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Lafci O, Resch D, Santonocito A, Clauser P, Helbich T, Baltzer PAT. Role of imaging based response assesment for adapting neoadjuvant systemic therapy for breast cancer: A systematic review. Eur J Radiol 2025; 187:112105. [PMID: 40252279 DOI: 10.1016/j.ejrad.2025.112105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/21/2025]
Abstract
PURPOSE The objective of this systematic review is to investigate the role of imaging in response monitoring during neoadjuvant systemic therapy (NST) for breast cancer and assess whether treatment modifications based on imaging response are implemented in clinical practice. METHODS A systematic review was conducted, analyzing five clinical practice guidelines and 147 clinical trial publications involving NST for breast cancer. The snowballing technique was employed, using a "start set" of clinical guidelines to trace relevant trials. Additionally, a PubMed search was conducted to identify trials published between 2023-2024. The review analyzed the use of imaging modalities, timing, and response criteria, and whether escalation, de-escalation, or change of treatment occurred based on imaging response. RESULTS Imaging was utilized in 81 % (119/147) of the trials, with ultrasound, MRI, and mammography being the most frequently employed modalities. Mid-treatment imaging was applied in 56 % (83/147) of the trials. However, only 15 % (22/147) of the trials implemented treatment modifications based on imaging response, highlighting the limited application of imaging response-guided therapy. No standardized imaging protocols or consistent response-guided treatment strategies were identified across the trials or clinical practice guidelines, with considerable variability in imaging methods, timing, and response criteria. CONCLUSION This systematic review underscores the critical need for standardized imaging protocols, response assessment criteria and image-guided treatment decisions. It is therefore evident that imaging for response monitoring during treatment should preferably be performed within clinical trials.
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Affiliation(s)
- Oguz Lafci
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Daphne Resch
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Ambra Santonocito
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Paola Clauser
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Thomas Helbich
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria
| | - Pascal A T Baltzer
- Division of General and Pediatric Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.
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Han HS, Aldrich AL, Garg SK, Weinfurtner RJ, Nguyen JV, Mo Q, Whiting J, Childress J, Soliman H, Costa R, Armaghani A, Soyano A, Kiluk J, Hoover S, Lee MC, Khakpour N, Shenoi N, Jameel Z, Koski GK, Czerniecki BJ. Alteration of the Tumor Microenvironment With Intratumoral Dendritic Cells Before Chemotherapy in ERBB2 Breast Cancer: A Nonrandomized Clinical Trial. JAMA Oncol 2025; 11:119-127. [PMID: 39636623 PMCID: PMC11622104 DOI: 10.1001/jamaoncol.2024.5371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 09/12/2024] [Indexed: 12/07/2024]
Abstract
Importance Current chemotherapy regimens for patients with ERBB2 (formerly HER2)-positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies. Objective To evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with ERBB2-targeted therapies. Design, Setting, and Participants This phase 1 (lead-in phase of a single-center phase 2 trial) nonrandomized clinical trial was conducted at Moffitt Cancer Center (Tampa, Florida). Patients were enrolled from October 2021 to October 2022. Data were analyzed in 2023 Patients with early-stage ERBB2-positive breast cancer with tumors 1 cm or larger were eligible. Interventions Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m2, intravenously, 12 times weekly. Trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) were administered intravenously every 3 weeks for 6 cycles starting from day 1 of cDC1 injections. Two dose levels (DLs) of IT cDC1 (DL1 = 50 million and DL2 = 100 million cells) were evaluated, including 6 patients in each DL. Main Outcomes and Measures The primary outcomes were the safety and immune response, and the secondary outcomes were the antitumor efficacy as measured by breast magnetic resonance imaging and residual cancer burden at surgery following neoadjuvant therapy. Results Twelve ERBB2-positive patients were enrolled and received treatment (DL1 = 6 and DL2 = 6). Nine patients had hormone receptor-positive disease and 3 had hormone receptor-negative disease, with clinical stage I (n = 5), II (n = 4), and III (n = 3). The most frequently observed adverse events with cDC1 were grade 1 to 2 chills (50%), fatigue (41.7%), headache (33%), and injection site reactions (33%). DL2 was associated with a diminished anti-ERBB2 CD4 T-helper 1 blood response with a concomitant increase in innate and adaptive responses within the tumor. Preimmunotherapy and postimmunotherapy breast magnetic resonance imaging results showed 9 objective responses, 6 partial responses, 3 complete responses, and 3 stable diseases. Following surgery, 7 patients had a pathologic complete response. Conclusions and Relevance In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose. Trial Registration ClinicalTrials.gov Identifier: NCT05325632.
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Affiliation(s)
- Hyo S. Han
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Amy L. Aldrich
- Clinical Science Division, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Saurabh K. Garg
- Clinical Science Division, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - R. Jared Weinfurtner
- Diagnostic Imaging, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Jonathan V. Nguyen
- Advanced Analytical and Digital Laboratory, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Qianxing Mo
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Junmin Whiting
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Jennifer Childress
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Hatem Soliman
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Ricardo Costa
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Avan Armaghani
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Aixa Soyano
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - John Kiluk
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Susan Hoover
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Marie C. Lee
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Nazanin Khakpour
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Nithin Shenoi
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Zena Jameel
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Gary K. Koski
- Department of Biological Sciences, Kent State University, Kent, Ohio
| | - Brian J. Czerniecki
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
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Gao Z, Xu J, Wang Y, Wu J, Sun T. Case Report: Effective Treatment With Pyrotinib and Capecitabine in a Heavily Pretreated Locally Advanced Breast Cancer Harboring Both HER2 Overexpression and Mutant. Front Oncol 2021; 11:715554. [PMID: 34722261 PMCID: PMC8553255 DOI: 10.3389/fonc.2021.715554] [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: 05/28/2021] [Accepted: 09/16/2021] [Indexed: 11/13/2022] Open
Abstract
The prognosis for female patients with locally advanced breast cancer (LABC) has improved with the emergence of novel drugs, especially for those who have HER2 overexpression or ERBB-2 amplification. Trastuzumab-based regimen has been the paradigm in guidelines as first-line therapy, whereas many patients got progressive disease after several cycles of treatment or rapidly progress because of primary resistance. Point mutations of ERBB2 gene occur in both HER2-amplication and non-amplification patients, with a 2% ratio in HER2 non-amplification cohort and 1.48% in HER2 amplication population. The acquired mutation ratio of ERBB2 substantially raised to 16.7%–17.7% in patients prior to trastuzumab treatment. ERBB2 mutation may be a critical reason of resistance and disease progression among the patients treated with anti-HER2 monoclonal trastuzumab or dual anti-HER2 antibodies with trastuzumab and pertuzumab, or tyrosine-kinase inhibitor. ERBB-2 mutation with L755S and V842I indicates resistance to trastuzumab, while that with L755S and K753I indicates resistance to lapatinib; these mutations maybe sensitive to pan-HER tyrosine-kinase inhibitors. A 48-year woman diagnosed with HER2-positive LABC developed trastuzumab resistance after three lines of trastuzumab cross-line treatment with partial response (PR) as the best response. The tissue was performed by next-generation sequencing (NGS), and the results discovered L755S in ERBB2 gene. Then, she received effective treatment with pyrotinib plus capecitabine and underwent mastectomy after six cycles of combined treatment with PR. Subsequently, breast mastectomy was performed, and she took pyrotinib plus capecitabine for 1 year and pyrotinib monotherapy for another 1 year as adjuvant therapy and achieved a long-term clinical benefit. In conclusion, pyrotinib is a potential neoadjuvant agent for patients who are heavily pretreated and harbor both ERBB2 amplification and ERBB2 mutant in locally advanced breast cancer.
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Affiliation(s)
- Zhichao Gao
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Junnan Xu
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Yan Wang
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Jie Wu
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Tao Sun
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.,Department of Breast Medicine, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, China
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Chowdhury P, Ghosh U, Samanta K, Jaggi M, Chauhan SC, Yallapu MM. Bioactive nanotherapeutic trends to combat triple negative breast cancer. Bioact Mater 2021; 6:3269-3287. [PMID: 33778204 PMCID: PMC7970221 DOI: 10.1016/j.bioactmat.2021.02.037] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 02/27/2021] [Accepted: 02/28/2021] [Indexed: 02/09/2023] Open
Abstract
The management of aggressive breast cancer, particularly, triple negative breast cancer (TNBC) remains a formidable challenge, despite treatment advancement. Although newer therapies such as atezolizumab, olaparib, and sacituzumab can tackle the breast cancer prognosis and/or progression, but achieved limited survival benefit(s). The current research efforts are aimed to develop and implement strategies for improved bioavailability, targetability, reduce systemic toxicity, and enhance therapeutic outcome of FDA-approved treatment regimen. This review presents various nanoparticle technology mediated delivery of chemotherapeutic agent(s) for breast cancer treatment. This article also documents novel strategies to employ cellular and cell membrane cloaked (biomimetic) nanoparticles for effective clinical translation. These technologies offer a safe and active targeting nanomedicine for effective management of breast cancer, especially TNBC.
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Affiliation(s)
- Pallabita Chowdhury
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Upasana Ghosh
- Department of Biomedical Engineering, School of Engineering, Rutgers University, The State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Kamalika Samanta
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Meena Jaggi
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Subhash C. Chauhan
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Murali M. Yallapu
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
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Tesch ME, Gelmon KA. Targeting HER2 in Breast Cancer: Latest Developments on Treatment Sequencing and the Introduction of Biosimilars. Drugs 2021; 80:1811-1830. [PMID: 33021725 DOI: 10.1007/s40265-020-01411-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Approximately 20% of all breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). Targeting breast cancer through this vital oncogenic protein has been a major step towards improved patient outcomes. Today, several anti-HER2 agents are in clinical use including: the monoclonal antibodies trastuzumab and pertuzumab; the small molecule inhibitors lapatinib, neratinib, and tucatinib; and the antibody-drug conjugates ado-trastuzumab emtansine and trastuzumab deruxtecan, in some jurisdictions. In addition, several trastuzumab biosimilars have recently been granted regulatory approval in North America and the EU, and are enhancing patient access to HER2-directed therapy. The various agents differ greatly in their side-effect profiles and approved indications, from neoadjuvant and adjuvant use in early disease, to first- and later-line use in metastatic disease. This review discusses the current treatment recommendations for the use of anti-HER2 agents alone and in combination, examines the latest advances in HER2-targeted drugs and how they may be best applied in clinical practice, and provides guidance on optimal sequencing of the growing array of therapeutic options for HER2-positive breast cancer.
