Alexandre de Nonneville1,2, Anthony Gonçalves3,4, Christophe Zemmour5, Jean M Classe6, Monique Cohen7, Eric Lambaudie4,7, Fabien Reyal8, Christophe Scherer9, Xavier Muracciole10, Pierre E Colombo11, Sylvia Giard12, Roman Rouzier13, Richard Villet14, Nicolas Chopin15, Emile Darai16, Jean R Garbay17, Pierre Gimbergues18, Laura Sabiani19, Charles Coutant20, Renaud Sabatier3,4, François Bertucci3,4, Jean M Boher5, Gilles Houvenaeghel4,7. 1. Department of Medical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France. alexandredenonneville@gmail.com. 2. Aix-Marseille University, Marseille, France. alexandredenonneville@gmail.com. 3. Department of Medical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France. 4. Aix-Marseille University, Marseille, France. 5. Department of Clinical Research and Investigation, Biostatistics and Methodology UnitInstitut Paoli Calmettes, Marseille, France. 6. Institut René Gauducheau, St Herblain, France. 7. Department of Surgical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France. 8. Institut Curie, Paris, France. 9. Pôle Santé République, Clermont-Ferrand, France. 10. Department of Radiotherapy, Hôpital de la Timone, Marseille, France. 11. Department of Surgical Oncology, CRLC Val-d'Aurelle, Montpellier, France. 12. Centre Oscar Lambret, Lille, France. 13. Centre René Huguenin, Saint Cloud, France. 14. Hôpital des Diaconnesses, Paris, France. 15. Department of Surgical Oncology, Centre Léon Bérard, Lyon, France. 16. Department of Gynecologic and Breast Cancers, Hôpital Tenon, Paris, France. 17. Department of Surgical Oncology, Gustave-Roussy, Villejuif, France. 18. Department of Surgical Oncology, Centre Jean-Perrin, Clermont-Ferrand, France. 19. Department of Obstetrics Gynecology, Hôpital de la Conception, Marseille, France. 20. Department of Surgical Oncology, Centre Georges-François Leclerc, Dijon, France.
Abstract
PURPOSE: Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation. PATIENTS AND METHODS: A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade. RESULTS: A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors. CONCLUSIONS: Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.
PURPOSE: Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1 cm humanepidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation. PATIENTS AND METHODS: A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade. RESULTS: A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors. CONCLUSIONS: Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.
Entities:
Keywords:
Adjuvant chemotherapy; HER2; Subcentimetric breast cancer; Trastuzumab