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The role of the AR/ER ratio in ER-positive breast cancer patients

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Rangel, Nelson
Rondon-Lagos, Milena
Annaratone, Laura
Osella-Abate, Simona
Metovic, Jasna
Mano, Maria Piera
Bertero, Luca
Cassoni, Paola
Sapino, Anna
Castellano, Isabella

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2018

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BioScientifica Ltd.

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Abstract
The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of >2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER>2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER>2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER less than 2. Multivariate analysis confirmed that patients with AR/ER>2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, both P less than 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio >2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER>2 could be non-luminal tumours. © 2018 Society for Endocrinology Printed in Great Britain Published by Bioscientifica Ltd.
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Androgen receptor , androgen , Estrogen receptor , Ki 67 antigen , Progesterone receptor , Tumor marker , Androgen receptor , Ar protein , Estrogen receptor , Adult , Aged , Article , Cancer grading , Cancer patient , Cancer prognosis , Cancer recurrence , Cancer survival , Cohort analysis , Controlled study , Disease free interval , Disease specific survival , Estrogen receptor positive breast cancer , Female , Histopathology , Human , Human tissue , Immunohistochemistry , Luminal a breast cancer , Luminal b breast cancer , Lymph node metastasis , Major clinical study , Mastectomy , Partial mastectomy , Recurrence risk , Retrospective study , Survival rate , Tumor volume , Breast tumor , Metabolism , Middle aged , Pathology , Prognosis , Very elderly , Adult , Aged , Aged, 80 and over , Breast neoplasms , Female , Humans , Middle aged , Prognosis , Receptors , Receptors , Androgen receptor , Breast cancer , Oestrogen receptor , Prosigna , Subtypes
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