Haakensen VD, Bjøro T, Lüders T, Riis M, Bukholm IK, Kristensen VN, Troester MA, Homen MM, Ursin G, Børresen-Dale AL, Helland Å. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas. BMC Cancer 2011; 11:332. [PMID: 21812955 PMCID: PMC3163631 DOI: 10.1186/1471-2407-11-332] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2011] [Accepted: 08/03/2011] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. METHODS We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. RESULTS Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. CONCLUSIONS We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the local production of estradiol. This is the first report studying such associations in normal breast tissue in humans.
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Affiliation(s)
- Vilde D Haakensen
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
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Newcomb PA, Trentham-Dietz A, Hampton JM, Egan KM, Titus-Ernstoff L, Warren Andersen S, Greenberg ER, Willett WC. Late age at first full term birth is strongly associated with lobular breast cancer. Cancer 2011; 117:1946-56. [PMID: 21509772 PMCID: PMC3117094 DOI: 10.1002/cncr.25728] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2010] [Revised: 08/20/2010] [Accepted: 08/30/2010] [Indexed: 01/01/2023]
Abstract
BACKGROUND Late age at first full-term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades. METHODS The purpose of this population-based case-control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal-lobular breast cancer diagnosis in association with AFB and nulliparity. RESULTS AFB ≥30 years was associated with a 2.4-fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9-2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2-1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3-2.2) than for ductal (OR, 1.2; 95% CI, 1.1-1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer. CONCLUSIONS Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer.
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Affiliation(s)
- Polly A Newcomb
- University of Wisconsin Carbone Comprehensive Cancer Center, Madison, Wisconsin, USA.
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Use of Bioidentical Compounded Hormones for Menopausal Concerns: Cross-Sectional Survey in an Academic Menopause Center. J Womens Health (Larchmt) 2011; 20:559-65. [DOI: 10.1089/jwh.2009.1915] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Luo J, Margolis KL, Wactawski-Wende J, Horn K, Messina C, Stefanick ML, Tindle HA, Tong E, Rohan TE. Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study. BMJ 2011; 342:d1016. [PMID: 21363864 PMCID: PMC3047002 DOI: 10.1136/bmj.d1016] [Citation(s) in RCA: 141] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To examine the association between smoking and risk of invasive breast cancer using quantitative measures of lifetime passive and active smoking exposure among postmenopausal women. DESIGN Prospective cohort study. SETTING 40 clinical centres in the United States. PARTICIPANTS 79,990 women aged 50-79 enrolled in the Women's Health Initiative Observational Study during 1993-8. MAIN OUTCOME MEASURES Self reported active and passive smoking, pathologically confirmed invasive breast cancer. RESULTS In total, 3520 incident cases of invasive breast cancer were identified during an average of 10.3 years of follow-up. Compared with women who had never smoked, breast cancer risk was elevated by 9% among former smokers (hazard ratio 1.09 (95% CI 1.02 to 1.17)) and by 16% among current smokers (hazard ratio 1.16 (1.00 to 1.34)). Significantly higher breast cancer risk was observed in active smokers with high intensity and duration of smoking, as well as with initiation of smoking in the teenage years. The highest breast cancer risk was found among women who had smoked for ≥ 50 years or more (hazard ratio 1.35 (1.03 to 1.77) compared with all lifetime non-smokers, hazard ratio 1.45 (1.06 to 1.98) compared with lifetime non-smokers with no exposure to passive smoking). An increased risk of breast cancer persisted for up to 20 years after smoking cessation. Among women who had never smoked, after adjustment for potential confounders, those with the most extensive exposure to passive smoking (≥ 10 years' exposure in childhood, ≥ 20 years' exposure as an adult at home, and ≥ 10 years' exposure as an adult at work) had a 32% excess risk of breast cancer compared with those who had never been exposed to passive smoking (hazard ratio 1.32 (1.04 to 1.67)). However, there was no significant association in the other groups with lower exposure and no clear dose response to cumulative passive smoking exposure. CONCLUSIONS Active smoking was associated with an increase in breast cancer risk among postmenopausal women. There was also a suggestion of an association between passive smoking and increased risk of breast cancer.
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Affiliation(s)
- Juhua Luo
- Department of Community Medicine, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA
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Kotsopoulos J, Chen WY, Gates MA, Tworoger SS, Hankinson SE, Rosner BA. Risk factors for ductal and lobular breast cancer: results from the nurses' health study. Breast Cancer Res 2010; 12:R106. [PMID: 21143857 PMCID: PMC3046451 DOI: 10.1186/bcr2790] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2010] [Revised: 10/22/2010] [Accepted: 12/08/2010] [Indexed: 12/02/2022] Open
Abstract
Introduction Ductal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses' Health Study. Methods Multivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes. Results The associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het < 0.001) and postmenopausal hormone use (P-het < 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het ≥ 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors. Conclusions These data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology.
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Affiliation(s)
- Joanne Kotsopoulos
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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Abstract
Changes in ovarian hormone production may affect numerous health outcomes including vasomotor symptoms, cardiovascular disease (CVD), osteoporosis, cognition, depression, mood disorders, sexual function, and vaginal atrophy. We will compare age-related changes to those associated with reproductive aging and menopause and the effects of estrogen therapy on selected health outcomes. Hormone therapy (HT) reduces frequency and severity of hot flashes, prevents bone loss and osteoporotic fractures, and relieves vaginal atrophy. Nonhormone therapy trials with antidepressants or gabapentin for hot flash relief are promising. To date, clinical trial data are insufficient to recommend the use of HT for prevention or treatment of CVD, mood disorders, cognition, or sleep disorders. For some disease states, such as CVD and cognition, a "critical time window" has been proposed but not proven, such that estrogen use early in the menopause transition may be beneficial while estrogen use later in life would lead to increased health risks.
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Affiliation(s)
- JoAnn V Pinkerton
- Department of Obstetrics and Gynecology, Divisions of Midlife, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
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