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Affiliation(s)
- Megan E Tesch
- Department of Medical Oncology, British Columbia Cancer, 600 W. 10th Avenue, Vancouver, BC, V5Z 4E6, Canada
| | - Karen A Gelmon
- Department of Medical Oncology, British Columbia Cancer, 600 W. 10th Avenue, Vancouver, BC, V5Z 4E6, Canada.
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Jagosky M, Tan AR. Combination of Pertuzumab and Trastuzumab in the Treatment of HER2-Positive Early Breast Cancer: A Review of the Emerging Clinical Data. BREAST CANCER-TARGETS AND THERAPY 2021; 13:393-407. [PMID: 34163239 PMCID: PMC8213954 DOI: 10.2147/bctt.s176514] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 03/23/2021] [Indexed: 01/03/2023]
Abstract
Human epidermal growth factor receptor type 2 (HER2) is a relevant and effective target in breast cancer. The development of monoclonal antibodies against HER2 has revolutionized the treatment of HER2-positive breast cancer. The humanized monoclonal antibody, trastuzumab, was the first in its class to be widely adopted. It was initially studied in the metastatic setting and then in the treatment of early-stage disease, demonstrating significant improvement in overall survival in both settings. The addition of pertuzumab further improved upon results achieved with trastuzumab and chemotherapy, specifically extending overall survival in patients with metastatic disease, lessening the risk of recurrence when used in the adjuvant setting, and improving pathologic complete response rate when utilized in the neoadjuvant setting. In this article, we review the studies that support the use of HER2-directed monoclonal antibodies in early-stage breast cancer both in the adjuvant and neoadjuvant settings and focus on the success of dual HER2-targeted therapy achieved with the combination of trastuzumab and pertuzumab. A newer way to administer these agents, specifically the subcutaneous formulation of pertuzumab and trastuzumab with recombinant human hyaluronidase, will also be discussed.
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Affiliation(s)
- Megan Jagosky
- Department of Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Antoinette R Tan
- Department of Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
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7
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Lopresti ML, Bian JJ, Sakr BJ, Strenger RS, Legare RD, Fenton M, Witherby SM, Dizon DS, Pandya SV, Stuckey AR, Edmondson DA, Gass JS, Emmick CM, Graves TA, Cutitar M, Olszewski AJ, Sikov WM. Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study. Breast Cancer Res Treat 2021; 189:93-101. [PMID: 34086171 DOI: 10.1007/s10549-021-06266-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 05/18/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. METHODS Patients with clinical stage II-III HER2+ BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. RESULTS In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade ≥ 3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade ≥ 2 diarrhea (40%) than the standard loading dose (60%). CONCLUSION pCR rates with our regimen were as high as reported with TCHP with fewer grade ≥ 3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+ BC. TRAIL REGISTRATION ClinicalTrials.gov identifier: NCT02789657.
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Affiliation(s)
- M L Lopresti
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - J J Bian
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA.,Division of Hematology-Oncology, Maine Medical Center, Portland, ME, USA
| | - B J Sakr
- Department of Obstetrics & Gynecology, Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - R S Strenger
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - R D Legare
- Department of Obstetrics & Gynecology, Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - M Fenton
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - S M Witherby
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - D S Dizon
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - S V Pandya
- Department of Obstetrics & Gynecology, Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.,Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - A R Stuckey
- Department of Obstetrics & Gynecology, Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - D A Edmondson
- Department of Obstetrics & Gynecology, Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - J S Gass
- Department of Obstetrics & Gynecology, Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - C M Emmick
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - T A Graves
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - M Cutitar
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - A J Olszewski
- Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA
| | - W M Sikov
- Department of Obstetrics & Gynecology, Program in Women's Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA. .,Breast Health Center, 101 Dudley Street, Providence, RI, 02905, USA.
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8
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Abstract
PURPOSE OF REVIEW Breast cancer is a collection of diseases including the more common invasive ductal and lobular carcinomas and rarer subtypes of breast cancer. This review summarizes the features of rare breast cancers. RECENT FINDINGS Each of the rare tumors has defined pathological and clinical features that impact treatment recommendations. In this review, we summarize these for each rare type of breast cancer and where available we include molecular features of each tumor. Rare subtypes of breast cancer each have unique features. In many cases, data is limited for the optimal treatment approaches.
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Affiliation(s)
- Sarah Jenkins
- Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
- Medical Oncology Service, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
| | - Megan E Kachur
- Pathology Department, Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA
| | - Kamil Rechache
- Medical Oncology Service, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
| | - Justin M Wells
- Pathology Department, Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA.
| | - Stanley Lipkowitz
- Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
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Wang Y, Singh K, Dizon D, Graves T, Amin A, Yakirevich E. Immunohistochemical HER2 score correlates with response to neoadjuvant chemotherapy in HER2-positive primary breast cancer. Breast Cancer Res Treat 2021; 186:667-676. [PMID: 33598878 DOI: 10.1007/s10549-021-06124-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 02/01/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE The accuracy of biomarker assessment in breast cancer (BC) is paramount for therapy decisions and informs prognosis. We investigated neoadjuvant chemotherapy (NAC) response in HER2-positive BC with respect to immunohistochemistry (IHC) and in situ hybridization (ISH) results. We aimed to determine the role of HER2 protein expression in predicting NAC response and long-term outcome in two HER2-positive groups: IHC 3 + versus IHC 2 + ISH amplified groups. METHODS This retrospective study included 192 consecutive HER2 + primary BCs diagnosed from 2007 to 2019 treated with NAC and HER2-targeted agent (NACH). There were 158 HER2 3 + and 34 HER2 2 + ISH + cases. Clinicopathological parameters and long-term outcomes were analyzed. RESULTS The Pathological Complete Response (pCR) rate was 85.7% (72/84) in ER-/HER2 + BCs and was lower in ER + /HER2 + BCs (42.6%, 46/108). The pCR was 55.1% (86/156) in the HER2 3 + group and was only 17.6% in HER2 2 + ISH + group (p < 0.001). Patients who achieved pCR in HER2 2 + ISH + group did not show a significantly higher HER2/CEP17 ratio or HER2 copy number. The overall survival (OS) and progression-free survival (PFS) were significantly higher in pCR compared to non-pCR cases (p = 0.011 and p = 0.015, respectively). CONCLUSIONS There is significant heterogeneity in response to the NACH regimens in HER2 + cases. Our findings indicate that HER2 IHC score and ER expression determine NACH response in HER2 + BC. We recommend considering HER2 protein expression and ISH value to better select patients and assess the response for HER2-targeted therapy.
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Affiliation(s)
- Yihong Wang
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, 593 Eddy St, APC 12, Providence, RI, 02903, USA.
| | - Kamaljeet Singh
- Department of Pathology and Laboratory Medicine, Women and Infant Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA
| | - Don Dizon
- Department of Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA
| | - Teresa Graves
- Department of Surgery, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA
| | - Ali Amin
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, 593 Eddy St, APC 12, Providence, RI, 02903, USA
| | - Evgeny Yakirevich
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, 593 Eddy St, APC 12, Providence, RI, 02903, USA
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10
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Sardesai S, Badawi M, Mrozek E, Morgan E, Phelps M, Stephens J, Wei L, Kassem M, Ling Y, Lustberg M, Stover D, Williams N, Layman R, Reinbolt R, VanDeusen J, Cherian M, Grever M, Carson W, Ramaswamy B, Wesolowski R. A phase I study of an oral selective gamma secretase (GS) inhibitor RO4929097 in combination with neoadjuvant paclitaxel and carboplatin in triple negative breast cancer. Invest New Drugs 2020; 38:1400-1410. [PMID: 31953695 DOI: 10.1007/s10637-020-00895-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 01/10/2020] [Indexed: 12/20/2022]
Abstract
Upregulation of Notch pathway is associated with poor prognosis in breast cancer. We present the results of a phase I study of an oral selective gamma secretase (GS) inhibitor (critical to Notch signaling), RO4929097 in combination with neoadjuvant chemotherapy for operable triple negative breast cancer. The primary objective was to determine the maximum tolerated dose (MTD) of RO4929097. Secondary objectives were to determine real-time pharmacokinetics of RO4929097 and paclitaxel, safety and pathologic (pCR) complete response to study treatment. Eligible patients, initiated carboplatin at AUC 6 administered intravenously (IV) on day 1, weekly paclitaxel at 80 mg/m2 IV and RO4929097 10 mg daily given orally (PO) on days 1-3, 8-10 and 15-17 for six 21-day cycles. RO4929097 was escalated in 10 mg increments using the 3 + 3 dose escalation design. Two DLTs were observed in 14 patients - Grade (G) 4 thrombocytopenia in dose level 1 (10 mg) and G3 hypertension in dose level 2 (20 mg). Protocol-defined MTD was not determined due to discontinuation of RO4929097 development. However, 4 of 5 patients enrolled to 20 mg dose of RO4929097 required dose reduction to 10 mg due to toxicities (including neutropenia, thrombocytopenia and hypertension) occurring during and beyond the DLT observation period. Thus, 10 mg would have been the likely dose level for further development. G3 or higher hematologic toxicities included neutropenia (N = 8, 57%) and thrombocytopenia (N = 5, 36%) patients. Six (43%) patients had G2-3 neuropathy requiring paclitaxel dose reduction. No signs of drug-drug interaction between paclitaxel and RO4929097 were evident. Five patients (36%) had pCR.
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Affiliation(s)
- Sagar Sardesai
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Mohamed Badawi
- The Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Ewa Mrozek
- Medical Oncology, Mercy Health, St. Rita's Cancer Center, Lima, OH, USA
| | - Evan Morgan
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Mitch Phelps
- The Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Julie Stephens
- Medical Oncology, Mercy Health, St. Rita's Cancer Center, Lima, OH, USA
| | - Lai Wei
- The Center for Biostatistics, Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Mahmoud Kassem
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Yonghua Ling
- The Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Maryam Lustberg
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Daniel Stover
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Nicole Williams
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Rachel Layman
- Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Raquel Reinbolt
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Jeffrey VanDeusen
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Mathew Cherian
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Michael Grever
- The Division of Hematology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - William Carson
- The Division of Surgical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Bhuvaneswari Ramaswamy
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Robert Wesolowski
- The Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA.
- The Ohio State University Comprehensive Cancer Center, Suite 1204, Lincoln Tower, 1800 Cannon Drive, Columbus, OH, 43210, USA.
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11
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Rastelli F, Biancanelli S, Falzetta A, Martignetti A, Casi C, Bascioni R, Giustini L, Crispino S. Triple-Negative Breast Cancer: Current State of the Art. TUMORI JOURNAL 2018. [DOI: 10.1177/548.6505] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Francesca Rastelli
- Oncology Unit Zona Territoriale 11, Ospedale “Murri”, Azienda Sanitaria Unica Regionale Marche, Fermo
| | | | | | | | | | - Romeo Bascioni
- Oncology Unit Zona Territoriale 11, Ospedale “Murri”, Azienda Sanitaria Unica Regionale Marche, Fermo
| | - Lucio Giustini
- Oncology Unit Zona Territoriale 11, Ospedale “Murri”, Azienda Sanitaria Unica Regionale Marche, Fermo
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12
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Omarini C, Guaitoli G, Pipitone S, Moscetti L, Cortesi L, Cascinu S, Piacentini F. Neoadjuvant treatments in triple-negative breast cancer patients: where we are now and where we are going. Cancer Manag Res 2018; 10:91-103. [PMID: 29391830 PMCID: PMC5772398 DOI: 10.2147/cmar.s146658] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Triple-negative breast cancer (TNBC) remains the poorest-prognosis breast cancer (BC) subtype. Gene expression profiling has identified at least six different triple-negative subtypes with different biology and sensitivity to therapies. The heterogeneous nature of TN tumors may justify the difficulty in treating this BC subtype. Several targeted agents have been investigated in clinical trials without demonstrating a clear survival benefit. Therefore, systemic chemotherapy remains the cornerstone of current clinical practice. Improving the knowledge of tumor biology is mandatory for patient management. In stages II and III, neoadjuvant systemic treatment is an effective option of care. The achievement of a pathological complete response represents an optimal surrogate for survival outcome as well as a test for tumor drug sensitivity. In this review, we provide a brief description of the main predictive biomarkers for tumor response to systemic treatment. Moreover, we review the treatment strategies investigated for TNBCs in neoadjuvant settings focusing on experimental drugs such as immunotherapy and poly [ADP-ribose] polymerase inhibitors that hold promise in the treatment of this aggressive disease. Therefore, the management of TNBC represents an urgent, current, unmet need in daily clinical practice. A key recommendation is to design biology-driven clinical trials wherein TNBC patients may be treated on the basis of tumor molecular profile.
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Affiliation(s)
- Claudia Omarini
- Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy
| | - Giorgia Guaitoli
- Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy
| | - Stefania Pipitone
- Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy
| | - Luca Moscetti
- Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy
| | - Laura Cortesi
- Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy
| | - Stefano Cascinu
- Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy
| | - Federico Piacentini
- Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy
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13
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Gluz O, Nitz U, Liedtke C, Christgen M, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Bangemann N, Lindner C, Kuemmel S, Clemens M, Potenberg J, Staib P, Kohls A, von Schumann R, Kates R, Kates R, Schumacher J, Wuerstlein R, Kreipe HH, Harbeck N. Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results. J Natl Cancer Inst 2017; 110:628-637. [PMID: 29228315 DOI: 10.1093/jnci/djx258] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 11/08/2017] [Indexed: 01/02/2023] Open
Affiliation(s)
- Oleg Gluz
- Moenchengladabach, West German Study Group
- Moenchengladbach, Breast Center Niederrhein, Evangelical Hospital Johanniter Bethesda
- University Clinics Cologne
| | - Ulrike Nitz
- Moenchengladabach, West German Study Group
- Moenchengladbach, Breast Center Niederrhein, Evangelical Hospital Johanniter Bethesda
| | - Cornelia Liedtke
- Department of Gynecology and Obstetrics, University Clinics Schleswig-Holstein/Campus Luebeck
| | | | | | | | | | - Mathias Warm
- Breast Center, City Hospital of Cologne Holweide
| | | | | | - Bahriye Aktas
- Department of Gynecology and Obstetrics, University Clinics Essen
- Department of Gynecology, University Hospital Leipzig
| | | | | | - Christoph Lindner
- Clinic of Gynecology, Charité University Clinics Berlin
- Department of Gynecology and Obstetrics, Agaplesion Diakonie Clinic
| | | | | | | | - Peter Staib
- Department of Oncology, St. Antonius Hospital
| | - Andreas Kohls
- Department of Gynecology and Obstetrics, Evangelical Hospital Ludwigsfelde
| | - Raquel von Schumann
- Moenchengladbach, Breast Center Niederrhein, Evangelical Hospital Johanniter Bethesda
| | | | | | | | - Rachel Wuerstlein
- Breast Center, University of Munich (LMU) and CCCLMU, Munich, Germany
| | | | - Nadia Harbeck
- Moenchengladabach, West German Study Group
- Breast Center, University of Munich (LMU) and CCCLMU, Munich, Germany
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14
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Huang L, Liu Q, Chen S, Shao Z. Cisplatin versus carboplatin in combination with paclitaxel as neoadjuvant regimen for triple negative breast cancer. Onco Targets Ther 2017; 10:5739-5744. [PMID: 29238206 PMCID: PMC5716301 DOI: 10.2147/ott.s145934] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background Platinum salts have demonstrated sufficient efficacy and safety for consideration of their use in a neoadjuvant setting for triple negative breast cancer (TNBC). Patients and methods We retrospectively analyzed 145 TNBC cases to compare the activity and tolerability of cisplatin and carboplatin. Two groups received weekly paclitaxel and platinum salts. Results In total, 87% of patients in the cisplatin group and 82% of patients in the carboplatin group experienced a clinical objective response after four cycles (complete response or partial response; P=0.570). Pathological complete response (pCR) occurred similarly in the cisplatin group and the carboplatin group (44% versus 42%, P=0.789). In survival analysis, there was no difference between the two regimens. The most common grade 3/4 adverse events were neutropenia and leukopenia. Conclusion There was no significant difference between the groups in terms of adverse events. Both types of platinum salts and weekly paclitaxel are feasible therapies that achieved high pCR rates and tolerability in TNBC patients.
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Affiliation(s)
- Liang Huang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qi Liu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Radiation Oncology, Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, China
| | - Sheng Chen
- Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiming Shao
- Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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15
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Saloustros E, Nikolaou M, Kalbakis K, Polyzos A, Christofillakis C, Kentepozidis N, Pistamaltzian N, Kourousis C, Vamvakas L, Georgoulias V, Mavroudis D. Weekly Paclitaxel and Carboplatin Plus Bevacizumab as First-Line Treatment of Metastatic Triple-Negative Breast Cancer. A Multicenter Phase II Trial by the Hellenic Oncology Research Group. Clin Breast Cancer 2017; 18:88-94. [PMID: 29153775 DOI: 10.1016/j.clbc.2017.10.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 09/03/2017] [Accepted: 10/16/2017] [Indexed: 11/29/2022]
Abstract
BACKGROUND Triple-negative breast cancer (TNBC) lacks a standard targeted therapeutic strategy and is treated with conventional cytotoxic agents. Because of the sensitivity of TNBC to platinum compounds and the synergistic effect of bevacizumab with paclitaxel we investigated the efficacy and toxicity of weekly paclitaxel and carboplatin in combination with bevacizumab as first-line treatment in metastatic TNBC. PATIENTS AND METHODS This phase II study followed the Simon's 2-stage optimal design. Paclitaxel (90 mg/m2) and carboplatin (2 area under the curve) were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15. The primary end point was the objective response rate (ORR). The null hypothesis that the ORR is ≤ 40% could be rejected if the number of objective responses was ≥ 23 among 46 evaluable patients. RESULTS A total of 46 patients were enrolled. Seven (15.2%) complete and 23 (50%) partial responses were observed for an ORR of 65.2% (95% confidence interval, 52.9%-80.4%). The median progression-free survival was 10.3 months, the median overall survival 25.7 months, and the median duration of response 18.2 months. Neutropenia Grade III and IV was experienced by 13 (28.3%) and 6 (13.04%) patients, respectively. One patient developed an uneventful Grade IV thrombocytopenia. There was 1 toxic death due to febrile neutropenia. Other Grade III toxicities included anemia (n = 2), neurotoxicity (n = 2), thrombocytopenia (n = 1), and diarrhea (n = 1). No serious bevacizumab-related toxicities were observed. CONCLUSION The study achieved its primary end point by showing clinical activity for weekly paclitaxel with carboplatin and bevacizumab combination. This regimen merits further evaluation in this setting.
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Affiliation(s)
- Emmanouil Saloustros
- Oncology Unit, General Hospital of Heraklion 'Venizelio-Pananio', Heraklion, Crete, Greece
| | - Michail Nikolaou
- Department of Internal Medicine, "Hippokratio" General Hospital of Athens, Athens, Greece
| | - Konstantinos Kalbakis
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Aris Polyzos
- 1st Department of Medicine, Medical School, University of Athens, Laikon General Hospital, Athens, Greece
| | | | - Nikolaos Kentepozidis
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece
| | | | | | - Lampros Vamvakas
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Vasilios Georgoulias
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Dimitris Mavroudis
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece.
