Androgen Receptor (AR) Expression in Ductal Carcinoma In Situ (DCIS) and Its Relationship to Molecular Subtype
K Cole, R Tamimi, R Hu, G Colditz, S Schnitt, L Collins. Beth Israel Deaconess Medical Center, Boston, MA; Harvard Medical School, Boston, MA; Harvard School of Public Health, Boston, MA; Brigham and Women's Hospital, Boston, MA; Washington University School of Medicine, St. Louis, MO
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. Recent studies have also identified the same molecular subtypes in DCIS, albeit with different frequencies than in invasive cancers. Prior studies have demonstrated that AR is expressed in many invasive breast cancers and in DCIS. However, the frequency of AR expression in relation to the subtypes of DCIS 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 invasive cancers and DCIS 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 of DCIS were analyzed.
Results: There were 228 DCIS with complete immunophenotypic data: 65% were luminal A, 13% luminal B, 13% HER2, 7% basal-like and 2% unclassified. Overall, 85% of DCIS cases were AR-positive but the frequency of AR expression differed significantly across the molecular phenotypes (p=0.002). AR expression was commonly observed in DCIS with luminal A and luminal B phenotypes (91% and 83% of cases, respectively), but was less frequently seen in the HER2 subtype (77% of cases). Moreover, despite their being defined by absence of ER and PR expression, 69% of basal-like DCIS showed expression of AR.
Conclusions: Among DCIS cases, AR expression is most often seen in luminal A and B phenotypes. However, expression of AR is also seen in approximately two-thirds of basal-like DCIS, despite the absence of ER and PR expression. This observation raises the possibility that targeting the AR pathway may represent a novel approach to the prevention of breast cancer in patients at increased risk for the development of basal-like breast cancers.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 26, Tuesday Morning