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

Abstract

Background Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET). Methods This 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. Results In 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)). Conclusions Postmenopausal 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.

The Role of Ki67 in Evaluating Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer

“…Reduction in Ki67 >40% between pretreatment and 10–14 days was related to pathological responses. A pooled analysis of two multicenter, randomized, noncomparative, phase 2 clinical trials (HORGEN and CARMINA02) evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer indicated that PEPI can identify a subset of patients with poorer prognosis who should be offered all appropriate adjuvant therapy ( 55 ). Ki67 in neoadjuvant trials predicted the long-term outcomes of large adjuvant trials; Ki67 and PEPI can be predictors for evaluating the recurrence-free survival of breast cancer patients with NET ( 50 ).…”

Neoadjuvant Endocrine Therapy in Breast Cancer Management: State of the Art

“…The NEWEST trial compared 16 weeks of neoadjuvant fulvestrant at doses of 250 to 500 mg. Tumor response rates at week 16 were similar between the two dosages (22.9 and 20.6%, respectively) [ 17 ]. We recently published a pooled analysis of two sister phase II trials evaluating anastrozole and fulvestrant as NET in postmenopausal HR+/HER2- breast cancer patients (CARMINA02 and HORGEN trials) [ 18 , 19 , 20 ]. These two trials had a similar design and included similar populations and the primary endpoint in both studies was clinical response rate at 6 months.…”

“…In our pooled analysis of the CARMINA02 and HORGEN trials, we used the Sataloff classification to assess the pathological response rate and its prognostic value after NET [ 18 ]. Somewhat similar to the RCB score, the Sataloff classification examines the therapeutic effect of neoadjuvant therapy by measuring the reduction in tumor cell number in breast and nodes [ 48 ].…”

“…Although the tumor burden often remains high, with persistent node involvement when initially present, NET-treated patients often have a good prognosis [ 38 , 50 , 51 , 52 ]. We found a 5-year relapse-free survival (RFS) rate of 83.7% and an overall survival rate of 92.7% in our a pooled analysis involving 217 postmenopausal women treated with anastrozole or fulvestrant for 4 to 6 months before surgery (in a population with 75% T2, 35% of which had initial lymph node involvement, and 70% grade II tumors) [ 18 ]. Interestingly, adjuvant chemotherapy, which was administered to 21.7% of patients according to each center’s local policy, was not correlated with prognosis on multivariate analysis.…”

“…We also evaluated prognosis based on the PEPI score in 217 patients treated with anastrozole or fulvestrant in the pooled analysis of CARMINA02 and HORGEN trials [ 18 ]. In this pooled analysis, PEPI group III (score ≥ 4) compared with PEPI groups I or II was the only variable significantly associated with poorer 5-year RFS on multivariate analysis.…”