Relationship between Molecular Phenotype of Invasive Breast Cancer and Expression of Androgen Receptor
K Cole, R Tamimi, R Hu, G Colditz, S Schnitt, L Collins. Beth Israel Deaconess Medical Center, Boston; Harvard Medical School, Boston; Harvard School of Public Health, Boston; Brigham and Women's Hospital, Boston; Washington University School of Medicine, St. Louis
Background: Distinct subsets of invasive breast cancer have been identified by their patterns of gene expression and include luminal (A and B), HER2 and basal-like types. While prior studies have demonstrated that androgen receptor (AR) is expressed in many breast cancers, the frequency of AR expression in relation to the various breast cancer subtypes defined by molecular analysis has not been previously studied in detail.
Design: We constructed tissue microarrays (TMAs) from paraffin blocks of 3,093 breast cancers that developed in women enrolled in the Nurses' Health Study between 1976-1996. TMA sections were immunostained for ER, PR, HER2, CK5/6 and EGFR. Results of these stains were used to categorize each cancer as luminal A (ER+ and/or PR+ and HER2-); luminal B (ER+ and/or PR+ and HER2+); HER2 (ER- and PR- and HER2+); basal-like (ER-, PR-, HER2- and EGFR or CK5/6+); or unclassified (negative for all markers). TMA sections were also immunostained with a monoclonal antibody to AR. The relationships between AR expression and molecular subtypes were analyzed.
Results: There were 1,990 invasive cancers with complete immunophenotypic data: 73% were luminal A, 5% luminal B, 6% HER2, 11% basal-like and 5% unclassified. Overall, 77% of cases were AR-positive but the frequency of AR expression differed significantly across the molecular phenotypes (p<0.0001). AR expression was commonly observed in luminal A and luminal B cancers (88% and 72% of cases, respectively), but was less frequently seen in HER2 cancers (60% of cases). Moreover, despite being defined by the absence of ER and PR expression and being considered as hormonally unresponsive, 32% of basal-like cancers showed expression of AR.
Conclusions: AR expression is most commonly seen in the luminal A- and B-types of invasive breast cancer. However, expression of AR is also seen in approximately one-third of basal-like cancers, despite the absence of ER and PR expression. This observation provides further evidence that basal-like cancers represent a heterogeneous group. In addition, it raises the possibility that targeting the AR pathway may represent a novel therapeutic approach to the management of patients with basal-like cancers, a group for whom the identification of therapeutic targets is an important clinical goal.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 23, Monday Morning