HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process

Abstract

BACKGROUND The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process. METHODS HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post‐CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2–T4,N1–N2 breast carcinoma and were treated by preoperative anthracycline‐based CT and then underwent surgery. The second group included 44 patients with metastatic breast carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2 status was determined by immunohistochemistry using an anti‐p185^HER/neu monoclonal antibody and was classified as overexpressed or not overexpressed. RESULTS Among the patients who received preoperative CT, HER2 overexpression was observed in 15 of 59 patients (25%). A complete pathologic response was observed in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining residual tumors and was no longer detectable in 2 tumors. In addition, the 29 tumors with no HER2 overexpression before CT remained negative after treatment. In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two patients who had low levels of HER2 overexpression in their primary tumors, no staining was observed in the secondary tumor (one pulmonary tumor and one liver tumor). There were no tumors in which the overexpression of HER2 was found only in the metastasis. CONCLUSIONS The current study showed that, in most patients, HER2 overexpression was unchanged after CT and in metastatic sites. No HER2 negative primary tumors became HER2 positive after patients received CT or during the metastatic process. In a few patients, a diminution in the level of HER2 expression was observed after CT or in secondary tumors. This may have been due to a transitory state of altered tumor cells or to the selection of HER2 negative tumor cells clones. Cancer 2002;94:2169–73. © 2002 American Cancer Society. DOI 10.1002/cncr.10456