1
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Rashid NS, Lamba N, Catalano PJ, Bi WL, Arnaout O, Tanguturi SK, Rahman R, Haas-Kogan DA, Lin NU, Wen PY, Aizer AA. Intracranial outcomes following neurosurgical resection in patients with brain metastases secondary to HER2-positive breast cancer versus other subtypes. Breast Cancer Res Treat 2025; 209:303-314. [PMID: 39367951 DOI: 10.1007/s10549-024-07493-6] [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: 07/16/2024] [Accepted: 09/06/2024] [Indexed: 10/07/2024]
Abstract
PURPOSE Neurosurgical resection serves an important role in select patients with breast cancer and brain metastases but can delay systemic therapy and yield complications. Consequently, identification of patients most likely to benefit from surgery is important. Given the poorer long-term intracranial responses to radiotherapy sometimes observed in HER2-positive (HER2 +) patients, we investigated whether neurosurgical resection is differentially beneficial in this population. METHODS We identified 633 patients with newly diagnosed brain metastases arising from breast cancer managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2010 and 2022. Patients were stratified by breast cancer subtype: HER2 + (N = 189), hormone receptor positive (HR +)/HER2- (N = 267), and triple negative (N = 177). Per-patient and per-metastasis outcomes were evaluated; interaction models assessing the impact of neurosurgical resection by subtype were constructed. RESULTS Relative to HR + /HER2- subtype, omission of upfront neurosurgical resection in patients with HER2 + disease was associated with increased subsequent utilization of salvage stereotactic radiation, whole brain radiotherapy, and craniotomy (interaction HR 2.02 [95% CI, 1.04-3.93], p = 0.04; HR 3.92 [95% CI, 1.24-12.40], p = 0.02; HR 4.98 [95% CI, 1.34-18.58], p = 0.02, respectively). Tumors stemming from HER2 + versus HR + /HER2- primaries displayed increased local recurrence when upfront neurosurgical resection was omitted (interaction HR 3.62 [95% CI, 1.06-12.38], p = 0.04). No such associations were noted when comparing triple negative to HR + /HER2- subtype (p-interaction > 0.05 in all cases). CONCLUSION Patients with HER2 + disease and brain metastases may disproportionately benefit from upfront neurosurgical resection relative to other subtypes. If validated, our results may suggest a lower threshold to consider surgery in brain metastases secondary to HER2 + breast cancer.
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Affiliation(s)
| | - Nayan Lamba
- Harvard Radiation Oncology Program, Harvard University, Boston, MA, USA
- Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, 75 Francis St, Boston, MA, 02115, USA
| | - Paul J Catalano
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Wenya Linda Bi
- Department of Neurosurgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Omar Arnaout
- Department of Neurosurgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Shyam K Tanguturi
- Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, 75 Francis St, Boston, MA, 02115, USA
| | - Rifaquat Rahman
- Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, 75 Francis St, Boston, MA, 02115, USA
| | - Daphne A Haas-Kogan
- Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, 75 Francis St, Boston, MA, 02115, USA
| | - Nancy U Lin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Patrick Y Wen
- Harvard Medical School, Boston, MA, USA
- Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Ayal A Aizer
- Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, 75 Francis St, Boston, MA, 02115, USA.
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Ren F, Ma Y, Zhang K, Luo Y, Pan R, Zhang J, Kan C, Hou N, Han F, Sun X. Exploring the multi-targeting phytoestrogen potential of Calycosin for cancer treatment: A review. Medicine (Baltimore) 2024; 103:e38023. [PMID: 38701310 PMCID: PMC11062656 DOI: 10.1097/md.0000000000038023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 04/05/2024] [Indexed: 05/05/2024] Open
Abstract
Cancer remains a significant challenge in the field of oncology, with the search for novel and effective treatments ongoing. Calycosin (CA), a phytoestrogen derived from traditional Chinese medicine, has garnered attention as a promising candidate. With its high targeting and low toxicity profile, CA has demonstrated medicinal potential across various diseases, including cancers, inflammation, and cardiovascular disease. Studies have revealed that CA possesses inhibitory effects against a diverse array of cancers. The underlying mechanism of action involves a reduction in tumor cell proliferation, induction of tumor cell apoptosis, and suppression of tumor cell migration and invasion. Furthermore, CA has been shown to enhance the efficacy of certain chemotherapeutic drugs, making it a potential component in treating malignant tumors. Given its high efficacy, low toxicity, and multi-targeting characteristics, CA holds considerable promise as a therapeutic agent for cancer treatment. The objective of this review is to present a synthesis of the current understanding of the antitumor mechanism of CA and its research progress.
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Affiliation(s)
- Fangbing Ren
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Yanhui Ma
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Kexin Zhang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Youhong Luo
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ruiyan Pan
- School of Pharmacy, Weifang Medical University, Weifang, China
| | - Jingwen Zhang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Chengxia Kan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ningning Hou
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Fang Han
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Xiaodong Sun
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
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Li F, Wang J, Yan YQ, Bai CZ, Guo JQ. CD147 promotes breast cancer migration and invasion by inducing epithelial-mesenchymal transition via the MAPK/ERK signaling pathway. BMC Cancer 2023; 23:1214. [PMID: 38066486 PMCID: PMC10709944 DOI: 10.1186/s12885-023-11724-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 12/06/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND CD147, a transmembrane glycoprotein, has been implicated in various cancer-related processes but its role in breast cancer remains poorly understood. Herein, we investigated the expression of CD147 in different breast cancer cell lines and explored its functional roles, including migration, invasion, drug resistance and modulation of key proteins associated with cancer progression. METHODS The expression of CD147 was assessed in MCF-10 A, BT549, MDA-MB-231 and MCF-7 breast cancer cell lines using qRT-PCR and Western blotting, following which lyposome transfections were performed, leading overexpression of CD147 in BT549 cells and knockdown of CD147 in MCF-7 cells. Scratch assays and Transwell invasion and were performed to evaluate the cells' migration and invasion abilities. Sensitivity to 5-FU was determined via CCK-8 assays, and the expression of Snail1, E-cadherin, Vimentin, MMP-9 and the MAPK/ERK pathway were analyzed by qRT-PCR and Western blotting. RESULTS Compared with normal beast epithelial cells, CD147 was highly expressed in all breast cancer cell lines, with the highest overexpression observed in MCF-7 cells and the lowest overexpression observed in BT549 cells. Overexpression of CD147 in BT549 cells increased, migration, invasion, viability and resistance to 5-FU of BT549 cells, while CD147 knockdown in MCF-7 cells reduced these properties of MCF-7 cells. Furthermore, CD147 influenced the expression of Snail1, Vimentin, E-cadherin, and MMP-9, suggesting its involvement in epithelial-mesenchymal transition (EMT) regulation. The MAPK/ERK pathway was activated by CD147 in BT549 cells, as indicated by increased p-MEK/MEK ratio and p-ERK/ERK ratio. In contrast, CD147 silencing in MCF-7 cells resulted in reduced p-MEK/MEK ratio and p-ERK/ERK ratio. CONCLUSION In summary, our findings suggest CD147 as a potential therapeutic target in breast cancer treatment, particularly in cases where drug resistance and metastasis are concerns, worthy of further explorations.
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Affiliation(s)
- Fang Li
- Department of Scientific Research, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, PR China.
| | - Jing Wang
- Department of Neurosurgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, PR China
| | - Yu-Qiong Yan
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, 030006, PR China
| | - Chong-Zhi Bai
- Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, 030012, PR China
| | - Ji-Qiang Guo
- Department of Clinical Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, PR China
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Sobhani N, Mondani G, Roviello G, Catalano M, Sirico M, D'Angelo A, Scaggiante B, Generali D. Cancer management during the COVID-19 world pandemic. Cancer Immunol Immunother 2023; 72:3427-3444. [PMID: 37642709 PMCID: PMC10992624 DOI: 10.1007/s00262-023-03524-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 08/10/2023] [Indexed: 08/31/2023]
Abstract
Since 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients; this has been caused by multiorgan failure, which might be due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors-functional receptors of SARS-CoV-2-in multiple organs. Patients with cancer may be particularly susceptible to COVID-19 because cancer treatments (e.g., chemotherapy, immunotherapy) suppress the immune system. Thus, patients with cancer and COVID-19 may have a poor prognosis. Knowing how to manage the treatment of patients with cancer who may be infected with SARS-CoV-2 is essential. Treatment decisions must be made on a case-by-case basis, and patient stratification is necessary during COVID-19 outbreaks. Here, we review the management of COVID-19 in patients with cancer and focus on the measures that should be adopted for these patients on the basis of the organs or tissues affected by cancer and by the tumor stage.
