Institut Paoli-Calmettes, Marseille, France
Alexandre de Nonneville , Anthony Goncalves , Christophe Zemmour , Jean-Marc Classe , Monique Cohen , Eric Lambaudie , Fabien Reyal , Sylvia Giard , Roman Rouzier , Richard Villet , Jean-Marie Boher , Gilles Houvenaeghel
Background: Benefit of adjuvant Trastuzumab-based chemotherapy for node-positive and/or > 1 cm HER2+ breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidences for support adjuvant chemotherapy and/or Trastuzumab (CT+/-T) in pT1abN0 HER2+ tumors are limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy and/or Trastuzumab on outcome in this subpopulation. Methods: 245 cases of pT1abN0 HER2+ breast cancers were retrospectively identified from a large cohort of 5010 consecutive HER2+ patients who underwent primary surgery at 13 French centers, between Dec 1999 and Jan 2013. The primary endpoint was disease-free survival (DFS). A multivariate Cox model was built including adjuvant CT+/-T, tumor size and hormone receptor (HR) status. Results: A total of 102 cases (42%) were treated with CT+/-T, 23 with chemotherapy alone, 2 with Trastuzumab alone, and 118 (48%) with neither Trastuzumab nor chemotherapy. Patient characteristics were as follows (treated vs. untreated): the median follow-up was 40.07 vs. 52.85 months (p = 0.16). The median age was 53 vs. 58 years. Proportions of pT1a were 29.13 vs. 52.54%, pT1b: 70.87 vs. 47.46%, SBR grade III: 48.39 vs. 19.63%, HR-: 48.03 vs. 32.20%, HR+: 51.97 vs. 67.80%. In this last subgroup, 51.18 vs. 58.47% have had an endocrine therapy (p = 0.25). Adjuvant CT+/-T was associated with a significant 5-year DFS benefit (95% versus 86%; p = 0.049, Log-rank test), which was maintained in multivariate analysis (Hazard Ratio = 0.299; 95% CI [0.10,0.90]; p = 0.033). Exploratory subgroup analysis found this benefit to be significant in pT1b (5-year DFS of 99% versus 87%, p = 0.015) or HR-negative (5-year DFS of 97% versus 72%, p = 0.016) tumors. Conclusions: Adjuvant therapy with chemotherapy and/or Trastuzumab was associated with a significantly reduced risk of recurrence in subcentimetric node negative HER2+ breast cancers. Most of benefit may be driven by pT1b or HR-negative tumors. These data provide additional clues to the issue of adjuvant systemic treatment in these tumors.
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