Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

Treatment of triple-negative invasive breast cancers, defined by the absence of estrogen and progesterone receptors and c-erbB2 expression, remains challenging. Androgen receptor, a member of the nuclear receptor superfamily that is involved in signaling pathways regulating cell proliferation, has been implicated in breast tumorigenesis. We immunohistochemically examined the expression of androgen receptor, basal markers (CK14, 34 beta E12) and EGFR in 699 triple-negative invasive breast cancers in tissue microarrays using the streptavidin-biotin method, and correlated the findings with clinical outcome. Positive androgen receptor expression was defined as staining of 1% or more of tumor cell nuclei. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. Cox proportional hazards models were used to determine the effect of androgen receptor on survival outcomes. Immunohistochemical positivity was observed in 38% of tumors, with the proportion of stained tumor cells ranging from 1 to 95% (mean 29%, median 10%). Androgen receptor expression was inversely associated with histologic grade and mitotic score. CK14, 34 beta E12 and EGFR confirmed 85% of cases to be basal-like, without significant association of basal-like phenotype with androgen receptor expression. Disease-free survival was significantly better in androgen receptor-positive triple-negative breast cancer, with a trend for improved overall survival. Decreased recurrence likelihood in both triple-negative and basal-like tumors (hazard ratio, 0.704; 95% confidence intervals, 0.498-0.994; P=0.0464; and hazard ratio, 0.675; 95% confidence intervals, 0.468-0.974; P=0.0355, respectively) was noted within 5 years of diagnosis but not thereafter. Our study suggests that loss of androgen receptor in triple-negative breast cancers augurs a worse prognosis, including those with basal-like features. More work in elucidating its relationship with mechanisms of progression, as well as trials of targeted treatment for androgen receptor-expressing triple-negative tumors, needs to be performed.