P1-06-26: The EndoPredict Score Is a Response Predictor for Neoadjuvant Chemotherapy in ER-Positive, HER2−Negative Breast Cancer.

Abstract

Abstract Background: The EndoPredict (EP) score is a multigene classifier to predict the likelihood of distant recurrence in ER-positive, HER2−negative breast cancer patients treated with adjuvant endocrine therapy. Two large randomized phase III trials involving endocrine therapy only (n > 1700) demonstrated additional prognostic information of the EP score independent from clinicopathological parameters by classifying 49% as low risk. However, the predictive role of the EP is not clear. Therefore, we examined whether the EP Score also predicts sensitivity towards neoadjuvant chemotherapy in ER-positive, HER2−negative breast cancer patients. Methods: Four publicly available gene expression data sets (Affymetrix HG-U133A) were retrieved from the gene expression omnibus (GEO) data repository. All analyzed breast cancer patients were treated with anthracycline or taxane/anthracycline-based neoadjuvant chemotherapy. Microarray cel files were MAS5 normalized with a global scaling procedure and a target intensity of 500. The analysis was restricted to ER-positive, HER2−negative breast cancer patients according to pre-specified cut-off levels for the respective ESR1/ERBB2 Affymetrix probesets. The EP score was calculated and patients were classified as having low or high risk according to the pre-specified validated cut-off value. Pathological complete response (pCR) — defined as no residual invasive cancer in the breast or lymph nodes — was used as the primary endpoint for the assessment of treatment response. Results: The EP Score was examined in 221 ER-positive, HER2−negative breast cancer patients treated with neoadjuvant therapy. Among the 221 patients, 61 tumors (27.6%) were classified as EP-low-risk, whereas 160 tumors (72.4%) were EP-high-risk. Only one of the EP-low-risk tumors achieved a pCR after neoadjuvant therapy, whereas 24 of the 25 pCR events were classified as EP high risk. The sensitivity of the EP score was 96% and the negative predictive value 98% with an area under the receiver operating characteristic curve of 0.73. Conclusions: The EP Score is a predictor of chemosensitivity in the neoadjuvant setting. The test correctly identified all but one of the patients achieving a pCR suggesting that the benefit of cytotoxic chemotherapy is limited to the EP high risk group. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-26.