Immunohistochemical Expression of Androgen Receptor in Triple Negative Breast Cancer: Significant Association with Improved Disease Free Survival
Aye Aye Thike, Luke Chong, Poh Yian Cheok, Jabed Iqbal, Puay Hoon Tan. Singapore General Hospital, Singapore, Singapore
Background: Triple negative (TN) invasive breast cancers are defined by the absence of estrogen receptor, progesterone receptor and c-erbB2 expression. Treatment of TN breast cancers remains challenging. Androgen receptor (AR) is a member of the nuclear receptor superfamily. It is known to be involved in signaling pathways that regulate cell proliferation and has been implicated in breast tumorigenesis. This study investigates the immunohistochemical expression of AR in a large series of triple negative invasive breast cancers diagnosed at our institution, correlating its expression with clinical outcome.
Design: The cohort comprised 699 invasive TN breast cancers diagnosed from 1994 to 2010 for which tissue microarrays were constructed. Antibodies to basal markers (CK14, 34βE12, EGFR) and AR were applied to sections cut from tissue microarray blocks, using the streptavidin-biotin method. Positive AR expression was defined as staining of 1% or more of invasive tumor cell nuclei. Disease free survival (DFS) and overall survival (OS) were defined as time from diagnosis to recurrence or death respectively, and correlated with protein immunohistochemical expression. A p value <0.05 defined statistical significance.
Results: AR expression was observed in 38% of tumors and the proportion of AR positive tumor cells ranged from 1% to 95% (mean 29, median 10). About 54% of tumors harbored AR immunoreactivity in more than 10% of tumor cells. AR immunoexpression was inversely associated with histologic grade (p=0.002) and mitotic score (p=0.009). Among 147 triple negative tumors in this series with known metastatic disease on follow-up, 67% of primary tumors did not exhibit AR immunoreactivity. CK14, 34βE12 and EGFR confirmed 85% of cases to be basal-like, without significant association of basal-like phenotype with AR expression. DFS was significantly better in AR positive TN breast cancer (p=0.05), with a trend observed for improved OS, as well as better DFS and OS, in AR positive basal-like TN breast cancers.
Conclusions: Our study demonstrated that loss of AR expression in invasive TN breast cancers was significantly associated with worse pathological parameters while its presence augured an improved prognosis. More work in elucidating the relationship of AR with mechanisms of progression, as well trials in harnessing the potential of targeted treatment for AR expressing TN tumors, need to be performed.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 5, Tuesday Morning