Racial/Ethnic Disparities in Breast Cancer Risk: Genomics Meets Metabolomics

Although breast cancer is by far the most common cancer among all women worldwide, its incidence rates vary substantially in different populations. In the United States, rates are highest among white women, followed by African American (AA) and Hispanic American (HA) women. Among HA women, breast cancer incidence rates are higher among those born in the United States than among first-generation immigrants, who, in turn, have higher rates than their counterparts in their countries of origin. Among foreign-born HA women, breast cancer risk has been shown to increase with the duration of U.S. residency, degree of acculturation, and younger age at migration, underscoring the importance of environmental influence on breast cancer risk. On the other hand, overall breast cancer risk among HA women has been shown to increase with the degree of European contribution to their genetic admixture. Among AA women, a higher proportion of European ancestry has been associated with a less aggressive form of breast cancer (estrogen receptor [ER] positive/progesterone receptor [PR] positive and localized). These observations highlight the need for understanding the population genetic substructure in the evaluation of racial/ ethnic disparities in breast cancer incidence and prognosis. Although breast cancer is more likely to occur in white women, AA and HA breast cancer patients are more likely to die of their disease. The age at onset tends to be earlier in AA and HA women, and these cases tend to have more aggressive histologic characteristics, including the triplenegative breast cancer (TNBC) that lacks expression of ER, PR, and human epidermal growth factor receptor 2 (HER2). Interestingly, limited evidence suggests that TNBC is also overrepresented among Hispanic and African women in their countries of origin. The predisposition to more aggressive tumors likely has contributed to the higher mortality rates among young minority women. However, the poor prognosis of breast cancer among AA and HA women has also been attributed, in part, to inadequate health insurance, limited access to mammography, advanced disease stage at diagnosis, delayed and inadequate treatment, and a high prevalence of comorbidity.