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16
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Gamucci T, Pizzuti L, Sperduti I, Mentuccia L, Vaccaro A, Moscetti L, Marchetti P, Carbognin L, Michelotti A, Iezzi L, Cassano A, Grassadonia A, Astone A, Botticelli A, Magnolfi E, Di Lauro L, Sergi D, Fuso P, Tinari N, Barba M, Maugeri-Saccà M, Landucci E, Conti F, Sanguineti G, De Tursi M, Iafrate G, Giordano A, Ciliberto G, Natoli C, Vici P. Neoadjuvant chemotherapy in triple-negative breast cancer: A multicentric retrospective observational study in real-life setting. J Cell Physiol 2017; 233:2313-2323. [DOI: 10.1002/jcp.26103] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 07/14/2017] [Indexed: 02/06/2023]
Affiliation(s)
| | - Laura Pizzuti
- Division of Medical Oncology 2; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Isabella Sperduti
- IRCCS Regina Elena National Cancer Institute; Bio-Statistics Unit; Rome Italy
| | | | | | - Luca Moscetti
- Division of Medical Oncology, Department of Oncology and Hematology; University Hospital of Modena; Modena Italy
| | | | - Luisa Carbognin
- Medical Oncology, University of Verona; Azienda Ospedaliera Universitaria Integrata; Verona Italy
| | - Andrea Michelotti
- UO Oncologia Medica I, Ospedale S. Chiara, Dipartimento di oncologia, dei trapianti e delle nuove tecnologie; Azienda Ospedaliera Universitaria Pisana; Pisa Italy
| | - Laura Iezzi
- Department of Medical, Oral and Biotechnological Sciences; Centro Scienze dell'Invecchiamento e Medicina Traslazionale − CeSI-MeT; University G. D'Annunzio; Chieti Italy
| | - Alessandra Cassano
- Department of Medical Oncology; Catholic University of Sacred Heart; Rome Italy
| | - Antonino Grassadonia
- Department of Medical, Oral and Biotechnological Sciences; Centro Scienze dell'Invecchiamento e Medicina Traslazionale − CeSI-MeT; University G. D'Annunzio; Chieti Italy
| | - Antonio Astone
- Department of Medical Oncology; Catholic University of Sacred Heart; Rome Italy
| | | | | | - Luigi Di Lauro
- Division of Medical Oncology 2; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Domenico Sergi
- Division of Medical Oncology 2; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Paola Fuso
- Department of Medical Oncology; Catholic University of Sacred Heart; Rome Italy
| | - Nicola Tinari
- Department of Medical, Oral and Biotechnological Sciences; Centro Scienze dell'Invecchiamento e Medicina Traslazionale − CeSI-MeT; University G. D'Annunzio; Chieti Italy
| | - Maddalena Barba
- Division of Medical Oncology 2; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Marcello Maugeri-Saccà
- Division of Medical Oncology 2; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Elisabetta Landucci
- UO Oncologia Medica I, Ospedale S. Chiara, Dipartimento di oncologia, dei trapianti e delle nuove tecnologie; Azienda Ospedaliera Universitaria Pisana; Pisa Italy
| | - Francesca Conti
- Division of Medical Oncology 2; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Giuseppe Sanguineti
- Department of Radiotherapy; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Michele De Tursi
- Department of Medical, Oral and Biotechnological Sciences; Centro Scienze dell'Invecchiamento e Medicina Traslazionale − CeSI-MeT; University G. D'Annunzio; Chieti Italy
| | - Gianni Iafrate
- UOSD Oncologic Surgery; Ospedaletto SS Trinità; Sora Lazio Italy
| | - Antonio Giordano
- Department of Medicine, Surgery and Neuroscience; University of Siena and Istituto Toscano Tumori (ITT); Siena Italy
- Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology; Temple University; Philadelphia Pennsylvania
| | - Gennaro Ciliberto
- Scientific Direction; IRCCS Regina Elena National Cancer Institute; Rome Italy
| | - Clara Natoli
- Department of Medical, Oral and Biotechnological Sciences; Centro Scienze dell'Invecchiamento e Medicina Traslazionale − CeSI-MeT; University G. D'Annunzio; Chieti Italy
| | - Patrizia Vici
- Division of Medical Oncology 2; IRCCS Regina Elena National Cancer Institute; Rome Italy
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17
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New Insights in the Cytogenetic Practice: Karyotypic Chaos, Non-Clonal Chromosomal Alterations and Chromosomal Instability in Human Cancer and Therapy Response. Genes (Basel) 2017; 8:genes8060155. [PMID: 28587191 PMCID: PMC5485519 DOI: 10.3390/genes8060155] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Revised: 05/26/2017] [Accepted: 05/31/2017] [Indexed: 12/17/2022] Open
Abstract
Recently, non-clonal chromosomal alterations previously unappreciated are being proposed to be included in cytogenetic practice. The aim of this inclusion is to obtain a greater understanding of chromosomal instability (CIN) and tumor heterogeneity and their role in cancer evolution and therapy response. Although several genetic assays have allowed the evaluation of the variation in a population of cancer cells, these assays do not provide information at the level of individual cells, therefore limiting the information of the genomic diversity within tumors (heterogeneity). The karyotype is one of the few available cytogenetic techniques that allow us not only to identify the chromosomal alterations present within a single cell, but also allows us to profile both clonal (CCA) and non-clonal chromosomal alterations (NCCAs). A greater understanding of CIN and tumor heterogeneity in cancer could not only improve existing therapeutic regimens but could also be used as targets for the design of new therapeutic approaches. In this review we indicate the importance and significance of karyotypic chaos, NCCAs and CIN in the prognosis of human cancers.
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18
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Ding J, Yang Y, Jiang L, Wu W, Shao Z. Predictive factors of pathologic complete response in HER2-positive and axillary lymph node positive breast cancer after neoadjuvant paclitaxel, carboplatin plus with trastuzumab. Oncotarget 2017; 8:56626-56634. [PMID: 28915617 PMCID: PMC5593588 DOI: 10.18632/oncotarget.17993] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Accepted: 04/17/2017] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE This study was performed to investigate the proportion as well as the predictive factors of pathologic complete response in HER2-positive and axillary lymph node positive breast cancer after neoadjuvant paclitaxel, carboplatin plus with trastuzumab (PCH). RESULTS The pCR rate in the breast, axilla and both was 44.3% (39/88), 47.7% (42/88) and 34.1% (30/88), respectively. Patients with and without pCR were similar in term of age, BMI, menstrual status, family history, treatment cycles and tumor characteristics (laterality and size of tumor). Multivariate logistic regression demonstrated that pCR was significantly associated with HR negativity (HR = 5.587, 95% CI 2.25-3.889, p < 0.001), high Ki67 index (HR = 4.130, 95% CI 1.607-10.610, p = 0.003). Further investigation found that patients with HR-negative/high Ki67 index had higher pCR rate, compared to other patients (HR = 7.583, 95% CI 2.503-22.974, p < 0.001). MATERIALS AND METHODS 88 consecutive Chinese HER2-positive/axillary lymph node-positive breast cancer patients with neodjuvant therapy regimen containing paclitaxel, carboplatin and trastuzumab were divided into two groups: pathological complete response (pCR) or non-pCR group. Clinico-pathological characteristics were compared and analyzed, and univariate and multivariate analyses were performed to detect the predictive factors of pCR. CONCLUSIONS Preoperative PCH regimen was an effective neoadjuvant therapy in HER2 positive and axillary lymph node positive patients, and patients coexisting with HR-negative and high Ki67 index may benefit more from this regimen.
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Affiliation(s)
- Jinhua Ding
- Department of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China.,Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yinlong Yang
- Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China
| | - Li Jiang
- Department of Emergency, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China
| | - Weizhu Wu
- Department of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China
| | - Zhiming Shao
- Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China
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19
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Natori A, Ethier JL, Amir E, Cescon DW. Capecitabine in early breast cancer: A meta-analysis of randomised controlled trials. Eur J Cancer 2017; 77:40-47. [PMID: 28355581 DOI: 10.1016/j.ejca.2017.02.024] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 12/07/2016] [Accepted: 02/20/2017] [Indexed: 11/25/2022]
Abstract
PURPOSE Capecitabine is an effective therapy for metastatic breast cancer. Its role in early breast cancer is uncertain due to conflicting data from randomised controlled trials (RCTs). METHODS PubMed and major conference proceedings were searched to identify RCTs comparing standard chemotherapy with or without capecitabine in the neoadjuvant or adjuvant setting. Hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS), as well as odds ratios (ORs) for toxicities were extracted or calculated and pooled in a meta-analysis. Subgroup analysis compared triple-negative breast cancer (TNBC) to non-TNBC and whether capecitabine was given in addition to or in place of standard chemotherapy. Meta-regression was used to explore the influence of TNBC on OS. RESULTS Eight studies comprising 9302 patients were included. In unselected patients, capecitabine did not influence DFS (hazard ratio [HR] 0.99, p = 0.93) or OS (HR 0.90, p = 0.36). There was a significant difference in DFS when capecitabine was given in addition to standard treatment compared with in place of standard treatment (HR 0.92 versus 1.62, interaction p = 0.002). Addition of capecitabine to standard chemotherapy was associated with significantly improved DFS in TNBC versus non-TNBC (HR 0.72 versus 1.01, interaction p = 0.02). Meta-regression showed that adding capecitabine to standard chemotherapy was associated with improved OS in studies with higher proportions of patients with TNBC (R = -0.967, p = 0.007). Capecitabine increased grade 3/4 diarrhoea (odds ratio [OR] 2.33, p < 0.001) and hand-foot syndrome (OR 8.08, p < 0.001), and resulted in more frequent treatment discontinuation (OR 3.80, p < 0.001). CONCLUSION Adding capecitabine to standard chemotherapy appears to improve DFS and OS in TNBC, but increases adverse events in keeping with its known toxicity profile.
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Affiliation(s)
- Akina Natori
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, 200 Elizabeth Street, Suite RFE3-805, Toronto, Ontario, M5G 2C4, Canada.
| | - Josee-Lyne Ethier
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, 200 Elizabeth Street, Suite RFE3-805, Toronto, Ontario, M5G 2C4, Canada.
| | - Eitan Amir
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, 200 Elizabeth Street, Suite RFE3-805, Toronto, Ontario, M5G 2C4, Canada.
| | - David W Cescon
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, 200 Elizabeth Street, Suite RFE3-805, Toronto, Ontario, M5G 2C4, Canada.
