Predictive factors of 5-year relapse-free survival in HR+/HER2- breast cancer patients treated with neoadjuvant endocrine therapy: pooled analysis of two phase 2 trials

Florence Lerebours,Jérôme Lemonnier,Hervé Bonnefoi,Véronique Becette,Brigitte Sigal,Laurence Vénat-Bouvet ,Simone Mathoulin‐Pélissier ,Emmanuelle Fourme,Marie-Ange Mouret-Reynier,Marc Debled,Jean‐Yves Pierga ,Thomas Bachelot,Marina Pulido,Sofía Rivera ,Gaëtan Macgrogan ,C Tunon De Lara ,C Breton-Callu ,Florence Dalenc,Thibault De La Motte Rouge,Nathalie Quénel-Tueux

doi:10.1038/s41416-020-0733-x

Abstract

BackgroundFew data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET).MethodsThis is a pooled analysis of two multicentre, randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patients: HORGEN (NCT00871858) and CARMINA02 (NCT00629616) studies.ResultsIn total, 236 patients were included in CARMINA02 and HORGEN trials. Modified intention-to-treat analysis was available for 217 patients. Median follow-up was 65.2 months. Relapse-free survival (RFS) and overall survival (OS) at 5 years were 83.7% (95% CI: 77.9–88) and 92.7% (95% CI: 88.2–95.6), respectively, with no difference between treatment arms. On univariate analysis, tumour staging (T2 vs T3–4; p = 0.0001), Ki-67 at surgery (≤10% vs >10%; p = 0.0093), pathological tumour size (pT1–2 vs pT3–4; p = 0.0012) and node status (pN negative vs positive; p = 0.007), adjuvant chemotherapy (p = 0.0167) and PEPI score (PEPI group I + II vs III; p = 0.0004) were associated with RFS. No events were observed in patients with pathological response according to the Sataloff classification. Multivariate analysis showed that preoperative endocrine prognostic index (PEPI) group III was associated with significantly worse RFS (p = 0.0069, hazard ratio = 3.33 (95% CI: 1.39–7.98)).ConclusionsPostmenopausal HR+/HER2- breast cancer patients receiving NET generally have a favourable outcome. The PEPI score identifies a subset of patients of poorer prognosis who are candidates for further additional treatment.

Highlights

Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET)
International guidelines consider that neoadjuvant endocrine therapy (NET) given for 4–8 months is a validated treatment in postmenopausal women presenting a hormone receptor-positive (HR+)/HER2negative (HER2-) breast cancer to improve surgical outcome and allow breast-conserving surgery (BCS).[2,3]
Trial conduct and patient’s cohort From October 2007 to April 2013, 236 patients were included, 116 in CARMINA02 and 120 in HORGEN. modified intention-to-treat (mITT) analysis was available for 217 patients

Summary

Introduction

Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET). PCR is uncommon after NET, prognosis seems favourable in most cases.[5,6] Ki-67 expression, before and especially under endocrine treatment, has been shown to predict relapse-free survival (RFS) in the IMPACT trial.[7,8] Based on patients included in the P024 trial, Ellis et al developed a preoperative prognostic index (PEPI score) validated in an independent cohort of patients from the IMPACT study.[5,9,10] It combines the post-treatment Ki-67 level with ER status, pathological tumour size and nodal status

Methods

Results

Conclusion