Correlation of FOXA1 expression with Oncotype Dx recurrence scores

Abstract

11058 Background: Oncotype Dx assay (ODX) is a diagnostic assay that predicts the benefit of chemotherapy and assesses the likelihood of breast cancer (BC) recurrence in patients with estrogen receptor (ER) positive BC. The forkhead-box A1 (FOXA1) transcription factor is linked to ER regulated gene transcription and its expression is associated with ER positive luminal A type BC. Since higher FOXA1 expression is associated with ER positive luminal A BC, we investigated whether FOXA1 expression levels show a correlation with ODX recurrence scores in BC patients. Methods: 120 cases of BC from IU and affiliated hospitals had ODX performed on tumor blocks. 78 patient tumor blocks with ODX recurrence score have been analyzed for FOXA1 using IHC. FOXA1 expression was measured using intensity X percentage scoring. The correlation of FOXA1 scores and ODX recurrence scores with each other and with other variables was examined. Other variables included age, progesterone receptor (PR) status, tumor size, grade, histological type, and race. All p values are two-sided and have been adjusted for multiple comparisons using Bonferroni-Holm's method. Results: Twenty-one of 78 cases analyzed were < 50 years. ODX recurrence scores were low, intermediate, and high in 55.1%, 32.1%, and 12.8% of cases, respectively. Ductal carcinomas accounted for 73.1% of tumors, while 11.5% were lobular. Fifty percent of tumors were histologic grade II, 37% and 13% were grade I and III, respectively. PR was negative in 9 cases. Caucasians accounted for 78.2% of cases vs 7.7% African-Americans. FOXA1 expression correlated negatively with ODX recurrence score (p=.003), and histologic type (p=.024). ODX recurrence score also correlated negatively with PR (p=.034) with 78% of the PR negative cases having a high or intermediate ODX score. The correlation between FOXA1 expression and ODX recurrence score remained significant after adjusting for multiple comparisons and controlling for confounders such as histological type, grade, and PR. Conclusions: We demonstrate that FOXA1 expression has an inverse correlation with ODX recurrence scores. FOXA1 expression can potentially be used as a prognostic marker in low risk ER positive BC patients who lack access to ODX assays. This observation needs to be confirmed with a larger sample size. No significant financial relationships to disclose.