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Kolberg HC, Akpolat-Basci L, Stephanou M, Aktas B, Hannig CV, Liedtke C. Neoadjuvant Chemotherapy with Docetaxel, Carboplatin and Weekly Trastuzumab Is Active in HER2-Positive Early Breast Cancer: Results after a Median Follow-Up of over 4 Years. Breast Care (Basel) 2016; 11:323-327. [PMID: 27920624 DOI: 10.1159/000452079] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years. Here we present 4-year follow-up data for a cohort of 78 patients treated with neoadjuvant TCH. METHODS Between 2009 and 2014 we treated 78 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) every 3 weeks (q3w) and trastuzumab (4 mg/kg loading dose then 2 mg/kg) q1w. Lymph node involvement was verified by sentinel lymph node or core-cut biopsy. Patients were diagnosed at a mean age of 55.5 years; 65.4% had hormone receptor-positive tumors, 34.6% presented with grade 3 disease and 51.3% of patients were node positive. Patients were monitored every 2 cycles by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery, trastuzumab was continued q3w up to 1 year. RESULTS No grade III/IV toxicities occurred and no case of congestive heart failure was observed. Neither dose modifications nor dose delays were necessary. 34 of the 78 patients (43.6%) achieved a pCR, 27 of the 40 node-positive patients (67.5%) experienced nodal conversion. After a median follow up of 48.5 months the disease-free survival (DFS) was 84.6%, the distant disease-free survival (DDFS) was 87.2% and the overall survival (OS) was 91%. Only T stage and nodal status at baseline were found to be significantly associated with survival estimates. CONCLUSION The anthracycline-free regimen TCH is effective and safe in the neoadjuvant therapy of HER2-positive breast cancer, yielding DFS, DDFS and OS probabilities comparable to the results of adjuvant trials. Our data support the use of TCH as a neoadjuvant therapy regimen for patients with HER2-positive breast cancer. They also strongly encourage the use of taxanes and platinum salts as the chemotherapy backbone in studies investigating dual blockade with trastuzumab and pertuzumab in the neoadjuvant setting.
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Affiliation(s)
- Hans-Christian Kolberg
- Klinik für Gynäkologie und Geburtshilfe, Marienhospital Bottrop, Bottrop, Germany, Lübeck, Germany
| | - Leyla Akpolat-Basci
- Klinik für Gynäkologie und Geburtshilfe, Marienhospital Bottrop, Bottrop, Germany, Lübeck, Germany
| | - Miltiades Stephanou
- Klinik für Gynäkologie und Geburtshilfe, Marienhospital Bottrop, Bottrop, Germany, Lübeck, Germany
| | - Bahriye Aktas
- Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Essen, Essen, Germany, Lübeck, Germany
| | - Carla Verena Hannig
- Schwerpunktpraxis für Hämatologie und Onkologie, Bottrop, Germany, Lübeck, Germany
| | - Cornelia Liedtke
- Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein Campus Lübeck, Lübeck, Germany
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Dębska-Szmich S, Krakowska M, Czernek U, Habib-Lisik M, Zięba A, Potemski P. The role of preoperative systemic treatment in patients with breast cancer. Contemp Oncol (Pozn) 2016; 20:93-101. [PMID: 27358586 PMCID: PMC4925732 DOI: 10.5114/wo.2016.60067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Accepted: 05/29/2014] [Indexed: 12/31/2022] Open
Abstract
The goal of preoperative pharmacotherapy in patients with breast cancer is to enable breast conserving surgery in stage T3N0-1M0 or radical mastectomy in patients with primary inoperative tumors (T1-4N0-3M0). The choice of optimal treatment should be based not only on risk factors resulting from the stage but also on predicted cancer responsiveness to the treatment. The breast cancer subtypes defined by immunohistochemical profile (expression of ER, PR, HER2 and Ki67) are characterized by different responsiveness to therapy. Complete response confirmed by histopathological evaluation after neoadjuvant chemotherapy is a positive prognostic factor in some breast cancer subtypes. This marker is not of value in postmenopausal patients with ER/PR+ HER2- tumors, who are candidates for neoadjuvant hormone therapy. These patients have a good prognosis if in a histopathological report after surgery there are features such as pT1, pN0, Ki67 < 3%, and ER Allred score ≥ 3. The goal of the paper is to present current knowledge about preoperative pharmacotherapy of breast cancer.
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Affiliation(s)
- Sylwia Dębska-Szmich
- Department of Chemotherapy, Chair of Oncology, Medical University of Lodz, Poland
| | - Magdalena Krakowska
- Department of Chemotherapy, Chair of Oncology, Medical University of Lodz, Poland
| | - Urszula Czernek
- Department of Chemotherapy, Chair of Oncology, Medical University of Lodz, Poland
| | - Maja Habib-Lisik
- Department of Chemotherapy, Chair of Oncology, Medical University of Lodz, Poland
| | - Agnieszka Zięba
- Department of Chemotherapy, Chair of Oncology, Medical University of Lodz, Poland
| | - Piotr Potemski
- Department of Chemotherapy, Chair of Oncology, Medical University of Lodz, Poland
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Wasserman JK, Williams PA, Islam S, Robertson SJ. GATA-3 expression is not associated with complete pathological response in triple negative breast cancer patients treated with neoadjuvant chemotherapy. Pathol Res Pract 2016; 212:539-44. [DOI: 10.1016/j.prp.2016.03.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 02/08/2016] [Accepted: 03/15/2016] [Indexed: 11/26/2022]
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A phase II trial of dose-dense (biweekly) paclitaxel plus carboplatin as neoadjuvant chemotherapy for operable breast cancer. Breast Cancer Res Treat 2016; 156:117-24. [PMID: 26936755 DOI: 10.1007/s10549-016-3735-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 02/25/2016] [Indexed: 10/22/2022]
Abstract
The aim of the present study is to investigate the efficacy and safety of dose-dense (biweekly) carboplatin and paclitaxel as a neoadjuvant treatment for operable breast cancer. Patients with previously untreated breast cancer (stages Ic-III) were treated with four cycles of paclitaxel (175 mg/m(2), intravenous drip, D1) and carboplatin (area under the curve of 5, D1). Patients with HER2+ disease simultaneously received trastuzumab (6 mg/kg initial dose with subsequent doses of 4 mg/kg biweekly). The primary endpoint was a pathologically complete response (pCR). Between January 2012 and February 2014, 110 patients were enrolled. The overall pCR rate was 35.45 % (39 of 110). The pCR rates for the different cancer subtypes were as follows: 10.53 % (2 of 19) among the patients with the luminal A subtype, 12.50 % (5 of 40) among the patients with the luminal B (HER2-) subtype, 58.33 % (14 of 24) among the patients with the luminal B (HER2+) subtype, 57.14 % (8 of 14) among the patients with the triple-negative subtype, and 76.92 % (10 of 13) among the patients with the HER2+ subtype. The patients experienced the following toxicity side effects: grade 3/4 neutropenia (N = 27, 24.55 %), grade 3/4 anemia (N = 6, 5.45 %), grade 3/4 thrombocytopenia (N = 2, 1.82 %), grade 3 alanine aminotransferase (ALT) elevation (N = 1, 0.91 %), grade 3 neuropathy (N = 3, 2.73 %), grade 3 pain (N = 2, 1.82 %), and grade 3 fatigue (N = 1, 0.91 %). In total, 19.09 % of the patients experienced treatment delay or discontinuation due to hematological toxicity, and one patient discontinued treatment due to non-hematological toxicity. Neoadjuvant biweekly paclitaxel plus carboplatin is a feasible therapy that achieved high pCR rates in patients with the HER2+, triple-negative, and luminal B (HER2+) cancer subtypes (NCT0205986).
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Okamoto S, Yamada T, Kanemaki Y, Kojima Y, Tsugawa K, Nakajima Y. Magnetic resonance examination to predict pathological complete response following neoadjuvant chemotherapy: when is it appropriate for HER2-positive and triple-negative breast cancers? Breast Cancer 2015; 23:789-96. [PMID: 26437647 DOI: 10.1007/s12282-015-0642-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 09/23/2015] [Indexed: 11/26/2022]
Abstract
BACKGROUND To clarify appropriate timing for magnetic resonance examination to predict pathological complete response to neoadjuvant chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers in terms of tumor volume change. METHODS Between September 2009 and December 2014, 113 women with HER2-positive (n = 51) and triple-negative (n = 62) invasive breast cancers undergoing neoadjuvant chemotherapy were enrolled. Patients with HER2-positive tumors underwent neoadjuvant chemotherapy with an anthracycline-based regimen followed by docetaxel with trastuzumab. Patients with triple-negative tumors underwent neoadjuvant chemotherapy with anthracycline-based (first in most cases) and taxane-based regimens. Magnetic resonance imaging was performed before neoadjuvant chemotherapy, between the regimens (midpoint examination), and after neoadjuvant chemotherapy (final examination). Response ratio of tumor volume was calculated and receiver-operating characteristic analyses for them for both subtypes were performed at the midpoint and final examinations. RESULTS Twenty-eight women with HER2-positive tumors (54.9 %) and 29 women with triple-negative tumors (46.8 %) had pathological complete response. The response ratios were better in cases with pathological complete response than in those without (p = 0.0341, p < 0.0001). The area under the curve at the final examination was higher than that at the midpoint examination for HER2-positive tumors (p = 0.039); whereas for the triple-negative tumors, no significant difference between the two examinations was shown (p = 0.5218). CONCLUSIONS Magnetic resonance examination to predict pathological complete response would be feasible after completion of a regimen including trastuzumab for HER2-positive tumors and at the midpoint of neoadjuvant chemotherapy for triple-negative tumors.
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Affiliation(s)
- Satoko Okamoto
- Department of Radiology, Breast and Imaging Center, St. Marianna University School of Medicine, 6-7-2 Manpukuji, Asao-ku, Kawasaki, Kanagawa, 215-0004, Japan.
| | - Takayuki Yamada
- Department of Radiology, Yokohama City Seibu Hospital, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Yoshihide Kanemaki
- Department of Radiology, Breast and Imaging Center, St. Marianna University School of Medicine, 6-7-2 Manpukuji, Asao-ku, Kawasaki, Kanagawa, 215-0004, Japan
| | - Yasuyuki Kojima
- Department of Breast Surgical Oncology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Koichiro Tsugawa
- Department of Breast Surgical Oncology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Yasuo Nakajima
- Department of Radiology, St. Marianna University School of Medicine, Kanagawa, Japan
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Abstract
As anticipated by their structure and mechanism of action, platinum analogs exhibit clinically significant antitumor activity in the more aggressive forms of breast cancer, both alone and in combination with other cytotoxic agents and targeted therapies. In early-stage human epidermal growth factor receptor-2 (HER2)-positive breast cancer, the administration of carboplatin together with a taxane (usually docetaxel) and trastuzumab (and pertuzumab in the neoadjuvant setting) is a standard of care regimen. In BRCA1 mutation carriers, neoadjuvant treatment with single-agent cisplatin results in a high pathologic complete response (pCR) rate. In both BRCA-mutated and sporadic triple-negative breast cancer, the addition of carboplatin to neoadjuvant chemotherapy significantly increases pCR rates. Despite these encouraging results, many questions remain about the role of platinum analogs in these patient populations, including their optimal doses and schedules, and utility in patients with advanced stage disease. A number of these questions are addressed by ongoing trials.
