HER2/neu Status on Pre and Post Neoadjuvant Chemotherapy
S Nofech-Mozes, W Hanna. Sunnybrook Health Sciences Centre, Toronto, Canada
Background: Neoadjuvant chemotherapy is administered in locally advanced breast cancer and in some cases of resectable cancers. The selection of chemotherapeutic agents and Trastuzumab in this setting is based on the expression of biological markers tested on core needle biopsies (CNB). In this study, we examined the possible effect of neoadjuvant treatment on the expression of HER2/neu by assessing the concordance between HER2/neu tested prior and following treatment.
Design: We assessed HER2/neu status on breast core biopsies in a cohort of 53 cases registered at the Odette Cancer Centre in the locally advanced breast cancer clinic before treatment was initiated. All CNB were evaluated for HER2/neu oncoprotein overexpression using immunohistochemistry (IHC) and gene amplification using florescence in situ hybridization (FISH). The subsequent resection specimens were evaluated by IHC and equivocal cases were assessed by FISH. The neoadjuvant regimen in these patients included anthracycline based chemotherapy (doxorubicin or epirubicin) and in patients with ER/PR negative tumors taxanes (paclitaxel, docetaxel). None of the patients received neoadjuvant trastuzumab.
Results: In 45/53 cases HER2/neu status was available on the resection specimens (5 cases had no residual tumor, 2 cases had the resection in another hospital and 1 case progressed and remained unresectable). CNB were HER2/neu positive in 14/45 (31.1%) cases by IHC and in 15/45 (33.3%) by FISH. Resection specimens were HER2/neu positive in 12/45 (26.7%). Overall IHC-CNB correlated with IHC-resection in 39/45 (86.6%). There were 6 discordant cases: 4 IHC-CNB positive/IHC-resection negative and 2 IHC-CNB negative/IHC-resection positive. Of note, 3/4 IHC-CNB positive/IHC-resection negative cases were FISH negative and the fourth case demonstrated low level of amplification. Overall FISH-CNB correlated with IHC-resection in 41/45 (91.1%). There were 4 discordant cases, all FISH-CNB positive/IHC-resection negative. Two of 4 discordant cases demonstrated low level of amplification.
Conclusions: This group of aggressive breast cancer shows a relatively high percentage of HER2/neu positivity (30%). There is a high level of concordance of HER2/neu status on CNB and tumors post neoadjuvant treatment. We observed a change in HER2/neu status in about 10% of the cases post chemotherapy which may be a result of chemotherapy effect or tumor heterogeneity. Retesting residual tumor for HER2/neu post treatment is therefore recommended in this setting.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 45, Tuesday Morning