Salganik, Max

Abstract Background: HR+ breast cancer in younger vs older patients may have distinct biological features. The Breast Cancer Index (BCI) is a gene expression-based assay that includes two component biomarkers: the HoxB13/IL17BR (H/I ratio), an endocrine response biomarker; and the molecular grade index (MGI), a set of proliferation-related genes. The objective of this study was to assess age-related associations with endocrine sensitivity (H/I), proliferative status (MGI), and quantitative expression of ER and PR. Methods: Data were extracted from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database containing clinicopathologic and molecular variables from clinical cases submitted for BCI testing. Molecular results from H/I, MGI, and quantitative (qPCR–based) ER and PR were analyzed across age groups. Chi-squared tests and ANOVA were used to compare the results between age groups (<40y, 40-49y, 50-59y, 60-69y, and ≥70y). Results: Analyses included 19,126 patients (median age at diagnosis 58.6y; 4.5% <40y, 20.6% 40-49y, 28.9% 50-59y, 32.5% 60-69y, and 13.6% ≥70y). Proliferation status (MGI) was significantly higher in patients <40y and 40-49y compared to older groups (P<.0001).H/I analysis indicated a similar distribution of high versus low endocrine responsiveness across all groups (P=.94), except the 40-49y group, in which fewer patients had high H/I (44.2% in <40y, 39.4% in 40-49y, 43.7% in 50-59y, 43.7% in 60-69y, and 43.1% in ≥70y; P=.0001). Median qER increased with age (P<0.0001), while qPR was similar across all age groups except for the 40-49y group (P=.57), in which expression was higher (P<.0001). Conclusion: Results from >19,000 patients with early-stage HR+ breast cancer and BCI testing showed a broad distribution in all variables. Tumors from the youngest patients (<40y) had the highest expression of proliferative genes and the lowest quantitative ER expression. However, endocrine response, according to the H/I biomarker, does not appear to be strongly linked to age. Citation Format: Melisko M, Chien AJ, Poage GM, Salganik M, Schnabel CA, Ruddy KJ, Blackwell K. Gene expression patterns in younger versus older HR+ breast cancer patients: An age-related analysis of HoxB13/IL17BR (H/I), proliferation status, and quantitative hormone receptor expression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-03.