Abstract P1-08-35: Androgen receptor expression and changes in serum dehydroepiandrosterone sulfate levels in locally advanced breast cancer patients who received neoadjuvant chemotherapy

Abstract

Abstract Purpose: The associations between androgen receptor (AR) expression, serum dehydroepiandrosterone-sulfate (DHEA-S) level and response to neoadjuvant chemotherapy (NCT) were investigated in locally advanced breast cancer patients who received NCT. Methods: Between May 2008 and April 2013, a total of 346 patients underwent NCT mainly based on anthracycline with or without taxane regimens. Biomarkers including AR were immunohistochemically determined using biopsy specimens before NCT and tumors with ≥ 1% nuclear staining were considered positive for AR. Changes in serum DHEA-S levels before and after NCT were examined by chemiluminescent immunoassay (Access DHEA-S, Beckman Coulter, Inc., Brea, CA) in 205 (59.2%) patients. Pathologic complete response (pCR) was defined as the absence of residual invasive carcinomas in the surgical specimens of breast and lymph nodes. Breast cancer subtypes were categorized by immunohistochemistry of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Results: Mean age at diagnosis was 49.7 years (range, 26–76). Clinical tumor size was ≥ 2cm in 243 (70.2%) patients and 318 (91.9%) showed node-positive disease at initial presentation. AR-positive tumor was determined in 195 (56.4%) patients and 95 (27.5%) achieved pCR after NCT. AR-negative tumors were significantly associated with grade III, ER-negative, PR-negative, HER2-negative, high Ki-67 index, and triple-negative subtype tumors. By univariate logistic regression analysis, AR-negative tumor showed significantly higher odds ratio of 1.650 (95% CI, 1.026–2.654; p-value, 0.039) for achievement of pCR. Nevertheless, not AR status but breast cancer subtype, longer duration of NCT and use of targeted agents remained to be significant for pCR by multivariate model. In the analysis of subgroup by breast cancer subtypes, AR-negative tumor was associated with pCR in 75 patients with the low proliferative luminal A subtype, while AR-positive tumor achieved higher pCR in 59 patients with the HER2-positive luminal B subtype. In 205 patients available for serum DHEA-S levels, there was no difference in DHEA-S between pCR and non-pCR groups, although a trend of decrease in DHEA-S after NCT was noted among postmenopausal AR-positive or luminal A subtype women who achieved pCR. Conclusions: AR expression might predict pCR in locally advanced breast cancer patients who undergo NCT, but this implication could be different according to breast cancer subtypes. Clinical significance of changes in serum DHEA-S levels during NCT remains to be elucidated. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-35.