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Affiliation(s)
- William M Sikov
- Women and Infants Hospital, Breast Health Center, 101 Dudley Street, Providence, RI, 02905, USA,
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Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstet 2015; 293:247-69. [PMID: 26341644 DOI: 10.1007/s00404-015-3859-y] [Citation(s) in RCA: 474] [Impact Index Per Article: 47.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Accepted: 08/18/2015] [Indexed: 12/22/2022]
Abstract
PURPOSE Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors comprising various breast cancers simply defined by the absence of estrogen receptor, progesterone receptor and overexpression of human epidermal growth factor receptor 2 gene. In this review, we discuss the epidemiology, risk factors, clinical characteristics and prognostic variables of TNBC, and present the summary of recommended treatment strategies and all other available treatment options. METHODS We performed a systematic literature search using Medline and selected those articles which seemed relevant for this review. In addition, the ClinicalTrials.gov was also scanned for ongoing trials. RESULTS TNBC accounts for 10-20 % of all invasive breast cancers and has been found to be associated with African-American race, younger age, higher grade and mitotic index, and more advanced stage at diagnosis. Locoregional treatment is similar to other invasive breast cancer subtypes and involves surgery-mastectomy with or without adjuvant radiotherapy or breast conservation followed by adjuvant radiotherapy. Due to lack of drug-targetable receptors, chemotherapy is the only recommended systemic treatment to improve disease outcome. TNBC is sensitive to chemotherapy as demonstrated by high pathological complete response rates achieved after neoadjuvant chemotherapy, and this approach also allows for breast-conserving surgery. The peak risk of relapse is at 3 years after surgery, thereafter recurrence risk rapidly decreases. Survival after metastatic relapse is shorter as compared to other breast cancer subtypes, treatment options are few and response rates are poor and lack durability. Important molecular characteristics have now been identified that can subdivide this group of breast cancers further and can provide alternative systemic therapies. CONCLUSIONS To improve therapeutic outcome of TNBC, reliable predictive biomarkers and newer drugs against the known molecular pathways are required.
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Affiliation(s)
- Pankaj Kumar
- Department of Radiation Oncology, Max Super Speciality Hospital, Phase-6, Mohali, 160055, Punjab, India.
| | - Rupali Aggarwal
- Department of Radiation Oncology, Indus Super Speciality Hospital, Phase-1, Mohali, 160055, Punjab, India
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Abstract
PURPOSE OF REVIEW Although patients with hormone receptor-positive and/or HER2-positive breast cancer benefit from endocrine and HER2-targeted agents in addition to combination chemotherapy regimens, patients with triple-negative breast cancer (TNBC) suffer from a particularly unfavorable prognosis particularly when not responding well to anthracycline-taxane chemotherapy. Novel treatment options are urgently needed to improve prognosis of these patients as well. RECENT FINDINGS Potential options for optimized therapy of patients with TNBC consist in, first, optimization of chemotherapy through optimization of chemotherapy regimens with may be reached through optimized (i.e., dose-dense) scheduling, second, optimization of chemotherapy through introduction of novel chemotherapy agents (such as platinum compounds as alternative of additional chemotherapy), third, identification and development of novel targeted agents, and fourth, identification of patients with or without response through biomarkers to individual treatments to allow for a more personalized treatment approach. SUMMARY We summarize recent findings for novel treatment options particularly focusing on platinum-based chemotherapy, potential novel targeted therapies such as antiangiogenic agents or inhibition of poly-A-ribose-polymerase, and prognostic/predictive biomarkers such as tumor-infiltrating lymphocytes or BRCA.
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Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement. Rev Esp Med Nucl Imagen Mol 2015. [DOI: 10.1016/j.remnie.2015.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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[Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement]. Rev Esp Med Nucl Imagen Mol 2015; 34:230-5. [PMID: 25743035 DOI: 10.1016/j.remn.2015.01.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 01/19/2015] [Accepted: 01/21/2015] [Indexed: 11/20/2022]
Abstract
AIM To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). MATERIAL AND METHODS Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. RESULTS A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. CONCLUSION More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy.
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Shinde AM, Zhai J, Yu KW, Frankel P, Yim JH, Luu T, Kruper L, Vito C, Shaw S, Vora NL, Kirschenbaum M, Somlo G. Pathologic complete response rates in triple-negative, HER2-positive, and hormone receptor-positive breast cancers after anthracycline-free neoadjuvant chemotherapy with carboplatin and paclitaxel with or without trastuzumab. Breast 2015; 24:18-23. [PMID: 25467313 PMCID: PMC4596816 DOI: 10.1016/j.breast.2014.10.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Revised: 10/11/2014] [Accepted: 10/24/2014] [Indexed: 10/24/2022] Open
Abstract
BACKGROUND Pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) is considered a surrogate for improved survival. Platinum-containing NCT, particularly in patients with HER2+ and triple-negative breast cancers (TNBC) may increase pCR rates. METHODS Tumor characteristics, pCR rates (no invasive disease in breast and lymph nodes), toxicities, and survival in patients who received carboplatin, a taxane, and trastuzumab (HER2+ disease) between April 2009 and December 2011, were reviewed. RESULTS Thirty eight patients (39 tumors) completed a median of 4 cycles of NCT. Eighteen of 39 (46%) tumors were HER2+, 8/18 (44%) responded with pCR; 13/18 HER2+ tumors were HR+ (72%) and 4/13 (31%) had a pCR. Ten of 39 (26%) tumors were TNBC; 6/10 (60%) had a pCR. At a median of 25-months no recurrences were observed in patients with pCR. CONCLUSIONS Prospective studies of anthracycline-free platinum-containing NCT are warranted in LABC patients with HER2+ and TNBC.
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Affiliation(s)
- Arvind M Shinde
- Department of Medical Oncology and Therapeutic Research, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - Jing Zhai
- Department of Pathology, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - Kim Wai Yu
- Department of Clinical Pharmacy, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - Paul Frankel
- Department of Information Sciences, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - John H Yim
- Department of General Oncologic Surgery, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - Thehang Luu
- Department of Medical Oncology and Therapeutic Research, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - Laura Kruper
- Department of General Oncologic Surgery, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - Courtney Vito
- Department of General Oncologic Surgery, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - Sally Shaw
- Department of Diagnostic Radiology, City of Hope, 1500 East Duarte Rd., Duarte, CA, 91010 USA
| | - Nayana L Vora
- Department of Diagnostic Radiology, City of Hope, 1500 East Duarte Rd., Duarte, CA, 91010 USA
| | - Michele Kirschenbaum
- Office of Clinical Trials, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA
| | - George Somlo
- Department of Medical Oncology and Therapeutic Research, City of Hope, 1500 East Duarte Rd., Duarte, CA 91010, USA.
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Gogia A, Raina V, Deo SV, Shukla NK, Mohanti BK, Sharma DN. Taxane and anthracycline based neoadjuvant chemotherapy for locally advanced breast cancer: institutional experience. Asian Pac J Cancer Prev 2014; 15:1989-92. [PMID: 24716923 DOI: 10.7314/apjcp.2014.15.5.1989] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The aim of this study was to assess the response rates (clinical and pathological ) with docetaxel and epirubicin combination chemotherapy and its effect on outcome. MATERIALS AND METHODS We retrospectively analysed locally advanced breast cancer (LABC) patients who received NACT from January 2008 to December 2012 in our tertiary care centre. LABC constituted 37% of all breast cancer cases and 120 patients fulfilled the eligibility criteria. The regimens used for NACT were, six cycles of DEC (docetaxel 75 mg/m2, epirubicin 75 mg/ m2, cyclophosphamide 500 mg/m2 on Day 1, 3 weekly) and a sequential regimen (4 cycles of FEC, 5-flurouracil 600 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2 followed by 4 cycles of docetaxel 85 mg/m2). RESULTS The median age was 47 years (range 23-72). Ninety six ( 80 %) had T4 disease and 90% had clinically palpable lymph nodes at diagnosis. The median size of primary tumor at presentation was 5.9 cm. Hormone receptor positivity was seen in 55% and HER2/neu positivity, in 25%. Triple negative breast cancers constituted 25 % of the cases. The overall clinical response rate ( complete or partial ) was 85% and pathological complete responses were obtained in 15%. Four cases defaulted, 5 patients died of treatment related toxicity and 15% developed febrile neutropenia on DEC. The median duration of follow up was 22 months. The median time to relapse was 20 months and the 3 year relapse free and overall survival rates were 50% and 70% respectively. CONCLUSIONS LABC constituted 37% of all breast cancer cases at our institute. With NACT, pCR was seen in 15% of the cases. Sequential chemotherapy was better tolerated than concurrent anthracyline and taxane chemotherapy with a similar pCR.
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Affiliation(s)
- Ajay Gogia
- Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India E-mail :
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Abstract
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.
