The prognostic and predictive value of the androgen receptor (AR) in triple negative breast cancers (TNBC) remains controversial. We assessed the impact of AR in TNBC on core needle biopsy (CNB) and remaining tissue after neo-adjuvant chemotherapy (NACT) by menopausal status which affects the androgen/estrogens relation and pathological complete response (pCR) rate.
We retrospectively evaluated all consecutive TNBC patients receiving NACT between 2000 and 2017 treated in a single center with sufficient remaining diagnostic CNB material. AR-expression was assessed by immunohistochemistry using the ≥1% as per recommendation of ASCO/CAP guidelines for estrogen receptor. AR was correlated with baseline demographics and clinic-pathological characteristics, including stromal tumor infiltrating lymphocytes (sTILs), pCR (pT0-is, N0), AR-expression in remaining tumor, and metastasis for outcome using the Fine and Gray model for statistical analysis. We explored whether results differ by menopausal status.
71 women were eligible (median age 51.0 yrs; 35 postmenopausal), 6.7 yrs median follow-up. AR-pos was seen in 32%. pCR, reported in 39.8% (45.7% in pre- and 33.3% in postmenopausal) predicted metastasis; 3.5% if pCR; 37.3% if no-pCR. AR on CNB did not correlate with age, menopausal status, BMI, sTILs or pCR. AR-status on CNB was not associated with metastasis. 14% of 43 patients with no-pCR following NACT were AR-pos; this predicted a poor outcome. The difference in median TTM by AR was 4m longer if AR-pos but this was not significant. A total AR-score for proportion of cancer cells staining ≥34% was more frequently observed in postmenopausal patients (27%), as compared to the premenopausal ones (5.7%). This discrepancy might possibly explain the 12.3% higher pCR rate in premenopausal patients. % pCR by AR-expression (cut-off ≥1%) and menopausal status.
% pCR All % Premenopausal % Postmenopausal % All patients 39.4 45.7 33.3 AR-neg 39.6 41.6 37.5 AR-pos 39.1 54.5 25.0
AR-expression in TNBC does not affect pCR nor DDFS but was associated in our series with lower pCR in postmenopausal women. AR in residual TNBC following NACT predicted a worse outcome.
University Hospitals Leuven.
Funds of Friends for Cancer Research Leuven.
A. Smeets: Research grant to the institution: Merck, MSD Belgium. H. Wildiers: Personal: travel support: Roche, Pfizer; Institution: Consulting fees, Honoraria: Roche, AstraZeneca, Amgen, Lilly, Novartis, AbbVie, Vifor Pharma, Pfizer, Celldex therapeutics, Janssen-Cilag TRM Oncology, Puma Biotechnology, Orion Corp.; Research grant: Roche. P. Neven: Speaker’s fees, consulting fees, research support: Roche (all provided to his institute); Advisory board: Novartis, AstraZeneca, Lilly, Pfizer (all consulting fees are provided to his institute). All other authors have declared no conflicts of interest.