In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 523-523
Abstract:
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 cHER2+ tumors was significantly increased (46.8%, p 〈 0.0005) compared to cHER2-, who had a pCR rate of only 20.3%. Similar results were obtained if HER2 positivity was determined by RT-PCR (pCR rate 50% vs. 17.4%, p 〈 0.0005). Assessment of HER2 status by RT-PCR showed a concordance of 86.2% with the IHC/SISH status. In uni- and multivariate logistic regression analysis of cHER2+ cases including continuous HER2 and ESR1 mRNA levels the HER2 mRNA expression was significantly associated with prediction for a pCR in (univ.: OR 1.43, 95% CI 1.11-1.83, p=0.005; multiv.: OR 1.42, 95% CI 1.11-1.83, p=0.006). In the cHER2+ tumors, the pCR rate was similar for ESR1 mRNA positive (47.4%) and ESR1 negative tumors (46.3%). Conclusions: Only pts with cHER2+ tumors independently of the method used have an additional benefit in terms of a pCR from adding trastuzumab to chemotherapy. In cHER2-negative patients the pCR rate is comparable to the pCR rate in the non trastuzumab treated population. Increasing HER2 mRNA levels were associated with a better response to trastuzumab based treatment in cHER2 + tumors.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.523
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
