Impact of expression levels of mRNA HER2 and ESR1 on the pathologic complete remission (pCR) rate after neoadjuvant treatment with anthracycline-taxane containing chemotherapy in combination with trastuzumab in the GeparQuattro trial.

523 Background: Recent data suggest that benefit from (neo)adjuvant trastuzumab might be related to expression of HER2 and estrogen receptor (ESR1). We investigated mRNA levels of HER2 and ESR1 in core biopsies in HER2 positive tumors of the GeparQuattro trial and compared it to response to neoadjuvant treatment. Methods: In the GeparQuattro trial 445 HER2+ pts were included based on local testing and received neoadjuvant trastuzumab and chemotherapy (either 4 x EC →4 x docetaxel (D) or 4 x EC → 4 x D/capecitabine (C) or 4 x EC →4x D →4 X C). In 217 available pretherapeutic core biopsies HER2 levels were analysed by IHC, SISH and quantitative RT-PCR using predefined cutoffs; pCR was defined as ypT0is;ypN0. Results: Only 73% of the tumors (158 of 217) were centrally HER2 positive (cHER2+) by IHC/SISH, while 59 tumors (27%) were centrally HER2 negative (cHER2-). As all pts had received neoadjuvant trastuzumab, this gave us the possibility to evaluate response of HER2- tumors to trastuzumab. The pCR rate of ...