Abstract P5-11-07: The significance of androgen receptor co-expression in ER+ metastatic breast cancer patients treated with palbociclib
Authors: CA Landry, M Ru, S Jaffer, M Dimitrova, A Tiersten
Journal: Cancer Research (2019)

Abstract Background: The PALOMA-1 and PALOMA-3 studies demonstrated a significant progression-free survival (PFS) advantage for palbociclib, a CDK4/6 inhibitor, in combination with letrozole or fulvestrant in the first or second line setting compared to these therapies alone in estrogen receptor (ER)+, HER2-negative metastatic breast cancer (MBC). Recent studies have revealed preliminary efficacy signals for androgen receptor (AR) blockade in MBC, predominately in AR+, triple negative patients. We sought to further evaluate AR expression and its significance in ER+ MBC patients treated with palbociclib early in their metastatic treatment course. Methods: A retrospective review identified 22 patients treated with palbociclib for ER+, HER2- MBC after its FDA approval between January 1st, 2015 and October 1st, 2016 at our center with available pre-treatment tumor samples for analysis. Records were reviewed and clinical characteristics for each patient were analyzed. Archival tumor tissue was tested for AR, phosphorylated retinoblastoma (pRb), CDK6, p16, and CyclinE1 by immunohistochemistry assay for each patient. For AR, nuclear staining &amp;gt;0% was considered positive. For all other IHC studies, intensity of staining &amp;gt;2+ or staining in &amp;gt;10% of cells was considered positive. Results: The median age was 63.5 years (range 34-84); 23% were ≥ age 70. Our cohort was 35% African American, 60% Caucasian, and 5% Asian American. 64% of patients were post-menopausal and 59% had visceral metastases. 45% of patients were on their first line of treatment, 23% second line, and 32% third line. 68% of patients were on an aromatase inhibitor. Median follow up was 18.7 months (95% CI 13.9, 23.3 months). The AR was expressed in 59% of patients; 55% had expression &amp;gt;10% and 41% had expression &amp;gt;20%. AR+ patients were significantly more likely to experience event-free survival (EFS) (HR 0.26, p=0.01), with a median EFS of 18.8 months (AR- median EFS 5.4 months). AR expression was significantly associated with expression of pRb (100% of AR+ patients, p=0.02). CDK6, p16, and CyclinE1 expression were not associated with AR expression or EFS. Conclusions: Our data show preliminary evidence of the significance of ER and AR co-expression in ER+, HER2- MBC. ER+, AR+ patients have significantly improved EFS when treated with palbociclib and endocrine therapy as compared with AR-, ER+ patients. There is evidence that AR expression is associated with pRB expression, which may represent a mechanism by which cell cycle inhibition with palbociclib is particularly efficacious in these patients. AR expression rates in ER+, HER2- MBC are significant, and may provide rationale for combining CDK4/6 inhibitors with AR targeting as a subsequent line of targeted therapy in these patients before cytotoxic chemotherapy is initiated. Further studies based on these results are underway. Citation Format: Landry CA, Ru M, Jaffer S, Dimitrova M, Tiersten A. The significance of androgen receptor co-expression in ER+ metastatic breast cancer patients treated with palbociclib [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-11-07.