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Affiliation(s)
- Navid Sobhani
- Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX, 77030, USA.
| | - Giuseppina Mondani
- Royal Infirmary Hospital, Foresterhill Health Campus, Foresterhill Rd, Aberdeen, AB25 2ZN, UK
| | - Giandomenico Roviello
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy
| | - Martina Catalano
- Royal Infirmary Hospital, Foresterhill Health Campus, Foresterhill Rd, Aberdeen, AB25 2ZN, UK
| | - Marianna Sirico
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014, Meldola, Italy
| | - Alberto D'Angelo
- Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AX, UK
| | - Bruna Scaggiante
- Department of Life Sciences, University of Trieste, 34127, Trieste, Italy
| | - Daniele Generali
- Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127, Trieste, Italy
- Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, 26100, Cremona, Italy
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Loco-Regional Treatment of the Primary Tumor in De Novo Metastatic Breast Cancer Patients Undergoing Front-Line Chemotherapy. Cancers (Basel) 2022; 14:cancers14246237. [PMID: 36551722 PMCID: PMC9777012 DOI: 10.3390/cancers14246237] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/12/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Loco-regional therapy (LRT) in de novo metastatic breast cancer (MBC) has been investigated in several clinical trials, with heterogeneous and conflicting results. METHODS We conducted a retrospective study of de novo MBC patients treated with front-line chemotherapy (FLC) followed by LRT of the primary tumor. Our aims were to evaluate the characteristics, treatment, and oncological outcomes in terms of progression-free survival (PFS), distant progression-free survival (DPFS), and overall survival (OS) of de novo MBC. We also investigated possible subgroups of patients with better outcomes according to menopausal status, biological sub-type, location, number of metastases, and radiologic complete response after FLC. RESULTS We included 61 patients in the study. After a median follow-up of 55 months, disease progression occurred in 60.7% of patients and 49.2% died. There were no significant differences in PFS, DPFS, and OS between different subgroups of de novo MBC patients. A trend toward better PFS and DPFS was observed in triple-positive tumors, without a statistically significant difference in OS. CONCLUSIONS No specific subgroup of de novo MBC patients showed a statistically significant survival advantage after FLC followed by LRT of the primary tumor.
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Stavrovski T, Pereira P. Role of interventional oncology for treatment of liver metastases: evidence based best practice. Br J Radiol 2022; 95:20211376. [PMID: 35976260 PMCID: PMC9815747 DOI: 10.1259/bjr.20211376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 07/17/2022] [Accepted: 07/28/2022] [Indexed: 01/13/2023] Open
Abstract
The presence of liver metastases is associated with a poor prognosis in many cancer diseases. Multiple studies during the last decades aimed to find out the best multimodal therapy to achieve an ideal, safe and highly effective treatment. In addition to established therapies such as systemic therapy, surgery and radiation therapy, interventional oncology with thermal ablation, transarterial chemoembolisation and radioembolisation, is becoming the fourth pillar of cancer therapies and is part of a personalised treatments' strategy. This review informs about the most popular currently performed interventional oncological treatments in patients with liver metastases.
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Affiliation(s)
- Tomislav Stavrovski
- Zentrum für Radiologie, Minimal-Invasive Therapien und Nuklearmedizin, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunnen, Heilbronn, Germany
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-Invasive Therapien und Nuklearmedizin, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunnen, Heilbronn, Germany
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7
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Foo SL, Sachaphibulkij K, Lee CLY, Yap GLR, Cui J, Arumugam T, Lim LHK. Breast cancer metastasis to brain results in recruitment and activation of microglia through annexin-A1/formyl peptide receptor signaling. Breast Cancer Res 2022; 24:25. [PMID: 35382852 PMCID: PMC8985313 DOI: 10.1186/s13058-022-01514-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 02/25/2022] [Indexed: 12/26/2022] Open
Abstract
Background Despite advancements in therapies, brain metastasis in patients with triple negative subtype of breast cancer remains a therapeutic challenge. Activated microglia are often observed in close proximity to, or within, malignant tumor masses, suggesting a critical role that microglia play in brain tumor progression. Annexin-A1 (ANXA1), a glucocorticoid-regulated protein with immune-regulatory properties, has been implicated in the growth and metastasis of many cancers. Its role in breast cancer-microglia signaling crosstalk is not known. Methods The importance of microglia proliferation and activation in breast cancer to brain metastasis was evaluated in MMTV-Wnt1 spontaneous mammary tumor mice and BALBc mice injected with 4T1 murine breast cancer cells into the carotid artery using flow cytometry. 4T1 induced-proliferation and migration of primary microglia and BV2 microglia cells were evaluated using 2D and coculture transwell assays. The requirement of ANXA1 in these functions was examined using a Crispr/Cas9 deletion mutant of ANXA1 in 4T1 breast cancer cells as well as BV2 microglia. Small molecule inhibition of the ANXA1 receptor FPR1 and FPR2 were also examined. The signaling pathways involved in these interactions were assessed using western blotting. The association between lymph node positive recurrence-free patient survival and distant metastasis-free patient survival and ANXA1 and FPR1 and FPR2 expression was examined using TCGA datasets. Results Microglia activation is observed prior to brain metastasis in MMTV-Wnt1 mice with primary and secondary metastasis in the periphery. Metastatic 4T1 mammary cancer cells secrete ANXA1 to promote microglial migration, which in turn, enhances tumor cell migration. Silencing of ANXA1 in 4T1 cells by Crispr/Cas9 deletion, or using inhibitors of FPR1 or FPR2 inhibits microglia migration and leads to reduced activation of STAT3. Finally, elevated ANXA1, FPR1 and FPR2 is significantly associated with poor outcome in lymph node positive patients, particularly, for distant metastasis free patient survival. Conclusions The present study uncovered a network encompassing autocrine/paracrine ANXA1 signaling between metastatic mammary cancer cells and microglia that drives microglial recruitment and activation. Inhibition of ANXA1 and/or its receptor may be therapeutically rewarding in the treatment of breast cancer and secondary metastasis to the brain. Supplementary Information The online version contains supplementary material available at 10.1186/s13058-022-01514-2.
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Abbaspour M, Akbari V. Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence. Expert Rev Vaccines 2021; 21:337-353. [PMID: 34932427 DOI: 10.1080/14760584.2022.2021884] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Breast cancer (BC) is the first common neoplastic malignancy and the second leading cause of death in women worldwide. Conventional treatments for BC are often associated with severe side effects and may even lead to late recurrence. For this reason, in recent years, cancer immunotherapy (e.g., cancer vaccines), a novel approach based on the specificity and amplification of acquired immune responses, has been considered as a potential candidate in particular to treat metastatic BC. AREAS COVERED In this review, we summarize and discuss the recent development of therapeutic vaccines for BC, use of specific BC cellular antigens, antigen selection, and probable causes for their insufficient effectiveness. EXPERT OPINION Despite development of several different BC vaccines strategies including protein/peptide, dendritic cell, and genetic vaccines, until now, no BC vaccine has been approved for clinical use. Most of the current BC vaccines themselves fail to bring clinical benefit to BC patients and are applied in combination with radiotherapy, chemotherapy, or targeted therapy. It is hoped that with advances in our knowledge about tumor microenvironment and the development of novel combination strategies, the tumor immunosuppressive mechanisms can be overcome and prolonged immunologic and effective anti-tumor response can be developed in patients.
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Affiliation(s)
- Maryam Abbaspour
- Department of pharmaceutical biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Vajihe Akbari
- Department of pharmaceutical biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.,Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Li K, Zhou C, Yu Y, Niu L, Zhang W, Wang B, He J, Ge G. Metastatic Pattern Discriminates Survival Benefit of Type of Surgery in Patients With De Novo Stage IV Breast Cancer Based on SEER Database. Front Surg 2021; 8:696628. [PMID: 34805256 PMCID: PMC8595123 DOI: 10.3389/fsurg.2021.696628] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 09/16/2021] [Indexed: 12/22/2022] Open
Abstract
Background: The role of surgery and surgery type in de novo stage IV breast cancer (BC) is unclear. Methods: We carried out a retrospective cohort study that included the data of 4,108 individuals with de novo stage IV BC abstracted from SEER (Surveillance, Epidemiology, and End Results) data resource from 2010 to 2015. The patients were stratified into the non-surgery group, breast-conserving (BCS) surgery group, and mastectomy group. Inverse probability propensity score weighting (IPTW) was then used to balance clinicopathologic factors. Overall survival (OS), as well as the breast cancer-specific survival (BCSS), was assessed in the three groups using Kaplan–Meier analysis and COX model. Subgroups were stratified by metastatic sites for analysis. Results: Of the 4,108 patients, 48.5% received surgery and were stratified into the BCS group (574 cases) and mastectomy group (1,419 cases). After IPTW balance demographic and clinicopathologic factors, BCS and mastectomy groups had better OS (BCS group: HR, 0.61; 95% CI: 0.49–0.75; mastectomy group: HR, 0.7; 95% CI: 0.63–0.79) and BCSS (BCS group: HR, 0.6; 95% CI, 0.47–0.75; mastectomy group: HR, 0.71; 95% CI, 0.63–0.81) than the non-therapy group. Subgroup analyses revealed that BCS, rather than mastectomy, was linked to better OS (HR, 0.66; 95% CI: 0.48–0.91) and BCSS (HR, 0.63; 95% CI: 0.45–0.89) for patients with bone-only metastasis. For patients with viscera metastasis or bone+viscera metastases, BCS achieved similar OS (viscera metastasis: HR, 1.05; 95% CI: 0.74–1.48; bone+viscera metastases: HR, 1.01; 95% CI: 0.64–1.61) and BCSS (viscera metastasis: HR, 0.94; 95% CI: 0.64–1.38; bone+viscera metastases: HR, 1.06; 95% CI: 0.66–1.73) in contrast with mastectomy. Conclusions: Local surgery for patients with distant metastasis (DS) exhibited a remarkable survival advantage in contrast with non-operative management. BCS may have more survival benefits for patients with de novo stage IV BC with bone-only metastasis than other metastatic sites. Decisions on de novo stage IV BC primary surgery should be tailored to the metastatic pattern.
