Genetics May Explain Aggressive Breast Tumors in African Americans
According to the results of a genomic analysis, several genetic characteristics linked with aggressive cancer are more common in the breast tumors of African American women compared to their white counterparts.
According to the results of a genomic analysis, several genetic characteristics linked with aggressive cancer are more common in the breast tumors of African American women compared to their white counterparts, according to the results of a study published in the Journal of Clinical Oncology.
To compare the genomic architecture of stage I/II breast cancers, Tanya Keenan, MD, of the Massachusetts General Hospital in Boston, and colleagues performed exome sequencing on 663 breast tumor samples from white women and 105 samples from African American women. They also conducted gene expression analysis on an additional 711 samples from white women and 159 samples from African American women.
Intratumor heterogeneity was greater among the samples from African American women compared to those from white women, including in cases of triple-negative breast cancer (TNBC).
“The greater genomic diversity within African American tumors suggests a greater capacity for clonal evolution that may contribute to aggressive or therapy-resistant disease,” wrote the study authors.
The African American women also had more basal tumors (39% vs 18.6%; P < .001) and fewer luminal A tumors as analyzed by a microarray prediction method (17% vs 34.7%; P < .001).
The top five genes most commonly mutated were the same in each group-TP53, PI3KCA, GATA3, CDH1, and MLLT3. But the top two genes (TP53 and PI3KCA) had different racial patterns. African American women had a greater frequency of TP53 mutations (42.9% vs 27.6%; P = .003) and fewer PI3K mutations (20% vs 33.9%, P = .008).
African American women also had a higher risk of tumor recurrence compared to their white counterparts (hazard ratio, 2.22). According to the study authors, TP53 mutations and the higher frequency of TNBCs influenced this racial difference in tumor recurrence.
From prior studies, it is known that African American women are more likely to die from breast cancer compared to white women-40% more likely, according to the Centers for Disease Control.
While the racial disparity is partly due to socioeconomic factors including access to care and income, prior studies have suggested that these issues cannot fully explain the differences in breast cancer outcomes. African American women tend to be diagnosed more frequently with a more aggressive form of breast cancer-TNBC-yet the genetic differences among tumors in these two populations had not been well characterized prior to the current study.
The analyses of the current study “suggest that poor breast cancer outcome in African American women may be driven not only by a greater burden of TNBC but also by genomic profile differences that make TNBCs in African Americans more aggressive than TNBCs in whites. These results highlight the critical need for research investigating the underlying pathogenesis and exploiting therapeutically the distinct biology of basal-like TNBC,” concluded the study authors.
