Androgen receptor expression in patients with triple negative breast cancer treated with neoadjuvant chemotherapy: a single institution study

Abstract

Background: Androgen receptor (AR) expression has emerged as a potential prognostic and predictive marker in patients with triple negative breast cancer (TNBC). We conducted a retrospective analysis to evaluate pathologic complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS) in patients with AR positive and AR negative TNBC treated with neoadjuvant chemotherapy. Methods: 107 patients with TNBC subtype, treated with neoadjuvant chemotherapy between June 2006 and March 2016 were evaluated for AR expression. Androgen receptors were evaluated by immunohistochemical staining (clone AR441, Dilution 1:50, Dako-Agilent, Santa Clara, CA) using whole tissue sections from archived paraffin-embedded formalin-fixed (FFPE) blocks. AR positive was defined as ≥10% nuclear stained cells. Correlation of AR expression was examined with age, BMI, race, menopausal status, tumor grade, tumor size, and lymph node involvement, and response and outcomes. Univariate and multivariate analyses were performed to determine an association with AR expression and pathologic response and survival outcomes. Results: Fifty-eight patients with available tumor specimens were stained, with twenty (34.5%) being AR-positive and thirty-eight (65.5%) being AR negative. Median age was 49 years and median follow up was 5.7 years. All patients received anthracycline based neoadjuvant chemotherapy with 13 patients (23%) receiving an additional platinum chemotherapy. BRCA mutation positivity was 7% for the entire group. No differences in age, menopausal status, BMI, race, tumor size and lymph node involvement were observed between the two groups. However, there was a statistically significant difference in tumor grade between the two groups (p=0.008). Overall pCR rate was 28% with no difference between the two groups (30% vs 26%, p=0.56). There was no statistically significant difference in median DFS (5.9 years vs 5.2 years ( p =0.94) and median OS (6.2 years vs 5.4 years, p =0.98) between the AR positive and AR negative groups. Conclusions: Our study did not find an association of AR status and the pathologic responses or survival outcomes in patients with TNBC treated with neoadjuvant chemotherapy. Further studies exploring the prognostic and predictive role of AR in patients with TNBC are warranted.

The Potential of Hormonal Therapies for Treatment of Triple-Negative Breast Cancer

“…However, as described above, this is in direct contrast with most experimental results obtained so far. Furthermore, a small number of studies report that AR expression is associated with an increased rate of metastasis [59,60], while others have stated that it has no effect upon OS in TNBC [61,62]. Possible explanations for this discrepancy can include several factors such as the demographic and TNBC subtypes being analyzed, as well as the effect of different AR mutations upon patient outcome [43].…”

Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review

“…• ARs antagonists are being studied in both preclinical and clinical study for treatment of TNBC; however, currently, no reliable biomarker has been found to predict treatment efficacy (Witzel et al, 2019;Sridhar et al, 2022).…”

“…As a result, the discovery of innovative TNBC therapeutics is critical. Recently, numerous investigations have revealed that additional types of hormone receptors, such as the androgen receptor, are expressed in TNBC (Gerratana et al, 2018;Traina et al, 2018;Elghazawy et al, 2021;Sridhar et al, 2022).…”

Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy

“…At present, the research on the correlation between AR and neoadjuvant chemotherapy mainly focuses on TNBC. Some studies have shown that AR positive TNBC had a lower rate of pCR compared with AR negative TNBC [ 22 , 23 ], However, a recent research indicated that there was no association of AR status and the pathologic responses or survival outcomes in patients with TNBC treated with neoadjuvant chemotherapy [ 24 ].Studies regarding AR as a predictor of pCR rate and survival after neoadjuvant chemotherapy according to breast cancer subtype were insufficient [ 25 ]. Therefore, further studies exploring the prognostic and predictive role of AR in patients with breast cancer subtypes are warranted.…”