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Affiliation(s)
- Kunlong Li
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.,School of Medicine, Xi'an Jiaotong University, Xi'an, China
| | - Can Zhou
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yan Yu
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Ligang Niu
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Wei Zhang
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Bin Wang
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Jianjun He
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Guanqun Ge
- Department of Breast Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
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10
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Rinnerthaler G, Gampenrieder SP, Petzer A, Hubalek M, Petru E, Sandholzer M, Andel J, Balic M, Melchardt T, Hauser-Kronberger C, Schmitt CA, Ulmer H, Greil R. Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: results of a phase II trial (AGMT MBC-6). Ther Adv Med Oncol 2021; 13:17588359211042301. [PMID: 34691243 PMCID: PMC8529308 DOI: 10.1177/17588359211042301] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 08/09/2021] [Indexed: 11/15/2022] Open
Abstract
Background: Bendamustine, a medication approved for the treatment of indolent non-Hodgkin
lymphoma, has already shown anticancer activity in metastatic breast cancer
(MBC). Here, we present the results of a phase II trial of bendamustine in
combination with capecitabine in pre-treated patients with MBC. Patients and methods: AGMT MBC-6 is a multicentre, open-label, single-arm phase II study in
HER2-negative MBC. All patients were pre-treated with anthracyclines and/or
taxans and had measurable disease. Patients received per os
1000 mg/m2 capecitabine twice daily on days 1 to 14 in
combination with 80 mg/m2 bendamustine intravenously on days 1
and 8 of a 3-week cycle for a maximum of eight cycles, followed by a
capecitabine maintenance therapy. The primary endpoint was overall response
rate (ORR). Results: From September 2013 to May 2015, 40 patients were recruited in eight Austrian
centres. The median age was 60 years (range 29–77). Twenty-five per cent of
patients had triple-negative breast cancer (TNBC) and 93% showed visceral
involvement. With 17 partial and one complete remission, ORR was 46%. Median
progression-free survival (PFS) was 7.5 months [95% confidence interval (CI)
6.1–10.7]. The most common non-haematological adverse events (AEs) of grade
3 were hand-foot syndrome (13%), fatigue (10%), nausea (8%), and dyspnoea
(8%). One grade 4 non-haematological AE (hepatic failure) and three grade 4
haematological AEs (neutropenia) were observed. One patient died of
restrictive cardiomyopathy, in which a relationship to capecitabine cannot
be excluded, but seems unlikely. Conclusion: The combination of capecitabine and bendamustine shows promising efficacy and
moderate toxicity. Further evaluation of this drug combination is
warranted. The clinical trial AGMT MBC-6 was registered at ClinicalTrials.gov,
(https://clinicaltrials.gov/; identifier: NCT01891227).
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Affiliation(s)
- Gabriel Rinnerthaler
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Simon Peter Gampenrieder
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Andreas Petzer
- Internal Department I for Medical Oncology and Hematology, Barmherzige Schwestern Hospital/Linz, Linz, Austria
| | - Michael Hubalek
- Department of Obstetrics and Gynaecology, Innsbruck Medical University, Innsbruck, Austria
| | - Edgar Petru
- Department of Obstetrics and Gynaecology, Medical University Graz, Graz, Austria
| | - Margit Sandholzer
- Department of Oncology, Hematology and Gastroenterology, Infectiology, Academic Teaching Hospital Feldkirch, Austria
| | - Johannes Andel
- Department of Internal Medicine II, Pyhrn-Eisenwurzen Klinikum Steyr, Steyr, Austria
| | - Marija Balic
- Division of Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
| | - Thomas Melchardt
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, AustriaSalzburg Cancer Research Institute with Laboratory of Immunological and Molecular Cancer Research and Center for Clinical Cancer and Immunology Trials, Salzburg, Austria
| | | | - Clemens A Schmitt
- Department of Internal Medicine 3 - Hematology and Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria
| | - Hanno Ulmer
- Department of Medical Statistics and Informatics, Medical University Innsbruck, Innsbruck, Austria
| | - Richard Greil
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria
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11
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Bhattacharyya O, Li Y, Fisher JL, Tsung A, Eskander MF, Hamad A, Obeng-Gyasi S. Low neighborhood socioeconomic status is associated with higher mortality and increased surgery utilization among metastatic breast cancer patients. Breast 2021; 59:314-320. [PMID: 34388697 PMCID: PMC8361177 DOI: 10.1016/j.breast.2021.08.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/31/2021] [Accepted: 08/02/2021] [Indexed: 12/16/2022] Open
Abstract
PURPOSE Low socioeconomic status (SES) is associated with advanced stage, lower-quality care, and higher mortality among breast cancer patients. The purpose of this study is to examine the association between neighborhood SES (nSES), surgical management, and disease-specific mortality in de novo metastatic breast cancer (MBC) patients in the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS MBC patients ages 18 to 85+ years diagnosed from 2010 through 2016 were identified in SEER. The cohort was divided into low, middle, and high nSES based on the NCI census tract-level index. Univariable and multivariable analyses were used to examine the relationship between nSES, surgery, and disease specific mortality in MBC patients. RESULTS There were 24,532 de novo MBC patients who met study criteria, with 28.7 % undergoing surgery. Over the study period, surgery utilization decreased across all nSES groups. However, lower nSES was associated with a higher odds of undergoing surgery (low OR 1.25 [1.15-1.36] p < 0.001; middle OR 1.09 [1.01-1.18] p = 0.022; ref high). Living in an area with lower SES was associated with a worse disease specific mortality (low HR 1.24 [1.25, 1.44; ], middle 1.20 [1.1-1.29]: ref high). Specifically, there was a 9.26 month mean survival differences between the lowest (41.02 ± 0.47 months) and highest (50.28 ± 0.47 months) nSES groups. CONCLUSION These results suggest area of residence may contribute to differences in surgical management and clinical outcomes among de novo MBC patients. Future studies should examine the contributions of patient characteristics and preferences within the context of surgeon recommendations.
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Affiliation(s)
| | - Yaming Li
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH, USA
| | - James L Fisher
- The Ohio State University College of Medicine, Columbus, OH, USA; James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH, USA
| | - Mariam F Eskander
- Indiana University Purdue University, Department of Economics, Indianapolis, IN, USA
| | - Ahmad Hamad
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH, USA
| | - Samilia Obeng-Gyasi
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH, USA.
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12
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Zhang Z, Lin M, Wang J, Yang F, Yang P, Liu Y, Chen Z, Zheng Y. Calycosin inhibits breast cancer cell migration and invasion by suppressing EMT via BATF/TGF-β1. Aging (Albany NY) 2021; 13:16009-16023. [PMID: 34096887 PMCID: PMC8266341 DOI: 10.18632/aging.203093] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 04/29/2021] [Indexed: 12/16/2022]
Abstract
In this study, we investigated the effects of calycosin on breast cancer cell progression and their underlying mechanisms. Calycosin dose- and time-dependently inhibited proliferation, migration, and invasion by T47D and MCF-7 breast cancer cells by downregulating basic leucine zipper ATF-like transcription factor (BATF) expression. Moreover, BATF promoted breast cancer cell migration and invasiveness by increasing TGFβ1 mRNA and protein levels. Bioinformatics analysis, dual luciferase reporter assays, and chromatin immunoprecipitation assays confirmed the presence of BATF-binding sites in the promoter sequence of TGFβ1 gene. Calycosin treatment inhibited epithelial-mesenchymal transition (EMT) of breast cancer cells by significantly increasing E-cadherin levels and decreasing N-cadherin, Vimentin, CD147, MMP-2, and MMP-9 levels through downregulation of BATF and TGFβ1. TGFβ1 knockdown reduced the migration and invasiveness of BATF-overexpressing breast cancer cells, whereas incubation with TGFβ1 enhanced the migration and invasiveness of calycosin-treated breast cancer cells. Our findings demonstrated that calycosin inhibited EMT and progression of breast cancer cells by suppressing BATF/TGFβ1 signaling. This suggests calycosin would be a promising therapeutic option for breast cancer patients.
