Triple negative breast cancers are a heterogeneous group of
tumors characterized by poor patient survival and lack of targeted
therapeutics.
Androgen receptor has been associated with
triple negative breast cancer pathogenesis, but its role in the different subtypes has not been clearly defined. We examined
androgen receptor protein expression by immunohistochemical analysis in 678 breast
cancers, including 396 triple negative
cancers. Fifty matched
lymph node metastases were also examined. Association of expression status with clinical (race, survival) and pathological (basal, non-basal subtype, stage, grade) features was also evaluated. In 160
triple negative breast cancers,
mRNA microarray expression profiling was performed, and differences according to
androgen receptor status were analyzed. In triple negative
cancers the percentage of
androgen receptor positive cases was lower (24.8% vs 81.6% of non-triple negative cases), especially in African American women (16.7% vs 25.5% of
cancers of white women). No significant difference in
androgen receptor expression was observed in primary
tumors vs matched metastatic lesions. Positive
androgen receptor immunoreactivity was inversely correlated with
tumor grade (p<0.01) and associated with better overall patient survival (pā=ā0.032) in the non-basal triple negative
cancer group. In the microarray study, expression of three genes (HER4, TNFSF10, CDK6) showed significant deregulation in association with
androgen receptor status; eg CDK6, a novel therapeutic target in triple negative
cancers, showed significantly higher expression level in
androgen receptor negative cases (p<0.01). These findings confirm the prognostic impact of
androgen receptor expression in non-basal
triple negative breast cancers, and suggest targeting of new
androgen receptor-related molecular pathways in patients with these
cancers.