Abstract P3-04-12: Pathological and molecular effects of lack of PR expression in ER positive breast tumors

Abstract

Abstract Background: Evaluation of hormone receptor status is standard in breast cancer diagnosis; however, prognosis and treatment decisions are frequently based on the status of the estrogen receptor (ER) but not the progesterone receptor (PR). To determine how PR status affects etiology and outcome of ER positive tumors, pathological and molecular characteristics of ER+PR+ and ER+PR- tumors were assessed. Methods: ER and PR positivity were defined as >10% staining and all patients with ER+PR+ and ER+PR- were identified. Differences in pathological characteristics were evaluated using Chi-square tests with P<0.05 defining significance. RNA was isolated from primary tumor cells after laser-microdissection and hybridized to U133A 2.0 arrays. Gene expression data was analyzed by ANOVA using a false-detection rate <0.5 and >2.0-fold difference to define significance. Results: Of the 1,139 ER+ tumors, 21% were PR-. Age at diagnosis, ethnicity, tumor size, lymph node and Ki67 status did not differ between groups; however, patients with PR- tumors were significantly more likely to be diagnosed at an advanced stage, with high-grade, HER2 positive tumors, and more likely to die of disease. Thirty genes were differentially expressed including significantly higher expression levels of APOBEC3B and significantly lower expression of GREB1, MAPT and SCUBE2. Discussion: Expression of PR significantly alters tumor biology and clinical outcomes of ER positive tumors. Genes with altered expression in PR negative tumors are associated with more aggressive characteristics, such as increased invasion, kataegis, regulation of ER and response to tamoxifen. Thus, PR status is critical in the diagnosis and treatment of patients with ER positive breast tumors. Citation Format: Rachel E Ellsworth, Allyson L Valente, Matthew T Hueman, Craig D Shriver. Pathological and molecular effects of lack of PR expression in ER positive breast tumors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-12.