Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)
Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local–regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).
Patients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan–Meier method.
Of the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4–96.2), and LRR-free survival was 98.6% (95% CI 97.4–99.8).
LRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy.
KeywordsHER2 Stage I Local regional recurrence Breast cancer
Genentech provided funding for the conduct of this trial.
Compliance with ethical standards
Conflict of interest
JB receives honorarium from UpToDate, Wolters Kluwer, The International Journal of Radiation Oncology, Biology and Physics, Leidos Pharmaceuticals, Accuray, and research funding from Prosigna. WTB reports research funding (institution) from Pfizer. CTD has received institutional research funding from and has served as advisor/consultant for Roche/Genentech, PUMA, Pfizer, Amgen, GlaxoSmithKline; in last 2 years CTD has received institutional research funding from Roche/Genentech and PUMA. BM receives institutional research funding from Puma Biotechnology. KSA has received one-time advisory board honoraria (with travel reimbursements) from Genentech/Roche, Genomic Health Inc, Novartis, Pfizer and Myriad and from Puma (as chair of an IDMC). ACW receives institutional research funding from Biomarin, Celldex, and Pfizer.BAO receives institutional research funding from Eisai, Incyte. IEK receives institutional research funding from Genentech/Roche and Pfizer and served as an advisor/consultant and received honoraria from Genentech/Roche, Daiichi/Sankyo, Macrogenomics, Context Therapeutics, Seattle Genetics and Taiho Oncology. EPW has served as an advisor to Genentech/Roche, Eli Lilly, and GSK, and serves on the Scientific Advisory Board for Leap Therapeutics. SMT receives institutional research funding from Novartis, Genentech, Eli Lilly, Pfizer, Merck, Exelixis, Eisai, Bristol Meyers Squibb, AstraZeneca, Cyclacel, Immunomedics, Odenate, and Nektar. SMT has served as an advisor/consultant to Novartis, Eli Lilly, Pfizer, Merck, AstraZeneca, Eisai, Puma, Genentech, Immunomedics, Nektar, Tesaro, Bristol Meyers Squibb, and Nanostring.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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