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, 34βE12) 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, 34βE12 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.