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Breast Cancer Research and Treatment

, Volume 176, Issue 2, pp 303–310 | Cite as

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

  • Jennifer R. BellonEmail author
  • Hao Guo
  • William T. Barry
  • Chau T. Dang
  • Denise A. Yardley
  • Beverly Moy
  • P. Kelly Marcom
  • Kathy S. Albain
  • Hope S. Rugo
  • Matthew Ellis
  • Antonio C. Wolff
  • Lisa A. Carey
  • Beth A. Overmoyer
  • Ann H. Partridge
  • Clifford A. Hudis
  • Ian Krop
  • Harold J. Burstein
  • Eric P. Winer
  • Sara M. Tolaney
Clinical Trial

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.

Keywords

HER2 Stage I Local regional recurrence Breast cancer 

Notes

Funding

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.

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.

Informed consent

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

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jennifer R. Bellon
    • 1
    Email author
  • Hao Guo
    • 2
  • William T. Barry
    • 2
  • Chau T. Dang
    • 3
  • Denise A. Yardley
    • 4
  • Beverly Moy
    • 5
  • P. Kelly Marcom
    • 6
  • Kathy S. Albain
    • 7
  • Hope S. Rugo
    • 8
  • Matthew Ellis
    • 9
  • Antonio C. Wolff
    • 10
  • Lisa A. Carey
    • 11
  • Beth A. Overmoyer
    • 12
  • Ann H. Partridge
    • 12
  • Clifford A. Hudis
    • 3
    • 13
  • Ian Krop
    • 12
  • Harold J. Burstein
    • 12
  • Eric P. Winer
    • 12
  • Sara M. Tolaney
    • 12
  1. 1.Department of Radiation OncologyDana-Farber Cancer Institute and Brigham and Women’s HospitalBostonUSA
  2. 2.Department of Statistics and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  3. 3.Breast Cancer Medicine Service, Solid Tumor Division, Department of Medicine, Memorial Sloan Kettering Cancer Center and Department of MedicineWeill Cornell Medical CenterNew YorkUSA
  4. 4.Department of Medical OncologySarah Cannon Cancer CenterNashvilleUSA
  5. 5.Department of Hematology–OncologyMassachusetts General HospitalBostonUSA
  6. 6.Division of Medical Oncology, Department of MedicineDuke Cancer InstituteDurhamUSA
  7. 7.Division of Hematology/Oncology, Department of Medicine, Cardinal Bernardin Cancer CenterLoyola University Chicago Stritch School of MedicineMaywoodUSA
  8. 8.Department of Medicine, Division of Oncology, Helen Diller Comprehensive Cancer CenterUniversity of CaliforniaSan FranciscoUSA
  9. 9.Department of Medical OncologyBaylor Clinic-Lester and Sue Smith Breast CenterHoustonUSA
  10. 10.Department of OncologyJohns Hopkins Kimmel Cancer CenterBaltimoreUSA
  11. 11.Department of Medical Oncology, UNC Lineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel HillUSA
  12. 12.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  13. 13.American Society of Clinical OncologyAlexandriaUSA

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