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Affiliation(s)
- Zhenxia Zhang
- School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, Guangdong, China
| | - Min Lin
- School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, Guangdong, China
| | - Junli Wang
- Center of Reproductive Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China
| | - Fenglian Yang
- School of Pharmacy, Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China
| | - Peikui Yang
- School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, Guangdong, China
| | - Yaqun Liu
- School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, Guangdong, China
| | - Zikai Chen
- School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, Guangdong, China
| | - Yuzhong Zheng
- School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, Guangdong, China
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13
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Liao H, Huang W, Liu Y, Pei W, Li H. Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis. Front Oncol 2021; 11:608781. [PMID: 34012912 PMCID: PMC8127838 DOI: 10.3389/fonc.2021.608781] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 04/06/2021] [Indexed: 12/24/2022] Open
Abstract
Purpose To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients. Methods A comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens. Results Twelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70–0.86), Lap-Cap (0.64, 0.59–0.69), Tra-Cap (0.63, 0.56–0.70), Cap (0.50, 0.45–0.56), Ner (0.59, 0.51–0.69), Per-Tra-Cap (0.68, 0.59–0.79), and Ner-Cap (0.72, 0.64–0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52–0.99), Cap (0.68, 0.49–0.96), and Ner (0.65, 0.45–0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22–56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%). Conclusions These results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.
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Affiliation(s)
- Hao Liao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Wenfa Huang
- Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen, China
| | - Yaxin Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Wendi Pei
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing, China
| | - Huiping Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China
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14
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Yuan C, Chang K, Xu C, Li Q, Du Z. High expression of DLL3 is associated with a poor prognosis and immune infiltration in invasive breast cancer patients. Transl Oncol 2021; 14:101080. [PMID: 33915517 PMCID: PMC8093948 DOI: 10.1016/j.tranon.2021.101080] [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: 12/03/2020] [Revised: 03/08/2021] [Accepted: 03/17/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Previous studies have shown the prognostic value of delta like canonical Notch ligand 3 (DLL3) in patients with different types of tumors, but the role and predictive value of DLL3 in invasive breast cancer (IBC) have not been reported. In this study, we explored the prognostic ability and potential ways of DLL3 in IBC patients. METHODS We retrospectively enrolled 130 IBC patients from a single institution from 2004 to 2019 for bioinformatics and statistical analysis. The Cancer Genome Atlas breast invasive carcinoma (TCGA-BRCA) cohort was used for verification. RESULTS High expression of DLL3 was associated with overall survival (OS) in IBC patients (P = 0.023). Multivariate analysis further showed that DLL3 expression was an independent prognostic factor (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.01-1.15; P = 0.017). Time-dependent receiver operating characteristic (ROC) with the area under the curve (0.786) demonstrated that DLL3 expression can predict the survival outcome of IBC patients. Furthermore, the expression of DLL3 was related to a variety of tumor infiltrating immune cells (TIICs), particularly T cells regulatory (Tregs). Gene set enrichment analysis (GSEA) and immunohistochemistry (IHC) results indicated that DLL3 was closely related to p53 signaling pathway. CONCLUSIONS High expression of DLL3 was associated with poor prognosis and immune cell infiltration in IBC patients. Moreover, P53 signaling pathway may be the key pathway.
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Affiliation(s)
- Chong Yuan
- Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Kaili Chang
- Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Chenyue Xu
- Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Qingquan Li
- Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
| | - Zunguo Du
- Department of pathology, Huashan hospital, Fudan university, No.12 Middle Urumqi road, Shanghai 200032, China.
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15
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Lai H, Jiang W, Zhao J, Dinglin X, Li Y, Li S, Wang Y, Yao H. Global Trend in Research and Development of CDK4/6 Inhibitors for Clinical Cancer Therapy: A Bibliometric Analysis. J Cancer 2021; 12:3539-3547. [PMID: 33995631 PMCID: PMC8120189 DOI: 10.7150/jca.51609] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 03/25/2021] [Indexed: 02/03/2023] Open
Abstract
Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are frequently used anti-cancer agents in hormone receptor-positive breast cancers. This study assessed the course of research and development (R&D) for CDK4/6 inhibitors in terms of publications over the past two decades. Methods: The Web of Science (WOS) and PubMed databases were searched to identify publications related to research on CDK4/6 inhibitors since 2001. The VOS Viewer software was used to analyze co-occurring keywords to stratify the publication data and collaborations in research. Results: There were 1395 publications related to research on CDK4/6 inhibitors since 2001. Eight of the top 10 institutions originated from the USA and the other two were a Swiss Pharmaceutical Company and French Research Institute. Bardia A, the first author for some of the articles published in the USA, was the most prolific with 25 publications. The journal with the most publications was Cancer Res with 162 publications. Basic research comprised six of the 10 most frequently cited publications and the rest consisted of three reviews and a clinical trial. The most common keywords for publications since 2011 were “palbociclib”, “abemaciclib”, “ribociclib” and “double blind”, indicating the successful development of CDK4/6 inhibitors as anticancer drugs. Conclusions: This study provides a comprehensive review of the CDK4/6 inhibitors R&D history. The data imply that drug development in this field is a decade-long process and clinical trials have been performed before clinical applications. Thereafter, research was conducted on the adverse effects and drug resistance associated with the inhibitors.
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Affiliation(s)
- Hongna Lai
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou 510120, China.,Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Wei Jiang
- Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Jianli Zhao
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou 510120, China.,Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Xiaoxiao Dinglin
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou 510120, China.,Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Yudong Li
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou 510120, China.,Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Shunying Li
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou 510120, China.,Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Ying Wang
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou 510120, China.,Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Herui Yao
- Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou 510120, China.,Breast Tumour Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
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16
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Nagao A, Noie T, Horiuch H, Yamada H, Momiyama M, Nakajima K, Satou S, Satodate H, Nara S, Harihara Y. Long-term survival after pancreatic metastasis resection from breast cancer: a systematic literature review. Surg Case Rep 2021; 7:39. [PMID: 33534098 PMCID: PMC7859131 DOI: 10.1186/s40792-021-01124-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 01/27/2021] [Indexed: 12/31/2022] Open
Abstract
Background Patients with advanced-stage breast cancer often demonstrate pancreatic metastases. However, pancreatic metastases resection from breast cancer has been rarely performed, with only 20 cases having been reported to date. Case presentation A 49-year-old woman presented to our hospital in September 2003 with complaints of uncontrollable oozing from her left breast tumor. Computed tomography revealed a left breast tumor approximately 9.3 cm in diameter as well as heterogeneously enhanced solid mass lesions with necrotic foci in the pancreatic tail and body, up to 6.2 cm, which were radiologically diagnosed as pancreatic metastases from breast cancer. An emergent left simple mastectomy was performed to control bleeding. After epirubicin and cyclophosphamide hydrate treatment failed to improve her condition, the pancreatic metastases responded to weekly paclitaxel treatment, but eventually regrew. The patient underwent distal pancreatectomy with splenectomy, left adrenalectomy, partial stomach resection, and paraaortic lymph nodes excision in December 2004 after no other metastasis was confirmed. Furthermore, she received radiation therapy for left parasternal lymph node metastasis 6 months later. The patient recovered well. Consequently, she has no evidence of disease > 15 years after pancreatectomy. Conclusions This is the first reported case of pancreatectomy for pancreatic metastases from breast cancer, which was simultaneously diagnosed. Patients with no metastasis other than resectable pancreatic metastases and breast cancer and who possess some sensitivity for chemotherapy may benefit from pancreatectomy.
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Affiliation(s)
- Atsuki Nagao
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Tamaki Noie
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.
| | - Hajime Horiuch
- Department of Pathology, NTT Medical Center Tokyo, Tokyo, Japan
| | - Haruyasu Yamada
- Department of Radiology, NTT Medical Center Tokyo, Tokyo, Japan
| | - Masashi Momiyama
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Kentaro Nakajima
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Shouichi Satou
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Hitoshi Satodate
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Satoshi Nara
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Yasushi Harihara
- Department of Surgery, NTT Medical Center Tokyo, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
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17
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Roze J, Sendino Garví E, Stelloo E, Stangl C, Sereno F, Duran K, Groeneweg J, Paijens S, Nijman H, van Meurs H, van Lonkhuijzen L, Piek J, Lok C, Jonges G, Witteveen P, Verheijen R, van Haaften G, Zweemer R, Monroe G. In Vitro Systematic Drug Testing Reveals Carboplatin, Paclitaxel, and Alpelisib as a Potential Novel Combination Treatment for Adult Granulosa Cell Tumors. Cancers (Basel) 2021; 13:368. [PMID: 33498451 PMCID: PMC7864192 DOI: 10.3390/cancers13030368] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/15/2021] [Accepted: 01/18/2021] [Indexed: 12/11/2022] Open
Abstract
Adult granulosa cell tumors (AGCTs) arise from the estrogen-producing granulosa cells. Treatment of recurrence remains a clinical challenge, as systemic anti-hormonal treatment or chemotherapy is only effective in selected patients. We established a method to rapidly screen for drug responses in vitro using direct patient-derived cell lines in order to optimize treatment selection. The response to 11 monotherapies and 12 combination therapies, including chemotherapeutic, anti-hormonal, and targeted agents, were tested in 12 AGCT-patient-derived cell lines and an AGCT cell line (KGN). Drug screens were performed within 3 weeks after tissue collection by measurement of cell viability 72 h after drug application. The potential synergy of drug combinations was assessed. The human maximum drug plasma concentration (Cmax) and steady state (Css) thresholds obtained from available phase I/II clinical trials were used to predict potential toxicity in patients. Patient-derived AGCT cell lines demonstrated resistance to all monotherapies. All cell lines showed synergistic growth inhibition by combination treatment with carboplatin, paclitaxel, and alpelisib at a concentration needed to obtain 50% cell death (IC50) that are below the maximum achievable concentration in patients (IC50 < Cmax). We show that AGCT cell lines can be rapidly established and used for patient-specific in vitro drug testing, which may guide treatment decisions. Combination treatment with carboplatin, paclitaxel, and alpelisib was consistently effective in AGCT cell lines and should be further studied as a potential effective combination for AGCT treatment in patients.
