Abstract P3-12-06: Biomarkers of Malignant Potential in Breast Tissue in Relation to Short-Term Breast Cancer Risk

Abstract

Abstract Background: Biomarkers expressed in benign or normal breast tissue may be important indicators of subsequent risk of malignancy, but investigations identifying such have been few. Limited previous evidence suggests that loss of expression of several breast cancer tumor markers in benign tissue, relative to normal tissue, may contribute to malignant progression. We examined expression of markers implicated in tumorigenesis among women who developed breast cancer shortly after benign biopsy. Material and Methods: We conducted a nested case-control study within a population-based cohort of 15,000 women who received benign breast biopsies between 1996 and 2005 in six New Mexico counties. We identified 95 women who developed breast cancer within 5 years of biopsy, and matched them to 3 similar controls who did not develop cancer. Benign breast as well as adjacent normal tissue was assayed using immunohistochemistry for epithelial and stromal markers plausibly related to risk of cancer development. Logistic regression models were employed to estimate odds ratios and 95% confidence intervals for breast cancer risk after adjustment for age, race/ethnicity, and risk category of benign biopsy. Results: Women who expressed estrogen receptor alpha in their normal tissue (10% or greater staining) had a 2.9-fold increased breast cancer risk (95% confidence interval (CI) 1.0-8.3). Those who expressed Cytokeratin 5/6 (Odds ratio (OR) 3.3; 95% CI 1.2-8.8) or Her2/neu (30% or greater staining) (OR 8.2; 95% CI 0.9-70.6) in normal tissue also appeared to have an elevated breast cancer risk, relative to those with expression below the threshold. In contrast, the presence of these markers in benign tissue was unrelated to subsequent development of breast cancer. Estrogen receptor staining of 10% or greater in normal tissue, but absence of staining in benign tissue, was not a risk factor for progression to breast malignancy (OR 4.9; 95% CI 0.7-34.8) Discussion: Our results suggest that biomarker expression in normal breast tissue may be an important component of risk assessment among women whoreceive benign breast biopsies. Findings such as these aim to identify women at highest risk for breast cancer development, allowing for the implementation of more frequent follow-up and new targeted interventions, while classifying most women as at low risk, providing reassurance and reducing the need for chemoprevention. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-06.