Abstract P5-10-13: Pre-surgical plasma microRNA pattern defines a biologically distinct triple negative breast cancer (TNBC) occuring in black (B) compared to white (W) women.
Authors: Shapira I , Lee A , Oswald M , Taioli E , Bradley T , Barginear M , Mason C , Keogh M , Budman D 
Published: August 2014

Background: Black women with triple negative breast cancer have 46% lower survival rates; this may be due to differences in tumor biology. We analyzed presurgical plasma microRNA of white (W) and black (B) women with TNBC enrolled in the breast ovarian tissue bank to detect if differences in the pre-surgical plasma microRNA could be detected in B patients relative to W patients relative to healthy controls.

Aims: MicroRNA in pre-surgical plasma of TNBC W or B was compared to plasma from controls race and age matched controls to assess if differences in plasma and tumor microRNA may explain the survival disparity observed in B. We addressed 2 questions 1) are the patterns in the pre-surgical miRNA profiles different between W and B patients, differences that could explain outcomes discrepancy? 2) What are the miRs changes in patients W or B relative to healthy controls?

Methods: Between 2004 and 2011 plasma miRNAs was measured before, after surgery, during and after chemotherapy in 73 surgical breast cancer patients and 11 age and race matched controls. We also analized miRs in the tumor and benign adjacent breast in 5 specimes. Samples were analyzed using qRT-PCR in the ABI's TaqMan OpenArray Panel for 750 miRs. Samples were spiked with ath-miR-159a and hsa-miR-320 most strongly correlated in its expression to ath-miR-159a through the Pearson correlation coefficient. 2-sample t-test was used for comparisons between means and ANOVA followed by post-hoc test to compare the mean response between subject factors of interest. All tests were 2-tailed; statistical significance was set at p &lt; 0.05.

Results: 44 W and 23 B, mean age at surgery 48 years (range 35–78) and 11 controls – mean age 44 years (range 35–67). Black TNBC patients did not express over 70 % of pre-surgical plasma miRs present in the W pre-surgical plasma. B over-expressed high levels of miR-1244, -190 and -638, which were not detected in any of the W patients (p &lt; 0.005). W patients and controls expressed miRs10a, -190, -502-3p, -548, and -9* not detected in B TNBC patients. White patients over-expressed over 80% of plasma miRs present in controls, while black patients over-expressed only 30% of miRs present in controls (P &lt; 0.005).

Conclusions: Patterns of pre-surgical miR expression are different in B versus W patients with TNBC. In B the presence of TNBC leads to silence in circulating plasma miRs in comparison to W and controls. In W the presence of the tumor increases the miR “chatter”. Black patients have a different “communication” style between host-TNBC when analyzed by the response of plasma microRNA. This difference may call for different treatment protocols for patients. Specific treatment interventions, such as administration of chemotherapy before surgery, in an attempt to increase the microRNA levels in plasma may improve the outcomes of black patients with TNBC.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-13.