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Affiliation(s)
- Joline Roze
- Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands; (J.R.); (J.G.); (R.V.); (G.M.)
| | - Elena Sendino Garví
- Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Oncode Institute, Utrecht University, 3584 CX Utrecht, The Netherlands; (E.S.G.); (E.S.); (C.S.); (F.S.); (K.D.); (G.v.H.)
| | - Ellen Stelloo
- Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Oncode Institute, Utrecht University, 3584 CX Utrecht, The Netherlands; (E.S.G.); (E.S.); (C.S.); (F.S.); (K.D.); (G.v.H.)
| | - Christina Stangl
- Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Oncode Institute, Utrecht University, 3584 CX Utrecht, The Netherlands; (E.S.G.); (E.S.); (C.S.); (F.S.); (K.D.); (G.v.H.)
| | - Ferdinando Sereno
- Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Oncode Institute, Utrecht University, 3584 CX Utrecht, The Netherlands; (E.S.G.); (E.S.); (C.S.); (F.S.); (K.D.); (G.v.H.)
| | - Karen Duran
- Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Oncode Institute, Utrecht University, 3584 CX Utrecht, The Netherlands; (E.S.G.); (E.S.); (C.S.); (F.S.); (K.D.); (G.v.H.)
| | - Jolijn Groeneweg
- Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands; (J.R.); (J.G.); (R.V.); (G.M.)
| | - Sterre Paijens
- Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (S.P.); (H.N.)
| | - Hans Nijman
- Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (S.P.); (H.N.)
| | - Hannah van Meurs
- Department of Gynecological Oncology, Centre for Gynaecological Oncology Amsterdam, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands; (H.v.M.); (L.v.L.)
| | - Luc van Lonkhuijzen
- Department of Gynecological Oncology, Centre for Gynaecological Oncology Amsterdam, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands; (H.v.M.); (L.v.L.)
| | - Jurgen Piek
- Department of Obstetrics and Gynaecology, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands;
| | - Christianne Lok
- Department of Gynaecological Oncology, Centre for Gynaecological Oncology Amsterdam, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands;
| | - Geertruida Jonges
- Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands;
| | - Petronella Witteveen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands;
| | - René Verheijen
- Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands; (J.R.); (J.G.); (R.V.); (G.M.)
| | - Gijs van Haaften
- Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Oncode Institute, Utrecht University, 3584 CX Utrecht, The Netherlands; (E.S.G.); (E.S.); (C.S.); (F.S.); (K.D.); (G.v.H.)
| | - Ronald Zweemer
- Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands; (J.R.); (J.G.); (R.V.); (G.M.)
| | - Glen Monroe
- Department of Gynaecological Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands; (J.R.); (J.G.); (R.V.); (G.M.)
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18
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Low Expression of miR-20a-5p Predicts Benefit to Bevacizumab in Metastatic Breast Cancer Patients Treated within the TANIA Phase III Trial. J Clin Med 2020; 9:jcm9061663. [PMID: 32492882 PMCID: PMC7355487 DOI: 10.3390/jcm9061663] [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] [Received: 04/26/2020] [Revised: 05/22/2020] [Accepted: 05/25/2020] [Indexed: 02/07/2023] Open
Abstract
Background: In metastatic breast cancer (MBC) patients, no biomarker predicting benefit to a bevacizumab-containing therapy has been established yet. MicroRNAs (miRNAs) are involved in angiogenesis and treatment resistance and therefore could be of predictive value. Methods: Profiling of 754 miRNAs was performed in tumor samples of 58 MBC patients treated with a bevacizumab-containing first-line regimen (learning set). Based on progression-free survival (PFS), patients were divided into responders (R) and non-responders (NR). Differentially expressed miRNAs between R and NR were analyzed in a cohort of 57 patients treated with first-line chemotherapy without bevacizumab (control set), to exclude miRNAs providing prognostic information. MiRNA candidates significantly associated with PFS in multivariate analysis were further validated in tumor samples of 203 patients treated within the phase III trial TANIA randomizing between chemotherapy either alone or with bevacizumab after progression on first-line bevacizumab. Results: Low expression of miR-20a-5p (multivariate p = 0.035) and miR-21-5p (multivariate p = 0.004) were significantly associated with longer PFS in the learning set, but not in the control set. In samples from the TANIA trial, low expression of miR-20a-5p was also significantly associated with longer PFS (hazard ration (HR) 0.60; 95%-CI 0.37–0.89; p = 0.012) and longer overall survival (OS; HR 0.54; 95%-CI 0.32–0.83; p = 0.007) in the bevacizumab arm but not in the chemotherapy-only arm (PFS: HR 0.73, p = 0.119; OS: HR 1.01; p = 0.964). For miR-21-5p no significant association with PFS or OS in both treatment arms was observed. Conclusion: MiR-20a-5p expression in breast cancer tissue was predictive for a greater benefit from bevacizumab-containing therapy in two independent cohorts.
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Lin Y, Huang K, Zeng Q, Zhang J, Song C. Impact of breast surgery on survival of patients with stage IV breast cancer: a SEER population-based propensity score matching analysis. PeerJ 2020; 8:e8694. [PMID: 32219021 PMCID: PMC7085290 DOI: 10.7717/peerj.8694] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 02/05/2020] [Indexed: 12/14/2022] Open
Abstract
Background Breast surgery for stage IV breast cancer remains controversial. The aim of this study was to investigate the impact of breast surgery on survival of stage IV breast cancer patients based on the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Methods In total, 13,034 patients were selected and divided into surgery and non-surgery groups. Univariate and multivariable analyses were conducted to determine factors related to survival. Propensity score matching method was utilized to achieve balanced covariates across different groups. One-to-one (1:1) PSM was conducted to construct a matched sample consisting of pairs of surgery and non-surgery subjects. Breast cancer-specific survival (BCSS) and overall survival (OS) of the two groups were assessed by Kaplan-Meier plots and Cox proportional hazard regression models. Stratified analysis according to different variables was also performed. Results Patients treated with breast surgery were more likely to be younger, smaller tumor size, more advanced nodal status, higher histology grade and higher proportion of bone-only metastasis. Those who received chemotherapy and radiotherapy also tended to be treated with surgery. After adjustment for potential confounders, breast surgery group exhibited a better survival both in BCSS (HR = 0.557, 95% CI [0.523-0.594], p < 0.001) and OS (HR = 0.571, 95% CI [0.537-0.607], p < 0.001). After propensity score matching, the surgery and non-surgery group consisted of 2,269 patients respectively. The median survival time was 43 months for the surgery group and 27 months for the non-surgery group. Kaplan-Meier curves indicated that breast surgery could clearly improve both the BCSS and OS for patients with stage IV breast cancer. On multivariate analysis, surgery group was associated with a better survival compared with the non-surgery group (BCSS: HR = 0.542, 95% CI [0.499-0.589], p < 0.001; OS: HR = 0.555, 95% CI [0.512-0.601], p < 0.001). Furthermore, this survival advantage persisted in all subgroups irrespective of age, race, tumor size, nodal status, histology grade, molecular subtype, chemotherapy status, radiotherapy status or status of distant metastasis. Conclusion Our study provided additional evidence that patients with stage IV breast cancer could benefit from breast surgery and it might play a more important role in multimodality therapy.
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Affiliation(s)
- Yuxiang Lin
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Kaiyan Huang
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Qiang Zeng
- Department of Pathology, Fujian Medical University First Affiliated Hospital, Fuzhou, Fujian, China
| | - Jie Zhang
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chuangui Song
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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Li M, Wang X, Ma RR, Shi DB, Wang YW, Li XM, He JY, Wang J, Gao P. The Olfactory Receptor Family 2, Subfamily T, Member 6 (OR2T6) Is Involved in Breast Cancer Progression via Initiating Epithelial-Mesenchymal Transition and MAPK/ERK Pathway. Front Oncol 2019; 9:1210. [PMID: 31781505 PMCID: PMC6859866 DOI: 10.3389/fonc.2019.01210] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 10/23/2019] [Indexed: 12/26/2022] Open
Abstract
Breast cancer is the most common female malignancy worldwide, however its molecular pathogenesis still needs in-depth investigation. Here we first revealed that the olfactory receptor family 2, subfamily T, member 6 (OR2T6) was significantly over-expressed in breast cancer tissues compared with normal breast tissues. OR2T6 expression was tightly correlated with higher TNM staging, positive lymph node metastasis, and associated with poorer patients' overall and disease-free survival. And OR2T6 enhanced the proliferation, invasion, and migration ability of breast cancer cell lines in vitro (MCF-7 and MDA-MD-231). Mechanically, it promoted the expression of mesenchymal markers (Vimentin, N-cadherin, and β-catenin) while inhibited E-cadherin expression, suggesting that OR2T6 played a key role in the regulation of epithelial-mesenchymal transition (EMT) process. Moreover, the human gene expression microarray clarified that MAPK/ERK pathway could be initiated by OR2T6 at mRNA level, which was further confirmed at protein level by western blot analysis. Thus, we concluded that OR2T6, as a novel oncogene, contributed to the progression of breast carcinoma by the initiation of EMT and MAPK/ERK pathway.
