J Clin Oncol 2015 Aug 22;33(24):2600-8. Epub 2015 Jun 22.
Ciara C. O'Sullivan and Jo Anne Zujewski, National Cancer Institute, Bethesda, MD; Ian Bradbury, Christine Campbell, and Eileen Holmes, Frontier Science, Inverness-shire, Scotland; Marc Spielmann and Suzette Delaloge, Institut de Cancérologie Gustave Roussy, Villejuif, France; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Heikki Joensuu, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Joseph P. Costantino and Priya Rastogi, University of Pittsburgh, Pittsburgh, PA; Dimitrios Zardavas, Breast International Group; Karla V. Ballman, Mayo Clinic, Rochester, MN; Evandro de Azambuja and Martine Piccart-Gebhart, Institut Jules Bordet and L'Université Libre de Bruxelles, Brussels, Belgium; and Richard D. Gelber, Harvard Medical School, Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, and Frontier Science and Technology Research Foundation, Boston, MA.
Purpose: We compared efficacy of trastuzumab versus no trastuzumab in patients with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) -positive breast cancer treated in randomized trials.
Methods: A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) -positive and HR-negative cohorts. Random effect models and Yusuf-Peto fixed effects models assessed the impact of heterogeneity on baseline hazards and treatment effects across studies. Peto-Pike cumulative incidence estimates were stratified by study and nodal status.
Results: Median follow-up time was 8 years. For 2,263 patients with HR-positive disease, 8-year cumulative incidence rates comparing trastuzumab versus no trastuzumab were 17.3% versus 24.3% (P < .001) for DFS and 7.8% versus 11.6% (P = .005) for OS, respectively; for 1,092 HR-positive patients with zero or one positive lymph nodes, results were 12.7% versus 19.4% (P = .005) for DFS and 5.3% versus 7.4% (P = .12) for OS, respectively. For 1,957 patients with HR-negative disease, 8-year cumulative incidence rates were 24.0% versus 33.4% (P < .001) for DFS and 12.4% versus 21.2% (P < .001) for OS, respectively; for 1,040 HR-negative patients with zero or one positive lymph nodes, results were 20.4% versus 26.3% (P = .05) for DFS and 8.2% versus 12.2% (P = .084) for OS, respectively.
Conclusion: Women with HER2-positive tumors ≤ 2 cm in the randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastuzumab. Trastuzumab-treated patients with HR-positive disease and ≤ one positive lymph node may be candidates for trials assessing less aggressive treatment approaches.