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Affiliation(s)
- Jennifer Lee
- Dr. Lee is a pharmacist at Mirixa Corporation, Reston, Virginia. At the time this article was written, she was a student at the University of Maryland, School of Pharmacy , Baltimore, Maryland
| | - Dominic A Solimando
- Dr. Lee is a pharmacist at Mirixa Corporation, Reston, Virginia. At the time this article was written, she was a student at the University of Maryland, School of Pharmacy , Baltimore, Maryland
| | - J Aubrey Waddell
- Dr. Lee is a pharmacist at Mirixa Corporation, Reston, Virginia. At the time this article was written, she was a student at the University of Maryland, School of Pharmacy , Baltimore, Maryland
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Clinical Evaluation of Platinum Agents for the Treatment of Triple Negative Breast Cancer. CURRENT BREAST CANCER REPORTS 2014. [DOI: 10.1007/s12609-014-0160-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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The efficacy and safety of preoperative chemotherapy with triweekly abraxane and cyclophosphamide followed by 5-Fluorouracil, epirubicin, and cyclophosphamide therapy for resectable breast cancer: a multicenter clinical trial. Clin Breast Cancer 2014; 15:110-6. [PMID: 25454688 DOI: 10.1016/j.clbc.2014.09.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 09/25/2014] [Indexed: 11/21/2022]
Abstract
BACKGROUND It has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy, and that cyclophosphamide combined with taxane shows an enhanced antitumor effect. We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC. PATIENTS AND METHODS From September 2011 to September 2013, 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer. In patients with HER2-positive breast cancer, tri-weekly Trastuzumab was administered with TRI-ABC. The primary end point was the pathological complete response (pCR) rate in the breasts and lymph nodes. RESULTS The treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy. All patients underwent radical surgery, and the overall pCR rate of 37% (20 of 54) was achieved. The pCR rates according to each subtype were 8% (2 of 24) in hormone receptor (HR)-positive HER2-negative breast cancer, 56% (5 of 9) in HR-positive HER2-positive breast cancer, 63% (5 of 8) in HR-negative HER2-positive breast cancer, and 62% (8 of 13) in triple-negative breast cancer. Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR. Clinical response was observed in 49 patients (91%). The safety profile was acceptable. CONCLUSION Preoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety. Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane-anthracycline regimens.
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Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol 2014; 33:13-21. [PMID: 25092775 DOI: 10.1200/jco.2014.57.0572] [Citation(s) in RCA: 706] [Impact Index Per Article: 64.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
PURPOSE One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. PATIENTS AND METHODS Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m(2) once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. RESULTS Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. CONCLUSION In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.
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Affiliation(s)
- William M Sikov
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL.
| | - Donald A Berry
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Charles M Perou
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Baljit Singh
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Constance T Cirrincione
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Sara M Tolaney
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Charles S Kuzma
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Timothy J Pluard
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - George Somlo
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Elisa R Port
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Mehra Golshan
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Jennifer R Bellon
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Deborah Collyar
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Olwen M Hahn
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Lisa A Carey
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Clifford A Hudis
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
| | - Eric P Winer
- William M. Sikov, Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; Donald A. Berry, University of Texas MD Anderson Cancer Center, Houston, TX; Charles M. Perou and Lisa A. Carey, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill; Constance T. Cirrincione, Alliance Statistical Center, Durham; Charles S. Kuzma, Southeast Cancer Control Consortium, Winston-Salem, NC; Baljit Singh, New York University Medical Center; Elisa R. Port, Mount Sinai Medical Center; Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Sara M. Tolaney, Mehra Golshan, Jennifer R. Bellon, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Timothy J. Pluard, Washington University-St Louis Medical Center, St Louis, MO; George Somlo, City of Hope Comprehensive Cancer Center, Duarte; Deborah Collyar, Patient Advocates in Research, Danville, CA; and Olwen M. Hahn, University of Chicago Medical Center, Chicago, IL
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Yadav BS, Sharma SC, Chanana P, Jhamb S. Systemic treatment strategies for triple-negative breast cancer. World J Clin Oncol 2014; 5:125-133. [PMID: 24829859 PMCID: PMC4014784 DOI: 10.5306/wjco.v5.i2.125] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Revised: 12/25/2013] [Accepted: 01/17/2014] [Indexed: 02/06/2023] Open
Abstract
Triple-negative breast cancer (TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2 (EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival (PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitors in combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.
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Cardiotoxicity of systemic agents used in breast cancer. Breast 2014; 23:317-28. [PMID: 24794210 DOI: 10.1016/j.breast.2014.04.002] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Revised: 03/21/2014] [Accepted: 04/03/2014] [Indexed: 11/21/2022] Open
Abstract
Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines can cause permanent damage, anti-HER2 agents may cause transitory and reversible cardiac dysfunction and others, such as those used in endocrine therapy, primarily disturb lipid metabolism. Considering the seriousness of these complications, trials are now being conducted to address cardiotoxicity associated with new drugs; however, to fully understand their toxicity profiles, longer follow-up is needed. In this review, we compile the information available about cardiac toxicity related to well-established systemic breast cancer treatments, as well as newer drugs, including antiangiogenics, mTOR inhibitors and novel anti-HER2 agents. We also describe current and next generation cardiac biomarkers and functional tests that can optimize treatment and reduce and prevent the incidence of treatment-related cardiotoxicity.
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Wu K, Yang Q, Liu Y, Wu A, Yang Z. Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy. World J Surg Oncol 2014; 12:95. [PMID: 24731479 PMCID: PMC4011773 DOI: 10.1186/1477-7819-12-95] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2014] [Accepted: 04/04/2014] [Indexed: 12/31/2022] Open
Abstract
Background Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that is characterized by poor prognosis, strong tumor invasion and a high pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). The pCR rate is a prognostic factor for TNBC. We aimed to evaluate the relationship between pCR and TNBC after NAC and originally tried to identify factors related to achieving pCR for TNBC using a meta-analysis. Methods We systematically searched the literature for pCR and breast cancer after NAC and carefully identified eligibility criteria. The association between pCR and breast cancer subtypes was estimated using Review Manager, while pCR rates for TNBC and non-TNBC were determined using Meta-Analyst. Results This analysis included a total of 9,460 cases from 27 studies. The summary odds ratio estimating the relationship between pCR and breast cancer subtypes (TNBC vs non-TNBC) was 3.02 (95% confidence interval (CI), 2.66 to 3.42). The TNBC pCR rate was 28.9% (95% CI, 27.0 to 30.8%) and the non-TNBC was 12.5% (95% CI, 11.7 to 13.4%). From subgroup analyses, we identified the factors associated with the highest pCR rates for TNBC. Conclusions TNBC has a higher pCR rate than non-TNBC. In the NAC setting, these factors of platinum-containing, more than six cycles, four kinds of drugs, 16 weeks’ treatment duration and sequential chemotherapy may contribute to increasing the pCR rate.
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Affiliation(s)
| | | | | | - Aibing Wu
- Cancer Center, Affiliated Hospital of Guangdong Medical College, 57 Renmin Road, Zhanjiang, PR China.
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Ratanaphan A, Canyuk B. Host Cell Reactivation and Transcriptional Activation of Carboplatin-Modified BRCA1. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2014; 8:51-6. [PMID: 24678242 PMCID: PMC3964185 DOI: 10.4137/bcbcr.s14224] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Revised: 01/29/2014] [Accepted: 02/05/2014] [Indexed: 12/13/2022]
Abstract
The breast cancer susceptibility gene 1 (BRCA1) has been shown to maintain genomic stability through multiple functions in the regulation of DNA damage repair and transcription. Its translated BRCT (BRCA1 C-terminal domain) acts as a strong transcriptional activator. BRCA1 damaged by carboplatin treatment may lead to a loss of such functions. To address the possibility of the BRCA1 gene as a therapeutic target for carboplatin, we investigated the functional consequences of the 3′-terminal region of human BRCA1 following in vitro platination with carboplatin. A reduction in cellular BRCA1 repair of carboplatin-treated plasmid DNA, using a host cell reactivation assay, was dependent on the platination levels on the reporter gene. The transcriptional transactivation activity of the drug-modified BRCA1, assessed using a one-hybrid GAL4 transcriptional assay, was inversely proportional to the carboplatin doses. The data emphasized the potential of the BRCA1 gene to be a target for carboplatin treatment.
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Affiliation(s)
- Adisorn Ratanaphan
- Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla, Thailand
| | - Bhutorn Canyuk
- Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla, Thailand
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Petrelli F, Coinu A, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, Barni S. The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 2014; 144:223-32. [PMID: 24557340 DOI: 10.1007/s10549-014-2876-z] [Citation(s) in RCA: 105] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2014] [Accepted: 02/07/2014] [Indexed: 11/27/2022]
Abstract
Platinum agents such as cisplatin and carboplatin are DNA-damaging agents with activity in breast cancer (BC), particularly in the triple negative (TN) subgroup. The utility of platinum agents, in addition to standard neoadjuvant chemotherapy (NAC), is controversial. To assess the activity of platinum agents in patients with TNBC treated with NAC, we performed a systematic review and meta-analysis of all published studies. A search of PubMed, EMBASE, the Web of Science, SCOPUS, and the Cochrane Central Register of Controlled Trials was performed to identify studies that investigated platinum-based NAC in patients with TNBC. Random effect models were adopted to estimate the summary risk ratio (RR), and the publication bias was evaluated using a funnel plot and Egger's regression asymmetry test. The primary endpoints were the pooled rate of the pathologic complete response (pCR) and the RR to obtain a pCR in patients treated versus not treated with NAC containing platinum agents. 28 studies were included (six randomized controlled trials and 22 retrospective or prospective studies) for a total of 1,598 TNBC patients. Overall, the pooled rate of pCR in patients treated with platinum-based NAC was 45 %. In randomized trials, NAC containing cisplatin or carboplatin significantly increased the rate of pCR compared with nonplatinum agents (RR = 1.45, 95 % CI 1.25-1.68; P < 0.0001). Compared with non-TN, TNBCs were associated with a threefold increase in the pCR rate when treated with platinum-based NAC (RR 3.32, 95 % CI 2.39-4.61; P < 0.0001). In conclusion, pCR rates increase significantly with the addition of cisplatin or carboplatin in TNBC compared with NAC containing no platinum drugs. TN status is a predictor of benefit from platinum-based NAC.
