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Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)

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Abstract

Purpose

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).

Methods

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.

Results

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).

Conclusion

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.

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Genentech provided funding for the conduct of this trial.

Author information

Author notes

  1. Clifford A. Hudis

    Present address: American Society of Clinical Oncology, Alexandria, VA, USA

Authors and Affiliations

  1. Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, 450 Brookline Avenue, Boston, MA, USA

    Jennifer R. Bellon

  2. Department of Statistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Hao Guo & William T. Barry

  3. Breast Cancer Medicine Service, Solid Tumor Division, Department of Medicine, Memorial Sloan Kettering Cancer Center and Department of Medicine, Weill Cornell Medical Center, New York, NY, USA

    Chau T. Dang & Clifford A. Hudis

  4. Department of Medical Oncology, Sarah Cannon Cancer Center, Nashville, TN, USA

    Denise A. Yardley

  5. Department of Hematology–Oncology, Massachusetts General Hospital, Boston, MA, USA

    Beverly Moy

  6. Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Durham, NC, USA

    P. Kelly Marcom

  7. Division of Hematology/Oncology, Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA

    Kathy S. Albain

  8. Department of Medicine, Division of Oncology, Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USA

    Hope S. Rugo

  9. Department of Medical Oncology, Baylor Clinic-Lester and Sue Smith Breast Center, Houston, TX, USA

    Matthew Ellis

  10. Department of Oncology, Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA

    Antonio C. Wolff

  11. Department of Medical Oncology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    Lisa A. Carey

  12. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Beth A. Overmoyer, Ann H. Partridge, Ian Krop, Harold J. Burstein, Eric P. Winer & Sara M. Tolaney

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  1. Jennifer R. Bellon
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Corresponding author

Correspondence to Jennifer R. Bellon.

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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.

Ethical approval

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.

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Informed consent was obtained from all individual participants included in the study.

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Bellon, J.R., Guo, H., Barry, W.T. et al. Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial). Breast Cancer Res Treat 176, 303–310 (2019). https://doi.org/10.1007/s10549-019-05238-4

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