Patterns in circulating microRNA in black (B) versus white (W) patients with triple-negative (TN) breast cancer (BC).

Abstract

1046 Background: Breast cancer is by far more common in W than in B women. Black women have more aggressive disease that occurs almost a decade earlier, it is usually triple negative and has a lower survival. Objectives to determine 1) if plasma miRNA expression differs between B and W women, and 2) if variation in miRs may explain the observed survival difference in TNBC in W compared to B women. Methods: We determined miRNA profiles in plasma collected before removal of breast tumors in three groups of W and B women: 1) normal controls (N), 2) TN and 2) ER/PR positive BC. Expression miRNA profiling of 754 miRNAs on the ABI Open Array detected 101miRNAs in plasma. We compared miRNA expression in cancer patients and race-matched controls. A moderated t-statistic through the R/Bioconductor 'limma' was used to compare the mean response between subject factors of interest. Results with a p<0.05 were considered statistically significant. Characteristics: 32 patients were included in this analysis (mean age 50 years; range 31-68), 10 had stage III TNBC (5 B & 5 W); 10 had stage III ER/PR+BC (5 B, 5 W); and 12 were controls (6 B, 6 W) Results: W TNBC patients overexpressed (15 fold higher than normal) 20 miRs in plasma (let-7d, let7g, miR-103, -10a, 15a, -9, -99b, -181a, -18a, -502, -187, -365 and others), these miRs were not found in any of the B patients. Six microRNAs (such as miR-34a, -127 and others) were 15 fold higher than normal controls in B cancer patients, these miRs were not detected in W patients with TNBC. Four miRs in B and 8 miRs in W were not previously reported in association with breast cancer suggesting that they may be connected to the host response. Conclusions: The striking difference in the patterns of plasma miRNA expression between B and W patients may provide the key to the large difference in outcome between these groups when receiving similar treatments, the worse prognosis group may carry the miRs that promote metastasis. The seed-soil hypothesis may explain the better prognosis in W patients. W women may carry those miRNAs that support an “exaggerated” response to systemic treatment, while the B may have the miRs that favour metastasis.