The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: a analysis of the IBIS 3 trial

• Main Authors: Sara Bravaccini, Giuseppe Bronte, Emanuela Scarpi, Sara Ravaioli, Roberta Maltoni, Anita Mangia, Maria Maddalena Tumedei, Maurizio Puccetti, Patrizia Serra, Lorenzo Gianni, Laura Amaducci, Nicoletta Biglia, Valentina Bounous, Angelo Virgilio Paradiso, Rosella Silvestrini, Dino Amadori, Andrea Rocca
• Format: Article
• Language: English
• Published: SAGE Publishing 2020-02-01
• Series: Therapeutic Advances in Medical Oncology
• Online Access: https://doi.org/10.1177/1758835919888999

Background: In the Italian Breast Cancer Intergroup Studies (IBIS) 3 phase III trial, we compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF) alone to sequential epirubicin/CMF regimens in patients with rapidly proliferating early breast cancer (RPEBC). We performed a post hoc analysis in the subgroup of patients with hormone-receptor-positive RPEBC on the prognostic role of progesterone receptor (PgR) status. Methods: RPEBC was defined by thymidine labeling index (TLI) >3% or grade 3 or S-phase >10% or Ki67 >20%. We analyzed 466 patients with hormone-receptor-positive RPEBC receiving sequential epirubicin/CMF regimens followed by tamoxifen, and for whom the status of ER and PgR was available. Results: Considering both cut-off values of 10% and 20%, PgR expression was significantly associated with age, menopausal status, and ER expression; HER2 status was associated with PgR status only at a cutoff value of 20% PgR. Upon univariate analysis, tumor size, nodal status, and PgR were significantly associated with disease-free survival (DFS) and overall survival (OS), while age class and local treatment type were associated only with DFS. Patients with PgR <20% showed lower 5- and 10-year DFS [hazard ratio (HR) = 1.48; 95%CI: 1.01–2.18; p  = 0.044] and OS (HR = 1.85; 95%CI: 1.08–3.19, p  = 0.025) rates compared with patients with PgR ⩾20%. Upon multivariate analysis, only tumor size, nodal status, and PgR were independent prognostic factors. Conclusions: Our results highlight the independent prognostic relevance of PgR expression in patients with hormone-receptor-positive RPEBC treated with adjuvant chemotherapy and endocrine therapy, where the definition of prognostic subgroups is still a major need.