This review examines tumor biology, genetics, physical and lifestyle variables, hormone metabolism, and therapeutic obstacles that contribute to African American women’s increased rate of triple-negative breast cancer. It emphasizes the need for more research and better oncology care for African American women.
Triple-negative breast cancer (TNBC) is an aggressive subtype that accounts for 20% of breast cancers. Evidence suggests that African American (AA) women have higher rates of TNBC than White women. The mortality rate among AA women is also higher than that of other ethnic groups in the US. Moreover, AA women are typically diagnosed at an advanced cancer stage. A study published in the Georgetown Medical Review has explored the various biological and non-biological factors underlying this health disparity.
Physiological Mechanisms:
- Â Â Â Â Tumor Biology
TNBC lacks expression for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (ERBB2).
- Â Â Â Â Genetics
Among AA women from genetically predisposed families, one in four has an increased risk of BRCA mutations, and 20.4% of AA women with TNBC have a BRCA1 germline mutation. Upregulation of genes in the Wnt signaling pathway was observed in AA women with TNBC, which was associated with a shorter recurrence. Research concerning variation in mutations in AA breast cancer patients revealed that the genes PDE4D and FBXL22 were significantly associated with ER-negative breast cancer and found a higher prevalence of TP53, PIK3, and MLL3 mutations in White women. There are also specific differences in the tumor microenvironment of AA patients compared to TNBC patients of other ethnic groups.
- Â Â Â Â Physical and Lifestyle Factors
Obesity rates are high among AA people due to socioeconomic and various other factors. A study found that the prevalence of TNBC in AA obese women was 29% compared to 8.6% in non-obese women.
A balanced diet significantly reduces breast cancer-related mortality, whereas a high-fat diet increases tumor lethality. Physical activity is potentially inversely related to breast cancer incidence and recurrence. Increased physical activity is associated with a decreased incidence of ER-negative/PR-negative cancer compared with ER-positive.
- Â Â Â Â Hormone Metabolism
TNBC is highly anaerobic and glucose-dependent. There is evidence that glycolysis can be stopped in TNBC cell lines that have been treated with 3-bromo-2-oxopropionate-1-propyl ester.
Upregulation of androgen activation or expression can lead to tumorigenesis. Early onset of androgen receptor-positive TNBC can be associated with higher serum estrogen and androgen levels in premenopausal women. Prolonged use of estrogen-containing oral contraceptives is significantly related to the development of ER-negative cancers like TNBC in AA women.
- Â Â Â Â Treatment
TNBC has a lower pathologic response rate and often requires neoadjuvant therapy due to its advanced tumor grade. Health inequity due to low socioeconomic status leads to adverse outcomes. There is a disparity in insurance rates between AA and White American individuals, with rates at 11.9% and 8.2%, respectively. There is limited access to quality oncology care in impoverished areas. AA women are more likely to experience inappropriate therapy. Moreover, most therapeutic trials for TNBC fail to represent high-risk AA women.
Source:
Albert, T. (2023). The Physiological Mechanisms of Triple Negative Breast Cancer in African American Women. Georgetown Medical Review. https://doi.org/10.52504/001c.57753Â