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Affiliation(s)
- Ming Li
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China.,Department of Pathology, Dezhou People's Hospital, Dezhou, China
| | - Xiao Wang
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China.,Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
| | - Ran-Ran Ma
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China.,Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
| | - Duan-Bo Shi
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China.,Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
| | - Ya-Wen Wang
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China
| | - Xiao-Mei Li
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China
| | - Jun-Yi He
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China.,Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
| | - Jun Wang
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China
| | - Peng Gao
- Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Medicine, Shandong University, Jinan, China.,Department of Pathology, Qilu Hospital, Shandong University, Jinan, China
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Abdelmaksoud BA, Toam MM, Fayed AA. Metronomic capecitabine with aromatase inhibitors for patients with metastatic hormone-receptor positive, HER2-negative breast cancer. BREAST CANCER MANAGEMENT 2019. [DOI: 10.2217/bmt-2019-0012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aim: To evaluate the efficacy and safety of combined metronomic capecitabine with aromatase inhibitors (AIs) for patients with newly diagnosed metastatic hormone-receptor positive, HER2-negative breast cancer. Patients & methods: A total of 41 women with a diagnosis of metastatic hormone-receptor positive, HER2-negative breast cancer received oral metronomic capecitabine, 500 mg/m2 twice daily combined with an AI. Results: After a median follow-up of 24 months (9–50), a median of 15 months of treatment were completed, the median time to progression was 15 months (12.6–17.3) and the median overall survival was 37 months (23.6–50.4). The treatment was tolerated with less than 10% grade 3 toxicities. Conclusion: Combination of metronomic capecitabine and AIs appears to be safe and has encouraging results in advanced hormone-receptor positive, HER2-negative breast cancer.
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Affiliation(s)
- Bader A Abdelmaksoud
- Department of Clinical Oncology & Nuclear Medicine, Faculty of Medicine, Zagazig University, Elgamaa st 44519, Zagazig, Egypt
| | - Mostafa M Toam
- Department of Clinical Oncology & Nuclear Medicine, Faculty of Medicine, Zagazig University, Elgamaa st 44519, Zagazig, Egypt
| | - Alaa A Fayed
- Department of Clinical Oncology & Nuclear Medicine, Faculty of Medicine, Zagazig University, Elgamaa st 44519, Zagazig, Egypt
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Xie BJ, Zhu LN, Ma C, Li JB, Dong L, Zhu ZN, Ding T, Gu XS. A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer. Breast Cancer 2019; 27:186-196. [DOI: 10.1007/s12282-019-01007-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 08/27/2019] [Indexed: 12/28/2022]
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23
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Cagney DN, Lamba N, Montoya S, Li P, Besse L, Martin AM, Brigell RH, Catalano PJ, Brown PD, Leone JP, Tanguturi SK, Haas-Kogan DA, Alexander BM, Lin NU, Aizer AA. Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases. Breast Cancer Res Treat 2019; 176:171-179. [PMID: 30982195 DOI: 10.1007/s10549-019-05236-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 04/10/2019] [Indexed: 11/30/2022]
Abstract
PURPOSE Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms. METHODS We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Patients were stratified by subtype: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), HER2+ positive (HER2+), or triple-negative breast cancer (TNBC). A per-metastasis assessment was conducted. Time-to-event analyses were conducted using multivariable Cox regression. RESULTS Of the 349 patients, 116 had HR+/HER2- subtype, 164 had HER2+ subtype, and 69 harbored TNBC. Relative to HR+/HER2- subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78-5.75, p < 0.001), while patients with TNBC demonstrated higher rates of new brain metastases after initial treatment (HR 3.16, 95% CI 1.99-5.02, p < 0.001) and shorter time to salvage whole brain radiation (WBRT) (HR 3.79, 95% CI 1.36-10.56, p = 0.01) and salvage stereotactic radiation (HR 1.86, 95% CI 1.11-3.10, p = 0.02). CONCLUSIONS We identified a strong association between breast cancer subtype and intracranial recurrence patterns after brain-directed radiation, particularly local progression for HER2+ and distant progression for TNBC patients. If validated, the poorer local control in HER2+ brain metastases may support evaluation of novel local therapy-based approaches, while the increased distant recurrence in TNBC suggests the need for improved systemic therapy and earlier utilization of WBRT.
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Affiliation(s)
- Daniel N Cagney
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
| | | | - Sofia Montoya
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Puyao Li
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Luke Besse
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Allison M Martin
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Rachel H Brigell
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Paul J Catalano
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Paul D Brown
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
| | - Jose P Leone
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Shyam K Tanguturi
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Daphne A Haas-Kogan
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Brian M Alexander
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Nancy U Lin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Ayal A Aizer
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
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Impact of Subtype on Survival of Young Patients With Stage IV Breast Cancer. Clin Breast Cancer 2019; 19:200-207.e1. [PMID: 30795886 DOI: 10.1016/j.clbc.2019.01.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 12/15/2018] [Accepted: 01/19/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Although younger age is a negative prognostic factor for patients with early stage breast cancer, data regarding the outcomes of young patients with stage IV disease are limited. We evaluated differences in overall survival (OS) according to age and disease subtype among patients with stage IV breast cancer. PATIENTS AND METHODS Using Surveillance, Epidemiology, and End Results (SEER) data, we identified 6,302 patients aged < 60 years with de novo stage IV breast cancer between 2010 and 2014. We examined age-specific OS among hormone receptor (HR)-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative (HER2-), HR+/HER2-positive (HER2+), HR-negative (HR-)/HER2+, and triple-negative cases using log-rank tests and Cox proportional hazards models, adjusting for relevant clinical and demographic variables. RESULTS Compared with patients aged 40 to 59 years, patients aged < 40 years (n = 944; 15%) had a higher proportion of HER2+ cancers and a lower proportion of HR+/HER2- disease (P < .001), but a similar proportion of triple-negative disease. Patients aged < 40 years also experienced significantly longer survival, with a median OS of 45 months (vs. 33 months). Further, after stratification by subtype, patients aged < 40 years experienced significantly longer survival, except in the setting of triple-negative disease. These survival differences persisted in adjusted analyses. CONCLUSIONS Compared with those aged 40 to 59 years, patients with de novo metastatic breast cancer aged < 40 years experienced significantly longer survival, except in the setting of triple-negative disease. Distinct treatment-related or biological factors may exist between earlier stage and metastatic breast cancers; further examination of the potential reasons for our findings are warranted.
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25
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Xiao YB, Zhang B, Wu YL. Radiofrequency ablation versus hepatic resection for breast cancer liver metastasis: a systematic review and meta-analysis. J Zhejiang Univ Sci B 2019; 19:829-843. [PMID: 30387333 DOI: 10.1631/jzus.b1700516] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for breast cancer liver metastases (BCLMs). METHODS Studies that had examined the outcomes for both RFA and HR for BCLM were identified by searching the electronic databases PubMed, EMBASE, and the Cochrane Library. Pooled analyzes of the overall survival (OS), disease-free survival (DFS), and short-term outcomes of BCLM were performed. RESULTS Patients with BCLM gained many more survival benefits from HR than from RFA with regard to the 3-year OS rate (combined odds ratio (OR) 0.41, 95% confidence interval (CI) 0.29-0.59, P<0.001), 5-year OS rate (combined OR 0.38, 95% CI 0.32-0.46, P<0.001), 3-year DFS (combined OR 0.36, 95% CI 0.27-0.49, P<0.001), and 5-year DFS (combined OR 0.51, 95% CI 0.40-0.66, P<0.001). RFA had fewer postoperative complications (combined OR 0.30, 95% CI 0.20-0.44, P<0.001) and shorter hospital stays (combined OR -9.01, 95% CI -13.49-4.54, P<0.001) than HR. CONCLUSIONS HR takes precedence over RFA in the treatment of patients with BCLM, considering the better survival rate. RFA gives rise to fewer complications and can be carried out with a shorter hospital stay, compared to HR. RFA should be reserved for patients who are not optimum candidates for resection.
