Correlation between HER2 amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2 positive breast cancer.

Abstract

e12641 Background: HER2 targeted therapy in combination with chemotherapy have changed the aggressive natural history of HER2-positive tumors. To select patients to be treated with this type of agents, determination of HER2 status is usually carried out by immunohistochemistry, followed by in situ hybridization in equivocal cases (2+). There are contradictory data in literature regarding correlation between level of HER2 amplification determined by FISH and early and long-term treatment benefits. Objectives: The aim of this study was to correlate quantitative results of FISH (ratio HER2/CEN17 and number of HER2 signals/nucleus) with the grade of response to neoadjuvant treatment with trastuzumab and chemotherapy. Methods: We analyzed 100 consecutive cases of stage I-III breast carcinomas treated with trastuzumab and chemotherapy in the neoadjuvant setting at A Coruña University Hospital between 2005 and 2016. At Santiago University Hospital, 4 tissue microarrays were prepared and the IQFISH (Dako-Agilent) technique was performed using pretreatment biopsies. Results: HER2 amplification was found in 92 of 100 cases studied. Pathological Complete Response (pCR) (Miller-Payne grading system) was obtained in 58% of the patients whose tumors showed amplification. No pCR was obtained in the 8 patients whose tumors were negative by FISH (not amplified). Analysis of the quantitative results demonstrated a statistical significant direct correlation between pCR and both HER2/CEN17 ratios and HER2 gene copies/nucleus (p = 0.002 and p= 0.004, respectively). We also demonstrated an association between the HER2 amplification level (both ratios and numbers of HER2 signals) and a trend toward improved disease free survival (DFS) (p = 0.451 and p= 0.619, respectively). Conclusions: HER2 amplification level determined by FISH it is a good and available predictive factor of response and must be included in pathologic reports because it can provide valuable information to oncologists on the possibilities of achieving pCR after neoadjuvant treatment in HER2-positive breast cancer. Key words: Breast cancer, FISH, HER2 amplification, trastuzumab, neoadjuvant therapy, pathological complete response.