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Neoadjuvant and Adjuvant Chemotherapy Considerations for Triple-Negative Breast Cancer

Daniel G. Stover, MD; Caitlin F. Bell; Sara M. Tolaney, MD, MPH
Published: Monday, May 02, 2016

Daniel G. Stover, MD

Daniel G. Stover, MD

Abstract

Triple-negative breast cancers (TNBC) are an immunohistochemically defined subset of breast cancer that is negative for the estrogen receptor (ER), progesterone receptor (PR), and HER2, and represent a heterogeneous group of tumors based on expression profiling. Despite strides made in adjuvant chemotherapy regimens and in overall survival for patients with breast cancer, prognosis for patients with TNBC continues to lag behind those with ER+ or HER2+ tumors. Chemotherapy remains the standard of care for TNBC because no targeted therapies have been proven to be effective for this subtype. There is growing interest in the use of platinum agents in the neoadjuvant setting for TNBC but we await data from ongoing, randomized, adjuvant trials to understand if these agents have an impact on long-term outcomes. Patients with BRCA-mutant TNBC are a special subgroup who may benefit more from platinums and, potentially, from poly ADP ribose polymerase (PARP) inhibitors. Immune checkpoint inhibitors are promising in many cancer types and are investigational in combination with chemotherapy in the neoadjuvant setting. Growing attempts to develop biomarkers to guide therapy within TNBC may lead to more effective regimens or to novel therapeutic targets.

Introduction: Defining the Subtype

Triple-negative breast cancers (TNBC), defined by the absence of estrogen (ER), progesterone (PR), and HER2 receptors, account for approximately 15% of all breast cancers.1 This subtype is more common in African-American women, younger women, and BRCA1 mutation carriers.1,2 They are disproportionately associated with early recurrences, particularly in the first 5 years after diagnosis, with recurrences that are more commonly visceral or CNS rather than bone.3,4 Hormone receptor-positive breast cancer recurs at a rate of 3% to 5% per year over a patient’s lifetime, while TNBC recurs at a rate of 10% to 15% per year for 3 years before declining.2,5 In an analysis of nearly 45,000 women with a first primary breast cancer who were registered in the California Cancer Registry, TNBC had a 5-year survival rate of 77% compared to 93% for other subtypes.6

There is growing interest in molecular classification of breast cancers as we move towards precision medicine for this disease.7 Genomic analyses of TNBC, including sequencing of several hundred primary TNBCs, revealed frequent mutation in TP53 but few recurrent targetable mutations.8,9 Mutations in DNA repair pathways are more common in TNBC relative to other breast cancer subtypes. There is particular interest in BRCA1 mutation carriers, since about 70% of breast cancers that develop in this group are triple-negative.10 However, BRCA1 mutation carriers remain a minority among all TNBC, with 10% to 25% germline or somatic BRCA1 mutation in most series11,12 (Figure 1).




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TitleExpiration DateCME Credits
Oncology Best Practice™: Choosing Therapies for Patients with EGFR-Mutant Lung Cancers: More Options... More Decisions... Better OutcomesFeb 28, 20182.0
Clinical Vignette Series: 34th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow®Feb 28, 20182.0
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