HER2 evaluation process for neoadjuvant targeted therapies in breast cancer.

Abstract

3034 Background: Treatment with a combination of HER2-targeted therapies has emerged as an addition of trastuzumab to neoadjuvant chemotherapy regimens in breast cancer patients and it goes on increasing. For clinical HER2 determination, immunohistochemical (IHC) analysis is an attractive method and all IHC 2+ cases are categorized as equivocal and should be reflexed to fluorescence in situ hybridization (FISH) testing. However, research in recent years with respect to false-negative cases for HER2 testing have been reported, and it comes to the question of what considering the indication for trastuzumab in the neoadjuvant chemotherapy. To clarify these controversial points in applying the results of HER2 testing in the clinical setting, we performed a retrospective analysis of core needle biopsy (CNB) and surgical specimen results. Methods: 422 patients underwent primary operations for early breast cancer at Tokyo-West Tokushukai Hospital (Tokyo, Japan) from October 2008 to December 2012. Among these patients, 262 patients who received CNB prior to operation were enrolled. Those patients who received preoperative chemotherapy or had DCIS were excluded. With regard to diagnostic criteria, HER2 positivity was defined as either 3+ by IHC or FISH analysis amplification ratio of ≥2.2. In addition, if in any cases which CNB samples or surgical specimens showed HER2-positive had defined true HER2-positive cases, we assessed the false-negative results of the HER2 test via IHC using CNB samples and surgical specimens. Results: In a matched cohort of 262 patients, 59 cases showed HER2-positive (five cases were CNBs negative to surgical specimens positive, 14 cases were CNBs positive to surgical specimens negative, and 40 cases were both positive). If we decide for selection of trastuzumab target cases by CNBs only, we make mistakes in indications of trastuzumab for five (8.5%) of 59 HER2-positive cases who were CNBs negative to surgical specimens positive. Conclusions: There are quite a few cases show false negatives for HER2 testing in CNB samples. In cases of considering the indication for trastuzumab in the neoadjuvant chemotherapy, even if the CNB samples resulted in negative, we consider that retesting with FISH analysis should be carried out.