Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial
Menée à partir de données portant sur 1 212 patientes atteintes d'un cancer du sein et incluses dans un essai de phase III évaluant une chimiothérapie néoadjuvante par anthracycline ou docétaxel combiné ou non à l'éprirubicine, cette étude montre que la réponse pathologique complète après traitement néoadjuvant peut, indépendamment des autres facteurs, prédire la survie sans événement quel que soit le sous-type tumoral
Background : Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neo-adjuvant chemotherapy trial, we sought to determine if 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 2011St 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%) out of 1856 patients randomized. pCR occurred in 222/1212 (18%) patients: 37/496 (7.5%) luminal A, 22/147 (15%) luminal B/HER2-negative, 51/230 (22%) luminal B/HER2-positive, 43/118 (36%) HER2-positive/non luminal, 69/221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS (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.
Annals of Oncology , résumé, 2014