title: Efficacy of endocrine therapy in relation to progesterone receptor and Ki67 expression in advanced breast cancer.
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 chemotherapy 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 tumors 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.
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rocca
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Farolfi
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Maltoni
authors.affiliation: Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Carretta
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Melegari
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ferrario
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cecconetto
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Samanta
authors.initials: S
authors.lastname: Sarti
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Schirone
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Fedeli
authors.affiliation: Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Andreis
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pietri
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Montalto
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy. direzione.scientifica@irst.emr.it.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone