title: Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy.
abstract: The androgen receptor (AR) has been shown to be of potential prognostic importance in retrospective cohorts. We evaluated immunohistochemical AR expression on a tissue microarray of 673 core biopsies from primary breast cancer patients treated with neoadjuvant docetaxel/doxorubicin/cyclophosphamide (TAC) chemotherapy in the prospective GeparTrio phase-III trial. AR was detected in 53.2% of tumours. Lowest AR expression was detected in triple-negative breast cancers (TNBC) with 21.2%. Highest AR expression was observed in Luminal A-like tumours with 67%. In AR-positive tumours, pathological complete response (pCR) rate was 12.8% compared to 25.4% in AR-negative tumours (P < 0.0001). In multivariate analysis, AR independently predicted pCR (OR 1.86; 95% CI [1.16-2.79] P = 0.0086). Overall patients with an AR-positive tumour had a significant better disease-free (DFS) (AR-positive 78.9% vs. AR-negative 72.5%; log-rank P = 0.0329) and overall survival (OS) (88.8% vs. 82.7%; log-rank P = 0.0234) than those with AR-negative tumours. Stratified analysis revealed that in the TNBC subgroup, but not in the other subgroups defined by ER, PgR and HER2, AR expression predicted a better DFS (AR-positive 85.7% vs. AR-negative 65.5% log-rank P = 0.0544) and OS (95.2% vs. 76.2%; log-rank P = 0.0355). Within the non-pCR subgroup, AR positivity selected a group with a significant better DFS (P = 0.045) and OS (0.021) but not within the pCR group. Patients with an AR-negative tumour have a higher chance of achieving a pCR than those with an AR-positive one. But, patients with AR-positive tumours have a better survival especially if they did not achieve a pCR.
authors.affiliation: German Breast Group, Martin-Behaim Str. 12, 63263 Neu-Isenburg, Germany. sibylle.loibl@germanbreastgroup.de
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Berit Maria
authors.initials: BM
authors.lastname: Müller
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Michael
authors.initials: M
authors.lastname: Schwabe
authors.forename: Marc
authors.initials: M
authors.lastname: Roller
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
authors.forename: Beyhan
authors.initials: B
authors.lastname: Ataseven
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Annette
authors.initials: A
authors.lastname: Fissler-Eckhoff
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.forename: Uwe
authors.initials: U
authors.lastname: Kulmer
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Alles
authors.forename: Keyur
authors.initials: K
authors.lastname: Mehta
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D011944:Receptors, Androgen / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide