CLINICAL TRIAL Efficacy of endocrine therapy in relation to progesterone receptor and Ki67 expression in advanced breast cancer Andrea Rocca 1 • Alberto Farolfi 1 • Roberta Maltoni 1 • Elisa Carretta 2 • Elisabetta Melegari 1 • Cristiano Ferrario 1 • Lorenzo Cecconetto 1 • Samanta Sarti 1 • Alessio Schirone 1 • Anna Fedeli 1 • Daniele Andreis 2 • Elisabetta Pietri 1 • Toni Ibrahim 1 • Erika Montalto 1 • Dino Amadori 1 Received: 12 December 2014 / Accepted: 8 May 2015 Ó Springer Science+Business Media New York 2015 Abstract We assessed whether progesterone receptor (PgR) and Ki67 in primary tumors and/or matched metastases are predictors of clinical benefit from first-line endocrine therapy (ET) in advanced breast cancer. We evaluated patients treated at our institute with first-line ET (2002–2011), excluding those receiving concomitant che- motherapy or trastuzumab or pretreated with [ 2 lines of chemotherapy. A cut-off of 20 % immunostained cells was used for PgR and Ki67. The main endpoint was time-to- progression (TTP). Groups were compared by the log-rank test and Cox multivariate analysis. In the 135 assessable patients (93 % were receiving an aromatase inhibitor; biomarker assessment had been performed on primary tu- mors in 77 cases, on metastases in 23 and on both in 35), median TTP was 16 months (median follow-up 43 months). The overall discordance rate between primary tumors and metastases was 23 % for Ki67 and 31 % for PgR. A longer median TTP (24 vs. 12 months, P = 0.012) was seen for PgR [ 20 % in metastases. Ki67 showed a trend for TTP prediction in the entire case series (P = 0.062). Patients with high Ki67 and low PgR in metastases had a median TTP of only 5 months. High Ki67 in primary tumors (P = 0.026) or metastases (P = 0.01) predicted disease progression at the first evaluation. PgR in metastases remained a significant independent predictor of TTP at multivariate analysis (HR 2.45). In an ER-high population, PgR [ 20 % in metastases identified patients with a long TTP on endocrine treatment, while Ki67 [ 20 % was associated with an increased risk of non- response. Keywords Endocrine therapy Á Advanced breast cancer Á Ki67 Á Progesterone receptor Á Luminal breast cancer Introduction Endocrine therapy is the first-line treatment of choice for patients with hormone receptor-positive advanced breast cancer (ABC), excluding those with important symptoms or life-threatening visceral involvement and rapidly pro- gressive disease [1]. However, only about 50 % of patients experience a clinical benefit [2], making it vital to identify predictors of treatment efficacy in this setting. In addition to estrogen receptor (ER) expression, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 labeling index have been studied as predictors of response, both singly and combined, to obtain surrogate definitions of breast cancer subtypes [3, 4]. Particular at- tention has been devoted to distinguishing luminal A from luminal B breast cancer subtypes due to its potential im- plications on response to chemotherapy and endocrine treatment. A Ki67 cut-off of 14 % proposed by Cheang to discriminate between luminal A and luminal B tumors [3] was endorsed at the 2011 St. Gallen International Breast Cancer Conference [5]. Further debate at the 2013 St. Gallen meeting led to the cut-off being modified to 20 % [6]. PgR [ 20 %, in association with Ki67 \ 14 % and HER2 negativity, have also been proposed to identify lu- minal A breast cancers [4]. & Dino Amadori direzione.scientifica@irst.emr.it 1 Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014 Meldola, Italy 2 Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy 123 Breast Cancer Res Treat DOI 10.1007/s10549-015-3423-2