Summary

Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences with Tumor Recurrence

Authors: Keenan T, Moy B, Mroz EA, et al.

Source: J Clinical Oncol. 2015;33:3621-3627.

www.jco.ascopubs.org/content/early/2015/09/14/JCO.2015.62.2126.abstract

Although advances in the treatment of breast cancer have substantially lowered the mortality rate for breast cancer, there is still a disparity in the mortality rate between African American women and white women. African American women are 40% more likely to die as a result of breast cancer than white women in the United States according to the Centers for Disease Control and Prevention (CDC). Many reasons for this disparity have been touted, including socioeconomic status and treatment differences. However, disparity still exists, even when statistics have been adjusted to take these factors into account. This suggests that there is an underlying biologic difference. Several studies have shown higher expression of dysregulated cell cycle genes and lower expression of cell adhesion genes in African Americans, but until this paper a correlation had not been drawn between tumor biology differences and disparate outcomes. While the actual endpoint of this paper is tumor recurrence, extrapolations for poorer prognosis and ultimately mortality can be inferred from a shorter time to recurrence.

The authors assessed differences in somatic mutations of genes in a cohort of primary breast cancers in 105 African American women and 663 white women obtained from the NCI Data Portal. There was a higher prevalence of TP53 mutations and intratumor heterogeneity in the African American set than white breast cancers. A higher prevalence of TNBC in the African American data set was also noted. In assessing tumor recurrence, the basal subset of the TNBC portended a shorter time to recurrence. This subset of cancers was significantly more prevalent in the African American population, and thus showed a higher recurrence rate in the African American population. The authors suggest that the greater intratumor heterogeneity of the African American breast tumors lends a greater capacity for clonal evolution that may contribute to more aggressive or therapy-resistant disease. Importantly, when adjusting for TNBC, TP53 mutation, and basal subtype, the racial differences in tumor recurrence were attenuated. This suggests that the disparity in recurrence may be attributed in part to the higher prevalence of TNBC and basal-like tumors in African Americans.

In conclusion, tumors of African American women had greater genetic heterogeneity and a larger burden of the TNBC and basal subtype. The racial disparity in breast cancer outcomes between African American women and white women may be attributed in part by these genomic profile differences. There is still yet more work to be done to elucidate these complex associations.