Transcriptional expression of Bcl-2 as predictive of response to neoadjuvant chemotherapy with trastuzumab in HER2-positive ER-positive breast cancer patients.

602 Background: Several trials have confirmed that pathologic complete response (pCR) rates after neoadjuvant chemotherapy (NAC) are significantly lower in HER2+/ER+ patients (pts) than in HER2+/ER− pts. To elucidate this phenomenon, we investigated the association of anti-apoptotic Bcl-2, which is frequently overexpressed in ER+ tumors, with to NAC resistance. Methods: Pretreatment formalin-fixed tumor tissues were collected from 75 HER2+ pts receiving NAC comprising anthracyclines, taxanes, and trastuzumab. mRNA expression was detected by PCR amplificationand quantitative primer extension using MassARRAY (Sequenom, CA). The panel of 15 genes comprised EGFR, HER2, HER3, IGF1R, FGFR, PTEN, INPP4B, SRC-1, DUSP4, ESR1, PgR, FOXA1, PDL1, CTLA-4, and Bcl-2, whose expressions were dichotomized according to median values. PIK3CA mutations were detected using MassARRAY genotyping. ER, PTEN, and Bcl-2 protein expressions were scored from 0 to 3 according to the frequency and intensity by immunohistochemisty (IHC)...