Clinical Implications of Intra-Tumoral Variation in HER2 Expression in Breast Cancer
M Bonham, A Lal, S Devries, E Hwang, J Rabban, F Waldman, Y Chen. UCSF, San Francisco, CA
Background: HER2 is overexpressed in 20% of invasive breast carcinomas. Previous studies have shown that HER2 status is similar between in situ and invasive components of the same tumor and that there is high concordance for HER2 expression between primary breast cancer and its corresponding metastases. Little is known about the intratumoral variation of HER2 status in breast cancer. This study examines the intratumoral heterogeneity of HER2 and explores the possible clonal evolution of this phenotype.
Design: We reviewed a database of 893 primary breast cancer cases from 2005-2008 and found 11 cases of breast cancer with at least two distinct patterns of differing intensity in HER2 expression by immunohistochemisty. The intratumoral variation in HER2 among the 11 cases was examined by FISH (Vysis) and CISH (Zymed) analysis. The presence of clonal relationship between the variable regions of HER2 expression will be assessed by array comparative genomic hybridization (aCGH).
Results: Ten of the 11 cases showed markedly different levels of HER2 expression among invasive and in situ components within the same tumor. Four invasive ductal carcinomas had two distinct levels of HER2 expression. Six in situ carcinomas showed different levels of HER2 expression. FISH confirmed the amplification status and difference in expression among the eleven samples. CISH morphologically correlated the variation in gene amplification to the histopathology. The clonal relationship and evolution of these lesions with different HER2 will evaluated by aCGH.
HER Heterogeneity in Components of Breast Cancer+,- indicates HER2 status. All cases are invasive ductal carcinoma with DCIS except cases 9 &10 which are invasive lobular carcinoma with LCIS. Metastasis in case #1 was HER2 neg.
Conclusions: Intratumoral variation in HER2 expression is a rare event. However, the possibility of HER2 variation is clinically significant in that treatment decisions are increasingly made based on HER2 studies after analysis of a limited sampling of tumor such as core needle biopsy, fine needle aspiration, or by molecular analysis of tumors that may contain both invasive and in situ components with distinct subpopulations. In some cases, the different areas of HER2 expression in invasive component appear to be derived from the in situ component, however, the cause for the HER2 expression change and potential effect on treatment outcome is unknown.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 43, Tuesday Morning