H Bonnefoi1, S Litière2, M Piccart3, G MacGrogan4, P Fumoleau5, E Brain6, T Petit7, P Rouanet8, J Jassem9, C Moldovan10, A Bodmer11, K Zaman12, T Cufer13, M Campone14, E Luporsi15, P Malmström16, G Werutsky2, J Bogaerts2, J Bergh17, D A Cameron18. 1. Department of Medical Oncology, Institut Bergonié Comprehensive Cancer Centre, Université de Bordeaux, INSERM U916, Bordeaux, France h.bonnefoi@bordeaux.unicancer.fr. 2. European Organisation for Research and Treatment of Cancer (EORTC), Brussels. 3. Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 4. Department of Medical Oncology, Institut Bergonié Comprehensive Cancer Centre, Université de Bordeaux, INSERM U916, Bordeaux, France. 5. Centre George-François Leclerc, Dijon. 6. Ensemble Hospitalier de L'Institut Curie, Hopital René Huguenin, St-Cloud. 7. Centre Paul Strauss, Strasbourg. 8. Centre Val D'Aurelle-Paul Lamarque, Montpellier, France. 9. Medical University, Gdansk, Poland. 10. Centre Henri Becquerel, Rouen, France. 11. Geneva University Hospital, Geneva Swiss Group for Clinical Cancer Research (SAKK), Bern. 12. Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. 13. Institute of Oncology, Ljubljana University Clinic Golnik, Golnik, Slovenia. 14. Institut de Cancérologie de L'Ouest (ICO), Centre René Gauducheau, Nantes Centre Paul Papin, Angers. 15. Centre Alexis Vautrin, Nancy, France. 16. Department of Clinical Sciences, Lund University, Lund Skåne Department of Oncology, Skåne University Hospital, Lund. 17. Swedish Breast Cancer Group (SweBCG), Stockholm Department of Oncology, Karolinska Institutet, Radiumhemmet and Karolinska University Hospital, Stockholm, Sweden. 18. Cancer Services, Edinburgh University Anglo-Celtic Cooperative Oncology Group (ACCOG), Edinburgh, UK.
Abstract
BACKGROUND: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. PATIENTS AND METHODS: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. RESULTS: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). CONCLUSIONS: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. CLINICALTRIALSGOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.
BACKGROUND: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. PATIENTS AND METHODS: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. RESULTS: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). CONCLUSIONS: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. CLINICALTRIALSGOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.
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