Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial

Abstract

Importance: Neoadjuvant systemic therapy (NST) is often administered to enable breast-conserving therapy (BCT) in stages II to III breast cancer.

Objectives: To prospectively evaluate the role of NST in conversion from BCT ineligibility to BCT eligibility and to assess the association of response to NST, germline BRCA (gBRCA) status, and region of treatment with surgical choice in women with triple-negative breast cancer (TNBC).

Design, setting, and participants: This prespecified secondary analysis of a multicentered, phase 3, double-blind, randomized clinical trial (BrighTNess) enrolled 634 eligible women across 145 centers in 15 countries in North America, Europe, and Asia. Women with operable, clinical stages II to III TNBC who underwent gBRCA mutation testing before initiating NST were eligible to participate. Data were collected from April 1, 2014, to December 8, 2016. This preplanned analysis was performed from January 5, 2018, to October 28, 2019.

Interventions: Study participants were randomized to receive 12 weeks of weekly paclitaxel alone or with the addition of carboplatin and/or veliparib, followed by 4 cycles of doxorubicin hydrochloride and cyclophosphamide.

Main outcomes and measures: Surgeons assessed BCT candidacy by clinical and radiographic criteria before and after NST. Surgical choices and whether BCT eligibility was associated with the likelihood of pathologic complete response were then analyzed.

Results: Among the 634 randomized patients (median age, 51 [range, 22-78] years), pre- and post-NST assessments were available for 604 patients. Of 141 patients deemed BCT ineligible at baseline, 75 (53.2%) converted to BCT eligible. Overall, 342 (68.1%) of 502 patients deemed BCT eligible after NST underwent BCT, including 42 (56.0%) of the 75 who converted to BCT eligible. Patients treated in Europe and Asia were more likely to undergo BCT (odds ratio, 2.66; 95% CI, 1.84-3.84) compared with those treated in North America. Among patients without gBRCA mutation undergoing mastectomy, those treated in North America were more likely to undergo contralateral prophylactic mastectomy (57 of 81 [70.4%] vs 6 of 30 [20.0%]; P < .001). Rates of pathologic complete response were similar between patients deemed BCT eligible at baseline and those who were BCT ineligible but converted to BCT eligibility after NST (55.3 [235 of 425] vs 49.3% [37 of 75]; P = .38).

Conclusions and relevance: This prospective analysis of NST and BCT eligibility in TNBC demonstrates a conversion from BCT ineligibility to BCT eligibility of 53.2%. Lower BCT rates among eligible patients and higher bilateral mastectomy rates among patients without gBRCA mutation in North America merit investigation.

Trial registration: ClinicalTrials.gov identifier: NCT02032277.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Golshan reported serving as a scientific advisor on a steering committee for AbbVie, Inc, during the conduct of the study. Dr Loibl reported receiving grants, personal fees, and nonfinancial support from AbbVie, Inc, and grants from Myriad Genetics during the conduct of the study and grants and nonfinancial support from AstraZeneca and Pfizer, Inc, outside the submitted work. Dr Houber reported receiving personal fees from AbbVie, Inc, AstraZeneca, Celgene Corporation, and Pfizer, Inc, outside the submitted work. Dr O’Shaughnessy reported receiving personal fees from AbbVie, Inc, Agendia, Amgen Biotechnology, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Eisai Co, Ltd, Genentech, Inc, Genomic Health, GRAIL, Inc, Immunomedics, Heron Therapeutics, Inc, Ipsen Biopharmaceuticals, Inc, Eli Lilly and Company, Merck & Co, Myriad Genetics, Novartis International AG, Ondonate Therapeutics, Inc, Pfizer, Inc, Puma Biotechnology, Inc, Roche Diagnostics, Seattle Genetics, and Syndax Pharmaceuticals, Inc, during the conduct of the study. Dr Rugo reported receiving grants from Pfizer, Inc, Merck & Co, Novartis International AG, Eli Lilly and Company, Genentech, Inc, OBI Pharma, Inc, Odonate Therapeutics, Eisai Co, Ltd, Seattle Genetics, and MacroGenics, Inc and serving as a scientific advisor for Eli Lilly and Company, Mylan Pharmaceuticals, Inc, Pfizer, Inc, Amgen, Inc, Merck & Co, and Puma Biotechnology, Inc, outside the submitted work. Dr McKee reported other from AbbVie, Inc, during the conduct of the study. Dr Sullivan reported ownership of stock in AbbVie, Inc. Dr von Minckwitz reported receiving grants from AbbVie, Inc, during the conduct of the study and grants from Pfizer, Inc, Celgene Corporation, AstraZeneca, Myriad Genetics, and Vifor Pharma and grants and personal fees from Amgen and Roche Diagnostics outside the submitted work. Dr Geyer reported receiving nonfinancial support from AbbVie, Inc, during the conduct of the study and grants and nonfinancial support from Genentech/Roche, nonfinancial support from AstraZeneca, and personal fees from Celgene Corporation outside the submitted work. Dr Sikov reported serving as a scientific advisor on a steering committee for AbbVie, Inc, during the conduct of the study. Dr Untch reported serving as a scientific advisor on a steering committee for AbbVie, Inc, during the conduct of the study and receiving personal fees from Amgen Biotechnology, AstraZeneca, Celgene Corporation, Daiiji Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp, Mundipharma, Myriad Genetics, Pfizer, Inc, F. Hoffmann-La Roche, Ltd, and Teva Pharmaceutical Industries, Ltd, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Flow Diagram

BCT indicates breast-conserving therapy; NST, neoadjuvant systemic therapy.

Figure 2.. Candidacy for Breast-Conserving Therapy (BCT) Before and After Completion of Neoadjuvant Systemic Therapy (NST)

pCR indicates pathologic complete response.