Abstract S3-5: Discordance in Hormone Receptor and HER2 Status in Breast Cancer during Tumor Progression

Abstract

Abstract Background: In the metastatic situation therapy management is routinely based on primary tumor estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Alterations in these therapy predictive factors may lead to altered management. Methods: Breast cancer patients in the Stockholm health care region who relapsed from 1997 through 2007 were included and intra-individual primary tumor and relapse ER status, PR status and HER2 status accessed. Biochemical, immunohistochemical (IHC) or immunocytochemical (ICC) methods were used for determination of ER and PR (cut-off value of 0.05 fmol/µg DNA and 10%), respectively. For HER2, primary tumors were investigated using IHC with two or three monoclonal antibodies, confirmed by Fluorescence In Situ Hybridization (FISH) for IHC 2+ and 3+ and recurrences using ICC or FISH. The pathology laboratory at Karolinska University Hospital have continuously participated in quality assurance programs for hormonal receptor and HER2 analysis. Results: In 477, 447, and 108 patients, ER, PR and HER2 information was assessed from both primary tumor and relapse. Intra-individual primary tumor and relapse information for ER, PR and HER2 was available in 68 patients. ER and PR status changed in 26% and 35% from positive in primary tumor to negative in relapse tumor, and 7% and 6% changed from negative to positive, respectively. In 11 (10%) patients, tumors changed HER2 status, seven patients (7%) changed from HER2 positive to HER2 negative and 4 patients (4%) from HER2 negative to HER2 positive. Univariate analyses showed a significantly (log rank P<0.0005) differential survival in women related to intra-individual primary and relapse ER and PR status, respectively. In addition, a significant two-fold increased risk of dying in ER positive women changing to ER negative, compared to stable ER positive women, was noted using a multivariable proportional hazard model. Conclusions: More than every third patient changed ER and PR status and one patient in ten changed HER2 status during tumor progression. Intra-individual primary and relapse ER and PR status was significantly associated with differential survival in women. In addition, patients loosing ER had an almost two-fold increased risk of dying compared to concordant ER positive patients. Thus, altered management through tumor progression may improve survival and implies the need for hormonal receptor and HER2 investigations in metastatic lesions. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S3-5.