P4-02-12: Plasma Estradiol Levels and Degree of Estrogen Receptor Positivity by Image Analysis in a Large Cohort of Breast Cancer Cases: Results from the Nurses' Health Study.

Abstract

Abstract Background Breast cancer risk is strongly associated with endogenous reproductive hormones. There is also good evidence to suggest that endogenous estradiol levels are more strongly associated with the development of estrogen receptor (ER) positive breast cancers than with ER negative cancers. However, the degree of ER positivity in those cancers that develop is not yet established. Therefore, we sought to evaluate the proportion and intensity of tumor cells demonstrating ER positivity using image analysis in a large cohort of breast cancers for which we also had plasma estradiol levels. Design: Tissue microarray (TMA) sections of breast cancers from women enrolled in the Nurses’ Health Study were immunostained for ER (1D5, Dako Corporation, Carpinteria, CA). Slides were then scanned using the ScanScope slide scanning system (Aperio Technologies Inc., Vista, CA) and ER staining was assessed for both intensity and percent of nuclei staining positively using a specific algorithm, Nuclear v9, which evaluates nuclear size, intensity, roundness, curvature, compactness, and elongation. Plasma samples were collected prior to the date of diagnosis for all women in the study and estradiol levels were determined by radioimmunoassay following extraction and celite column chromatography. Result: Image analysis data for ER was available for 691 breast cancers. The mean percent of tumor cell positivity was approximately uniformly distributed, with a mean of 44.5%, (median=41.3%, max=99.6%). The proportion of tumor cells staining for ER from the TMA cores was positively associated with patient age (p<0.0001), and postmenopausal status (p=0.008), while inversely associated with tumor grade (p<0.0001). Among women with image analysis data for ER, plasma estradiol data were also available for 320 postmenopausal women. Estrogen receptor positivity (by proportion or intensity) did not vary according to plasma estradiol levels (p=0.17). Conclusion: While high concentrations of plasma estradiol are more strongly associated with the development of estrogen receptor positive breast cancer versus estrogen receptor negative cancers, the degree of estrogen receptor positivity in the breast cancers that develop is not influenced by this variable. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-12.