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Affiliation(s)
- Yi-Bin Xiao
- Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Bo Zhang
- Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Yu-Lian Wu
- Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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26
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Ayoub NM, Al-Shami KM, Yaghan RJ. Immunotherapy for HER2-positive breast cancer: recent advances and combination therapeutic approaches. BREAST CANCER-TARGETS AND THERAPY 2019; 11:53-69. [PMID: 30697064 PMCID: PMC6340364 DOI: 10.2147/bctt.s175360] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Cancer immunotherapy has evolved dramatically with improved understanding of immune microenvironment and immunosurveillance. The immunogenicity of breast cancer is rather heterogeneous. Specific subtypes of breast cancer such as estrogen receptor (ER)-negative, human EGF receptor 2 (HER2)-positive, and triple-negative breast cancer (TNBC) have shown evidence of immunogenicity based on tumor–immune interactions. Several preclinical and clinical studies have explored the potential for immunotherapy to improve the clinical outcomes for different subtypes of breast cancer. This review describes the immune microenvironment of HER2-positive breast cancer and summarizes recent clinical advances of immunotherapeutic treatments in this breast cancer subtype. The review provides rationale and ongoing clinical evidence to the use of immune checkpoint inhibitors, therapeutic vaccines, and adoptive T cell immunotherapy in breast cancer. In addition, the present paper describes the most relevant clinical progress of strategies for the combination of immunotherapy with standard treatment modalities in HER2-positive breast cancer including chemotherapy, targeted therapy, and radiotherapy.
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Affiliation(s)
- Nehad M Ayoub
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology (JUST), Irbid, Jordan,
| | - Kamal M Al-Shami
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA
| | - Rami J Yaghan
- Department of General Surgery and Urology, Faculty of Medicine, Jordan University of Science and Technology (JUST), Irbid, Jordan
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Sun D, Lei W, Hou X, Li H, Ni W. PUF60 accelerates the progression of breast cancer through downregulation of PTEN expression. Cancer Manag Res 2019; 11:821-830. [PMID: 30697074 PMCID: PMC6340502 DOI: 10.2147/cmar.s180242] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background PUF60 is a splicing variant of far upstream element binding protein 1-interacting repressor, which is abnormally expressed in a variety of tumors and is closely involved in their progression. However, whether PUF60 participates in the occurrence and development of breast cancer remains unknown. Therefore, the objective of the current study is to explore the effects and mechanism of PUF60 in the progression of breast cancer. Methods PUF60 expression patterns in breast cancer tissues and cells were determined by RT-PCR and Western blotting. The relationship between PUF60 expression and patients' clinical features and outcome was evaluated to assess the potential of PUF60 as a marker for progression and prognosis prediction. CCK-8, flow cytometry, transwell and in vivo tumor formation assays were used to detect cell proliferation, apoptosis, migration, invasion and tumorigenesis. The effects of PUF60 on the activation of PTEN/PI3K/AKT were also evaluated by Western blotting and immunofluorescence assays. Results The expression of PUF60 was elevated in breast cancer tissue samples and cell lines, and its high expression was closely associated with the high incidence of lymph node metastasis and advanced TNM stage. Besides, upregulation of PUF60 with lentivirus infection significantly increased the growth, migration, and invasion and repressed the apoptosis of breast cancer HCC1937 and MDA-MB-231 cells, while silencing of PUF60 with shRNA showed the opposite results. Moreover, PUF60 upregulation promoted the expression of p-AKT, PI3K, and mTOR, while decreased PTEN expression through inhibiting its stability and enhancing its ubiquitination. Furthermore, upregulation of PUF60 promoted the tumorigenesis in vivo, whereas this effect was impaired when PTEN expression was upregulated in MDA-MB-231 and HCC1937 cells. Conclusion This study demonstrates that PUF60 is highly expressed in breast cancer; upregulation of PUF60 accelerates the progression of breast cancer through PTEN inhibition.
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Affiliation(s)
- Dongying Sun
- Department of Medical Imaging, Henan University First Affiliated Hospital, Kaifeng, Henan, China,
| | - Wei Lei
- Department of Medical Imaging, Henan University First Affiliated Hospital, Kaifeng, Henan, China,
| | - Xiaodong Hou
- Department of Medical Imaging, Henan University First Affiliated Hospital, Kaifeng, Henan, China,
| | - Hui Li
- Department of Medical Imaging, Henan University First Affiliated Hospital, Kaifeng, Henan, China,
| | - Wenlu Ni
- Department of Medical Imaging, Henan University First Affiliated Hospital, Kaifeng, Henan, China,
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Sobhani N, Generali D, Zanconati F, Bortul M, Scaggiante B. Current status of PI3K-mTOR inhibition in hormone-receptor positive, HER2-negative breast cancer. World J Clin Oncol 2018; 9:172-179. [PMID: 30622925 PMCID: PMC6314865 DOI: 10.5306/wjco.v9.i8.172] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 10/16/2018] [Accepted: 11/26/2018] [Indexed: 02/06/2023] Open
Abstract
Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments. The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.
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Affiliation(s)
- Navid Sobhani
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Daniele Generali
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Fabrizio Zanconati
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Marina Bortul
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Academic Hospital, Trieste 34149, Italy
| | - Bruna Scaggiante
- Department of Life Sciences, University of Trieste, Trieste 34127, Italy
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Rinnerthaler G, Gampenrieder SP, Petzer A, Burgstaller S, Fuchs D, Rossmann D, Balic M, Egle D, Rumpold H, Singer CF, Bartsch R, Petru E, Melchardt T, Ulmer H, Mlineritsch B, Greil R. Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial). BMC Cancer 2018; 18:1074. [PMID: 30400780 PMCID: PMC6220453 DOI: 10.1186/s12885-018-4979-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 10/21/2018] [Indexed: 12/18/2022] Open
Abstract
Background Triple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy has been approved for TNBC and cytotoxic agents remain the mainstay of treatment. Ixazomib is a selective and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrated. Clinical data are available for carboplatin plus bortezomib in metastatic ovarian and lung cancers showing remarkable antitumor activity and good tolerability (Mol Cancer 11:26 2012, J Thorac Oncol 4:87–92 2009, J Thorac Oncol 7:1032–1040, 2012). Based on this evidence, the phase I/II MBC-10 trial will evaluate the toxicity profile and efficacy of the second-generation proteasome inhibitor ixazomib in combination with carboplatin in patients with advanced TNBC. Methods Patients with metastatic TNBC pretreated with at least one prior line of chemotherapy for advanced disease with a confirmed disease progression and measurable disease according to RECIST criteria 1.1 are eligible for this study. Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle. The phase I part of this study utilizes an alternate dose escalation accelerated titration design. After establishing the maximum tolerated dose (MTD), the efficacy and safety of the combination will be further evaluated (phase II, including 41 evaluable patients). All patients will continue on study drugs until disease progression, unacceptable toxicity or discontinuation for any other reason. Primary endpoint of the phase II is overall response rate, secondary endpoints include progression-free survival, safety, and quality of life. This trial is open for patient enrollment since November 2016 in six Austrian cancer centers. Accrual is planned to be completed within 2 years. Discussion Based on preclinical and clinical findings an ixazomib and carboplatin combination is thought to be effective in metastatic TNBC patients. The MBC-10 trial is accompanied by a broad biomarker program investigating predictive biomarkers for treatment response and potential resistance mechanisms to the investigational drug combination. Trial registration EudraCT Number: 2016–001421-13 received on March 31, 2016, ClinicalTrials.gov Identifier: NCT02993094 first posted on December 15, 2016. This trial was registered prospectively.
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Affiliation(s)
- Gabriel Rinnerthaler
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, 5020, Salzburg, Austria.,Salzburg Cancer Research Institute with Laboratory of Immunological and Molecular Cancer Research and Center for Clinical Cancer and Immunology Trials, Salzburg, Austria.,Cancer Cluster Salzburg, Salzburg, Austria
| | - Simon Peter Gampenrieder
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, 5020, Salzburg, Austria.,Salzburg Cancer Research Institute with Laboratory of Immunological and Molecular Cancer Research and Center for Clinical Cancer and Immunology Trials, Salzburg, Austria.,Cancer Cluster Salzburg, Salzburg, Austria
| | - Andreas Petzer
- Internal Department I for Medical Oncology and Hematology, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria
| | - Sonja Burgstaller
- IVth Department of Internal Medicine with Hematology and Medical Oncolocy, Klinikum Wels-Grieskirchen, Wels, Austria
| | - David Fuchs
- Department of Internal Medicine 3 - Hematology and Oncology, Kepler University Hospital, Linz, Austria
| | - Dieter Rossmann
- 2nd Medical Department, County Hospital Steyr, Steyr, Austria
| | - Marija Balic
- Division of Oncology, Department of Internal Medicine, Medical University Graz, Graz, Austria
| | - Daniel Egle
- Department of Obstetrics and Gynaecology, Innsbruck Medical University, Innsbruck, Austria
| | - Holger Rumpold
- Department of Oncology, Hematology and Gastroenterology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
| | - Christian F Singer
- Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria
| | - Rupert Bartsch
- Department of Internal Medicine 1, Division of Oncology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria
| | - Edgar Petru
- Department of Obstetrics and Gynaecology, Clinical Department of Gynecology, Medical University Graz, Graz, Austria
| | - Thomas Melchardt
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, 5020, Salzburg, Austria.,Salzburg Cancer Research Institute with Laboratory of Immunological and Molecular Cancer Research and Center for Clinical Cancer and Immunology Trials, Salzburg, Austria.,Cancer Cluster Salzburg, Salzburg, Austria
| | - Hanno Ulmer
- Department of Medical Statistics and Informatics, Medical University Innsbruck, Innsbruck, Austria
| | - Brigitte Mlineritsch
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, 5020, Salzburg, Austria.,Salzburg Cancer Research Institute with Laboratory of Immunological and Molecular Cancer Research and Center for Clinical Cancer and Immunology Trials, Salzburg, Austria.,Cancer Cluster Salzburg, Salzburg, Austria
| | - Richard Greil
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, 5020, Salzburg, Austria. .,Salzburg Cancer Research Institute with Laboratory of Immunological and Molecular Cancer Research and Center for Clinical Cancer and Immunology Trials, Salzburg, Austria. .,Cancer Cluster Salzburg, Salzburg, Austria.
