Abstract PD8-04: Racial differences in the molecular landscape of breast cancer

Abstract

Abstract Background:African Americans (AA) have a higher mortality associated with breast cancer (BC) when compared to Caucasians (CC).This has been attributed to diverse factors that include access to care, reproductive factors and different somatic genomic profiles. We aimed to compare the racial mutational landscape of 565 BC samples. Methods:DNA from formalin-fixed paraffin-embedded samples was sequenced using the Illumina NextSeq (Agilent SureSelect XT, 592 gene selected based on COSMIC database) and MiSeq (TruSeq, 47 gene) for mutation and gene amplification analyses. Protein expression was evaluated by Immunohistochemistry (IHC). The exome aggregation consortium database was assessed for known ethnicity associations. Results:Tumor samples from 118 AA and 447 CC female patients were included in this analysis. AA were younger (median age 56 vs58y, p0.005) and had higher proportion of triple negative BC (TNBC) (32% vs17%, p0.001). 50.3% of the samples were obtained from primary tumors and the remainder from metastatic sites. This was similar in AA and CC (48.8% vs51.8% primary tumors, pNS). The two genes with highest mutation prevalence were TP53 and PIK3CA. AA had fewer PIK3CA mutations (14.7% vs28.2%, p0.03). Within HR+/HER2+ and HR+/HER2- subtypes there was a similar trend in the number of PIK3CA mutations but it was no longer significant. The remainder mutation analysis did not differ between races. In terms of protein expression there were significant differences in the androgen receptor(AR), RRM1, EGFR and TS expression (table). AR positivity defined as ≥10% was less frequent in AA (40.0% vs60.4%, p0.0001 and when adjusted for age, p0.005) and associated with PIK3CA mutations in both AA and CC (p0.01 and p0.007). AR expression in TNBC was positive in 17.8% of CC and 5.4% of AA (pNS). Copy number variation (CNV) data assessed by NextGen revealed significantly higher gene copy number in AA compared to CC in CCND1 (16% vs4%, p0.04), FGF19 (16% vs1.3%, p0.01) and FGF4 (16% vs3%, p0.02). When only TNBC was considered, RRM1, TOPO1 and TUBB3 expression was significantly higher in AA than CC (table) and there were no differences in the mutational analyses. Evaluation of other BC subtypes (HER2, HR positive) is currently underway. Conclusions:In this large cohort of AA who underwent genomic profiling there were relatively few differences in the mutation analysis compared to CC. The only significant difference seen was the lower number of PIK3CA mutations in AA, which had been previously reported in a cohort of 105 AA from the TCGA data (Keenan et al. JCO 2015). Protein expression by IHC revealed lower expression of AR in AA, even after adjustment for age, which could have therapeutic implications. Some of the racial differences found in the molecular landscape of BC including PIK3CA mutations, AR, EGFR expression and CNV may contribute to a more aggressive tumor biology in AA. Protein expression by IHCBCTNBCAA %CC %pAA %CC %pHER2/neu912ns00nsAR40600.005180.07ER44620.0000nsPR35460.0900nsEGFR30160.036050nsERCC133460.063626nsMGMT6163ns6571nsPD-150340.066548nsPD-L106ns011nsPGP76ns1015nsPTEN5658ns4247nsRRM139270.0459270.01TLE350590.104357nsTOP2A7164ns86470.08TOPO16358ns69460.03TS44300.016349nsTUBB355410.0677510.03 Citation Format: Lynce F, Xiu J, Nunes MR, Swain SM, Gatalica Z, Isaacs C, Pohlmann P. Racial differences in the molecular landscape of breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD8-04.