Abstract P5-08-30: Androgen receptor in early breast cancer: Distribution and prognostic value

Abstract

Purpose: Androgen receptor (AR) status in breast cancer has received renewed interest over the last years especially in triple-negative disease (TNBC), but the prognostic value is still under debate. The aim of this study was to assess the distribution and prognostic value of AR in early breast cancer patients with or without adjuvant endocrine treatment. Patients and methods: AR was assessed on tissue microarray with the AR 441 antibody (Thermo Scientific) on a cohort consisting of 471 patients derived from two clinical studies: (1) 208 premenopausal node-negative patients of which 87% had received no adjuvant medical treatment and (2) 263 estrogen receptor (ER)+ and ER-, node-positive and –negative patients treated with 2 years of adjuvant tamoxifen. Nuclear AR was divided in 5 groups: 0-1%, 2-10%, 11-50%, 51-75%, and 76-100% positive cells, scored as 0-4. Cox proportional hazards regression, stratified by study, was used to model the impact of the prognostic factors on distant disease-free survival (DDFS), both using trend tests and a cut-off for positivity set at >10%, and log-rank tests to compare survival in different strata. Due to non-proportional hazards, the analysis was restricted to the first 5 years after diagnosis, a time period during which 95 patients developed distant recurrences. Results: 76% of all patients were AR+, and 89%, 48%, and 23% of the ER+, ER-, and TNBC, respectively. Positive associations were observed between AR, ER and progesterone receptor status (PgR), negative associations with Ki67, and histological grade, but no associations with tumour size, age or Human Epidermal Growth Factor Receptor 2 (HER2). In univariable analysis, when divided into 5 groups, AR was a prognostic factor for DDFS with a Hazard Ratio (HR) of 0.86 per step in fraction score (95% Confidence Interval (CI): 0.76-0.98, p=0.018), as was HER2, age, size, grade, node-status, PgR, and ER status. In the Kaplan-Meier curves for each study, a similar but weaker trend was found (log-rank test for trend p=0.14 and 0.057 for cohort 1 and 2, respectively). With a cut-off at 10%, a similar HR was found (HR=0.67, 95% CI:0.43-1.05, p=0.078). In multivariable analysis, adjusted for grade, tumour size, HER2, ER, node-status, and age, AR did not retain independent prognostic value (HR 1.04 95% CI:0.88-1.23, p=0.66). In the TNBC patients there were no significant differences in DDFS in the AR+ vs AR-patients, possibly due to few events and a small population (n=20/75). Conclusion: This study demonstrates that AR is a weak prognostic factor for recurrence in a cohort consisting of node-negative premenopausal patients without endocrine treatment and patients who have received adjuvant endocrine treatment. There was however no independent value in multivariable analyses. It is noteworthy that there were 23% AR positive TNBC patients, for whom there is currently no available targeted treatment. There are several ongoing studies with AR-targeted treatment in the metastatic setting, which if proven effective, may be transferred to studies in the adjuvant setting with the goal of improving long-term prognosis for TNBC. Taken together, AR may be clinically helpful for prognostic considerations and for selection of adjuvant treatment. Citation Format: Werner-Hartman L, Folkesson E, Nodin B, Malmström P, Fernö M, Nimeus E, Klintman M. Androgen receptor in early breast cancer: Distribution and prognostic value. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-30.