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30
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Blancas I, Aguirre E, Morales S, Gonzálvez ML, Servitja S, Díaz N, Del Barco S, Barnadas A, Margelí M, García Carbonero I, Llombart A. Real-world data on the efficacy and safety of weekly oral vinorelbine in breast cancer patients previously treated with anthracycline or taxane-based regimens. Clin Transl Oncol 2018; 21:459-466. [PMID: 30293232 DOI: 10.1007/s12094-018-1946-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 09/05/2018] [Indexed: 01/29/2023]
Abstract
PURPOSE To evaluate the efficacy and safety of oral weekly vinorelbine 60 mg/m2 for metastatic breast cancer (MBC) in patients previously treated with anthracyclines or taxanes in routine clinical practice. MATERIALS AND METHODS Fifty-five patients were enrolled in a prospective multicentre study conducted in Spain. Women ≥ 18 years of age with locally advanced breast cancer who were not candidates for surgical treatment with a radical intention or patients with stage IV disease, and who had received a prior taxane or anthracycline regimen were eligible for participation. RESULTS Median age was 67 years. Median progression-free survival was 3.7 months (95% CI 2.5-4.9), median overall survival 10 months (95% CI 6.6-13.5), and overall response rate and clinical benefit rate were 29.1% and 49.1%, respectively. Main grade 3 and 4 toxicities were neutropenia 9.1%, febrile neutropenia 3.6% and constipation 3.6%. In total, 86% of the patients received complete treatment without delays or dose reduction. Moreover, HER2-positive patients who received oral vinorelbine concomitantly with trastuzumab showed better response (complete response: HER2-positive 14.3% vs. HER2-negative 0%; partial response: HER2-positive 42.9% vs. HER2-negative 25.6%; p = 0.008), better disease control rate (HER2-positive 100% vs. HER2-negative 46.2%; p = 0.011), and better values for the remaining analysed variables than HER2-negative patients. CONCLUSION Our study provides real-world data on the use of oral weekly vinorelbine, which proves an effective and well-tolerated regimen for MBC patients previously treated with taxanes or anthracyclines. Patients with HER2-positive disease could also benefit from this treatment in combination with trastuzumab.
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Affiliation(s)
- I Blancas
- Department of Medical Oncology, University Hospital San Cecilio, Av. De la Investigación s/n, 18016, Granada, Spain.
| | - E Aguirre
- Department of Medical Oncology, University Hospital Arnau de Vilanova, Lleida, Spain
| | - S Morales
- Department of Medical Oncology, University Hospital Arnau de Vilanova, Lleida, Spain
| | - M L Gonzálvez
- Department of Medical Oncology, University Hospital Arrixaca, Murcia, Spain
| | - S Servitja
- Department of Medical Oncology, Hospital Del Mar, Barcelona, Spain
| | - N Díaz
- Department of Medical Oncology, University Hospital San Juan de Alicante, Alicante, Spain
| | - S Del Barco
- Department of Medical Oncology, Institut Català d'Oncologia, Girona, Spain
| | - A Barnadas
- Department of Medical Oncology, University Hospital Sant Pau, Barcelona, Spain
| | - M Margelí
- Department of Medical Oncology, Institut Català d'Oncologia, Badalona, Spain
| | - I García Carbonero
- Department of Medical Oncology, Virgen de La Salud Hospital, Toledo, Spain
| | - A Llombart
- Department of Medical Oncology, Arnau de Vilanova Hospital, Valencia, Spain
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Sobhani N, Corona SP, Bonazza D, Ianza A, Pivetta T, Roviello G, Cortale M, Guglielmi A, Zanconati F, Generali D. Advances in systemic therapy for malignant mesothelioma: future perspectives. Future Oncol 2017; 13:2083-2101. [PMID: 28984470 DOI: 10.2217/fon-2017-0224] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 06/29/2017] [Indexed: 11/21/2022] Open
Abstract
Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.
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Affiliation(s)
- Navid Sobhani
- Department of Medical, Surgical, & Health Sciences, University of Trieste, Piazza Ospitale 1 34129 Trieste, Italy
- Department of Medical, Surgical, & Health Sciences, Teaching Hospital of Cattinara, University of Trieste, Via Fiume 447, 34129 Trieste, Italy
| | - Silvia Paola Corona
- Department of Radiation Oncology, Peter MacCallum Cancer Center, Moorabbin Campus, 823-865 Centre Rd, Bentleigh East VIC 3165, Australia
| | - Deborah Bonazza
- Department of Medical, Surgical, & Health Sciences, Teaching Hospital of Cattinara, University of Trieste, Via Fiume 447, 34129 Trieste, Italy
| | - Anna Ianza
- Department of Medical, Surgical, & Health Sciences, University of Trieste, Piazza Ospitale 1 34129 Trieste, Italy
| | - Tania Pivetta
- Department of Medical, Surgical, & Health Sciences, Teaching Hospital of Cattinara, University of Trieste, Via Fiume 447, 34129 Trieste, Italy
| | | | - Maurizio Cortale
- Department of Medical, Surgical, & Health Sciences, Teaching Hospital of Cattinara, University of Trieste, Via Fiume 447, 34129 Trieste, Italy
| | - Alessandra Guglielmi
- Department of Medical, Surgical, & Health Sciences, University of Trieste, Piazza Ospitale 1 34129 Trieste, Italy
| | - Fabrizio Zanconati
- Department of Medical, Surgical, & Health Sciences, Teaching Hospital of Cattinara, University of Trieste, Via Fiume 447, 34129 Trieste, Italy
| | - Daniele Generali
- Department of Medical, Surgical, & Health Sciences, University of Trieste, Piazza Ospitale 1 34129 Trieste, Italy
- Breast Cancer Unit, ASST Cremona, Viale Concordia 1, 26100, Cremona, Italy
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32
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Benedetti R, Dell’Aversana C, Giorgio C, Astorri R, Altucci L. Breast Cancer Vaccines: New Insights. Front Endocrinol (Lausanne) 2017; 8:270. [PMID: 29081765 PMCID: PMC5645504 DOI: 10.3389/fendo.2017.00270] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 09/26/2017] [Indexed: 01/07/2023] Open
Abstract
Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and recurrence with different modalities. Despite these relatively wide chances, also used in combinatory protocols, relevant mortality and relapse rates, often associated with resistant phenotypes, stress the need for a personalized-medicine based on prompting the patient's immune system (IS) against cancer cells. BC immunogenicity was latterly proven, so the whole immunotherapy field for BC is still at a very early stage. This immunotherapeutic approach exploits both the high specificity of adaptive immune response and the immunological memory. This review is focused on some of the majorly relevant BC vaccines available (NeuVax, AVX901, and INO-1400), providing a description of the more promising clinical trials. The efficacy of cancer vaccines highly depends on the patient's IS, and a wide optimization is needed in terms of targets' selection, drug design and combinations, dose finding, protocol structuring, and patients' recruitment; moreover, new standards are being discussed for the outcome evaluation. However, early-phases excellent results suggest that the manipulation of the IS via specific vaccines is a highly attractive approach for BC.
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Affiliation(s)
- Rosaria Benedetti
- Dipartimento di Biochimica Biofisica e Patologia generale, Università degli Studi della Campania ‘L. Vanvitelli’ Naples, Naples, Italy
- *Correspondence: Rosaria Benedetti, ; Lucia Altucci,
| | - Carmela Dell’Aversana
- Dipartimento di Biochimica Biofisica e Patologia generale, Università degli Studi della Campania ‘L. Vanvitelli’ Naples, Naples, Italy
| | - Cristina Giorgio
- Dipartimento di Biochimica Biofisica e Patologia generale, Università degli Studi della Campania ‘L. Vanvitelli’ Naples, Naples, Italy
| | - Roberta Astorri
- Dipartimento di Biochimica Biofisica e Patologia generale, Università degli Studi della Campania ‘L. Vanvitelli’ Naples, Naples, Italy
- Dipartimento di Medicina e Scienze della Salute “Vincenzo Tiberio”, Università degli Studi del Molise, Campobasso, Italy
| | - Lucia Altucci
- Dipartimento di Biochimica Biofisica e Patologia generale, Università degli Studi della Campania ‘L. Vanvitelli’ Naples, Naples, Italy
- *Correspondence: Rosaria Benedetti, ; Lucia Altucci,
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