TNBC: A DISCRIMINATORY DISEASE
TNBC discriminates against women of African heritage. Although some of the things that seem to predispose women of African ancestry to this form of breast cancer are socioeconomic and lifestyle factors, they do not completely explain the disparity, suggesting that genetic ancestry is linked to etiology. Understanding this heritability is therefore essential to advancing knowledge of TNBC biology.
Some studies report that half of all Nigerian women and ~50–80% of Ghanaian women with breast cancer have TNBC. Other studies document TNBC incidence in certain sub-Saharan African countries as similar to those found in black US or UK breast cancer patients.
Some studies of Northern African countries report a TNBC incidence of <20% of all breast cancers, indicating that locoregional African ancestry may matter for risk of TNBC.
About 20–45% of African American women with breast cancer have TNBC. This incidence is about 2–3 times greater than the incidence of TNBC in European American or British women.
WHAT HAVE GENES GOT TO DO WITH IT?
There are some things all women can do to reduce their risk of breast cancer, like maintaining a healthy body mass index. But even taking modifiable risks into account, TNBC is still unusually more common in women of African origin than other ancestral groups. This suggests a genetic, ancestry-based component to TNBC rates. Indeed, a few molecular aberrations have been identified among African American women, such as a greater proportion of P53 mutations, and basal-like expression signatures, but more findings of this nature are needed. How then to translate these findings into clinical practice worldwide is the next, open question.
WHERE DO WE GO FROM HERE?
There are many possible avenues to explore in TNBC research, which is why ICART was established: to facilitate international collaborations to achieve more together. One next step might be to identify prognostic and predictive biomarkers that are both cheap and easy to discern in TNBC patients of all racial and ethnic groups, although this need is particularly urgent for TNBC patients of African ancestry. High-resolution ancestry mapping is also needed to fully elucidate the risk factors related to biogeographic heritage; this is especially important given varying degrees of genomic admixture around the world. Broader genome-wide association studies (GWAS) involving samples from admixed populations will help to diversify the data pools from which we extrapolate meaning. Remarkably, ~90% of samples used in GWAS to date have been European American, a highly homogeneous group in terms of global ancestry that composes only ~3.5% of the world’s population.