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Affiliation(s)
- Fausto Petrelli
- Division of Medical Oncology, Department of Medical Oncology, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy,
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Mrózek E, Layman R, Ramaswamy B, Lustberg M, Vecchione A, Knopp MV, Shapiro CL. Phase II trial of neoadjuvant weekly nanoparticle albumin-bound paclitaxel, carboplatin, and biweekly bevacizumab therapy in women with clinical stage II or III HER2-negative breast cancer. Clin Breast Cancer 2014; 14:228-34. [PMID: 24703985 DOI: 10.1016/j.clbc.2014.02.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2014] [Accepted: 02/12/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND We hypothesized that adding bevacizumab to neoadjuvant chemotherapy (NCT) with nab-P and carboplatin would increase the rates of pCR in BC patients and that early changes in tumor vascularity imaged by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) would predict pCR. METHODS Thirty-three women with clinical stage II or III HER2-negative BC received nab-P 100 mg/m2 and carboplatin area under the curve = 2 on days 1, 8, and 15 in combination with bevacizumab 10 mg/kg on days 1 and 15 administered every 28 days. RESULTS Six patients (18%) achieved pCR, all pCRs occurred in triple-negative BC (TNBC) (pCR = 50% for TNBC). At the end of cycle 2, the changes in relative angiogenic volume were significantly different between responders and nonresponders (P = .001). The major toxicity of this NCT was myelosuppression. CONCLUSION NCT with weekly nab-P, carboplatin, and biweekly bevacizumab resulted in a pCR rate that was neither superior to the historical data with anthracycline- or taxane-containing NCT nor to carboplatin and taxane combinations in patients with HER2-negative BC. In patients with TNBC, the observed pCR rate was 50%. The early changes in the relative angiogenic volume imaged by DCE-MRI could predict pCR.
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Affiliation(s)
- Ewa Mrózek
- Division of Medical Oncology, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH.
| | - Rachel Layman
- Division of Medical Oncology, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
| | - Bhuvaneswari Ramaswamy
- Division of Medical Oncology, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
| | - Maryam Lustberg
- Division of Medical Oncology, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
| | - Andrea Vecchione
- Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Michael V Knopp
- Division of Imaging Science, Department of Radiology, The Ohio State University, Columbus, OH
| | - Charles L Shapiro
- Division of Medical Oncology, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
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Khasraw M, Bell R. Primary systemic therapy in HER2-amplified breast cancer: a clinical review. Expert Rev Anticancer Ther 2014; 12:1005-13. [DOI: 10.1586/era.12.62] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Bardia A, Baselga J. Neoadjuvant therapy as a platform for drug development and approval in breast cancer. Clin Cancer Res 2013; 19:6360-70. [PMID: 24298066 DOI: 10.1158/1078-0432.ccr-13-0916] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The traditional drug development process in breast cancer based on large phase III studies has serious limitations and needs a major overhaul. Searching for new approaches, the testing of novel agents in the preoperative (neoadjuvant) setting approach offers a potentially rapid and efficient strategy for drug development utilizing pathologic complete response (path CR), a surrogate marker for survival, as the primary endpoint. In addition, neoadjuvant studies allow the assessment of drug effects on the target (pharmacodynamic response) and the development of predictive biomarkers of response. Molecular profiling of the residual tumor in the surgical specimen may also provide insights into actionable mechanisms of resistance. Recognizing the potential of neoadjuvant trials for drug development, the U.S. Food and Drug Administration (FDA) recently announced consideration of neoadjuvant trials for accelerated drug approval in early breast cancer, particularly for tumors with high risk of recurrence and unfavorable prognosis, and provided accelerated approval to neoadjuvant pertuzumab in September 2013. The FDA has emphasized that while improvement in path CR could be utilized for "accelerated" approval, improvement in survival will still need to be demonstrated for "regular" approval. Key considerations in conduct of such neoadjuvant drug development trials include (i) study design such as utilization of biomarker stratified design to evaluate a biomarker that could enrich response, (ii) definition of path CR, (iii) distribution of factors that influence path CR between the treatment arms, (iv) prespecified plan for follow-up to obtain data on survival, and (v) safety as it involves a patient population with curable disease. In the years to come, we anticipate an increase in the number of neoadjuvant trials testing novel therapies that hopefully will open a new path in bringing efficacious new therapies to patients with breast cancer.
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Affiliation(s)
- Aditya Bardia
- Authors' Affiliations: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; and Memorial Sloan-Kettering Cancer Center, New York, New York
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44
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Dual Targeting of Human Epidermal Growth Factor Receptor 2 (HER2) in Neoadjuvant Trials for Operable HER2 Positive (HER2+) Disease. CURRENT BREAST CANCER REPORTS 2013. [DOI: 10.1007/s12609-013-0124-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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45
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Triple-negative breast cancer possibly transforming into malignant melanoma due to targeted therapy? A case report and review of literature. Wien Med Wochenschr 2013; 163:495-8. [PMID: 24221053 DOI: 10.1007/s10354-013-0242-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 09/22/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND Triple-negative breast cancer (TNBC) is characterized by lacking expression of estrogen receptor and progesterone receptor as well as absence of human epidermal growth factor receptor 2 overexpression and is an aggressive clinical phenotype. PATIENTS AND METHODS We report the case of a 33-year-old woman who has been treated using a targeted approach for TNBC and developed a malignant melanoma metastasis without any primary. RESULTS AND CONCLUSION Using targeted therapies, tumors can be treated much more effectively, but up to now, we do not know much about potential adverse reactions. Due to the targeted therapy, tumors may be pressurized for transformation. We call for further investigations to rule out the potential risks of targeted therapy in TNBC. This is the first report of a potential transforming of one tumor entity to another by a targeted therapy.
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Bozza C, Osa EO, Puglisi F. Primary therapy in breast cancer: what have we learned from landmark trials? WOMENS HEALTH 2013; 9:583-93. [PMID: 24161310 DOI: 10.2217/whe.13.55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Primary anticancer therapy is currently accepted as a therapeutic option for patients with early-stage breast cancer. Its objectives are to increase the chance of achieving a conservative surgery and, similar to adjuvant chemotherapy, to reduce the risk of distant recurrence. The prognostic significance of obtaining a pathological complete response has been evaluated in several randomized clinical trials and meta-analyses. Growing evidence suggests that pathological complete response may act as a valid predictor of overall survival. Of note, a significant association between pathological complete response and outcome has especially been observed in patients with HER2-positive and triple-negative (hormonal receptors negative and HER2-negative) breast cancer. This review focuses on recent trials of neoadjuvant treatment with specific attention to HER2-negative disease.
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Affiliation(s)
- Claudia Bozza
- Department of Oncology, University Hospital of Udine, Udine, Italy
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Connolly R, Stearns V. Current approaches for neoadjuvant chemotherapy in breast cancer. Eur J Pharmacol 2013; 717:58-66. [PMID: 23545358 PMCID: PMC3758450 DOI: 10.1016/j.ejphar.2013.02.057] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2012] [Revised: 02/01/2013] [Accepted: 02/05/2013] [Indexed: 10/27/2022]
Abstract
Compared to adjuvant chemotherapy, the administration of the same regimen in the neoadjuvant setting provides women with identical improvements in disease free and overall survival. Neoadjuvant chemotherapy may offer benefits to properly selected women such as broadening surgical options and enhancing the likelihood of breast conservation. Assessment of response to neoadjuvant chemotherapy provides women with an individualized estimate of prognosis. For example, a woman who achieves a complete pathological response following neoadjuvant chemotherapy has a very low risk of recurrence compared to a woman with similar tumor characteristics and a large residual disease. In this review we will provide a historical perspective and discuss the aims of neoadjuvant chemotherapy in primary operable breast cancer; as well as appropriate patient selection, treatment strategies, response monitoring, and postoperative care. We will also discuss the attractiveness of this approach to study the mechanism of action of standard and novel agents, and the role of predictive biomarkers of response to treatment and outcomes.
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Affiliation(s)
- Roisin Connolly
- Assistant Professor of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans Street, CRB I, Room 153, Baltimore, MD 21287-0013, Phone 410-614-9217, Fax 410-614-4073,
| | - Vered Stearns
- Associate Professor of Oncology, Breast Cancer Research Chair in Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans Street, CRB I, Room 145, Baltimore, MD 21287-0013, Phone 443-287-6489, Fax 410-955-0125,
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48
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Engebraaten O, Vollan HKM, Børresen-Dale AL. Triple-negative breast cancer and the need for new therapeutic targets. THE AMERICAN JOURNAL OF PATHOLOGY 2013; 183:1064-1074. [PMID: 23920327 DOI: 10.1016/j.ajpath.2013.05.033] [Citation(s) in RCA: 121] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Revised: 05/22/2013] [Accepted: 05/28/2013] [Indexed: 12/17/2022]
Abstract
Triple-negative breast cancers (TNBCs) are a diverse and heterogeneous group of tumors that by definition lack estrogen and progesterone receptors and amplification of the HER2 gene. The majority of the tumors classified as TNBCs are highly malignant, and only a subgroup responds to conventional chemotherapy with a favorable prognosis. Results from decades of research have identified important molecular characteristics that can subdivide this group of breast cancers further. High-throughput molecular analyses including sequencing, pathway analyses, and integrated analyses of alterations at the genomic and transcriptomic levels have improved our understanding of the molecular alterations involved in tumor development and progression. How this knowledge should be used for rational selection of therapy is a challenging task and the subject of numerous ongoing research programs. This review summarizes the current knowledge on the clinical characteristics and molecular alterations of TNBCs. Currently used conventional therapeutic strategies and targeted therapy studies are discussed, with references to recently published results on the molecular characterization of TNBCs.
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Affiliation(s)
- Olav Engebraaten
- Division of Cancer Medicine, Surgery and Transplantation, Department of Oncology, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
| | - Hans Kristian Moen Vollan
- Division of Cancer Medicine, Surgery and Transplantation, Department of Oncology, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - Anne-Lise Børresen-Dale
- K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
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Neoadjuvant therapy in operable breast cancer: application to triple negative breast cancer. JOURNAL OF ONCOLOGY 2013; 2013:219869. [PMID: 23983689 PMCID: PMC3747378 DOI: 10.1155/2013/219869] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Accepted: 07/06/2013] [Indexed: 12/31/2022]
Abstract
Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification) has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today's standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed.
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50
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Kim H, Jung K, Im SA, Im YH, Kang S, Park K, Lee S, Kim SB, Lee KH, Ahn J, Kim S, Sohn J. Multicentre phase II trial of bevacizumab combined with docetaxel–carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905). Ann Oncol 2013; 24:1485-90. [DOI: 10.1093/annonc/mds658] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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