Do current family history-based genetic testing guidelines contribute to breast cancer health inequities?

Abstract

Prior to the recommended age for population-based breast cancer screening by mammography, which ranges from 40−50 years depending on guidelines, the main way to identify higher risk women for earlier breast cancer (BC) screening to improve outcomes and discuss targeted chemoprevention is through specific clinical guidelines which are largely based on family history of breast cancer and known mutations in breast cancer susceptibility genes. The annual percent change (APC) in early-onset BC continues to rise, with the higher early-onset cancer burden and mortality continuing to be seen in non-Hispanic black (NHB) women compared to non-Hispanic white (NHW) women. Coupled with the increasing incidence overall as well as the lower percent of BC family history reported in NHB women compared with that of NHW women means that continued reliance on guidelines to identify women for genetic screening and initiation of early BC screening based largely on family history could lead to even greater BC health inequities. The similarity in the prevalence of mutations in key BC susceptibility genes between NHB and NHW women contrasts sharply to the differences in age-specific incidence rates between NHB and NHW women, supporting that there must be environmental modifiers that are contributing to the increased incidence in NHB women. This reality further argues for identifying NHB women early in adulthood through genetic testing who may benefit from tailored BC risk-reduction programs and early BC screening.

BRCA germline mutations in multiethnic gynecologic patients: A 10-year retrospective analysis from a single cancer institute

“…It has been reported that testing restricted by personal or family history can lead to missing germline variant carriers [ 20 , 21 ]. Furthermore, testing guidelines are often family-history based and may disproportionately lead to underdiagnoses in some racial or ethnic populations [ 22 ]. While it’s tempting to adapt a universal panel-approach to avoid missing potential patients, the risks and health benefits of testing (e.g.…”

Evidence-Based Interventions for Reducing Breast Cancer Disparities: What Works and Where the Gaps Are?

“…NCI currently includes only two genomic susceptibility EBCCPs (one focused on breast cancer susceptibility and the other on colorectal cancer susceptibility), neither of which met our quality metrics, nor were they inclusive or multilevel. This is of concern for breast cancer disparities given that NHB women develop breast cancer earlier than NHW women, despite having similar prevalence of pathogenic mutations in key susceptibility genes and genomic susceptibility of one family member impacts the entire family [ 42 ].…”

Population‐based genetic testing for cancer susceptibility genes: quo vadis?

“…For Lynch syndrome, the Bethesda molecular criteria and Amsterdam‐II clinical criteria miss 12%–30% and 55%–70% of carriers, respectively 5 . Recent data show that traditional family history guidelines may further magnify health inequalities for minority communities like non‐Hispanic Black populations, by identifying proportionally fewer high‐risk women in these populations 12 . We showed that despite 25 years of a well‐structured national service for clinical genetics, free at the point of care, over 97% of BRCA carriers remain undetected in a population of 16 million in London 13 .…”

“… 5 Recent data show that traditional family history guidelines may further magnify health inequalities for minority communities like non‐Hispanic Black populations, by identifying proportionally fewer high‐risk women in these populations. 12 We showed that despite 25 years of a well‐structured national service for clinical genetics, free at the point of care, over 97% of BRCA carriers remain undetected in a population of 16 million in London. 13 Forecasting models suggest that current detection rates are inadequate, and even doubling the rates would take 165 years to identify the ‘clinically detectable’ proportion of BRCA carriers, with 50% remaining unidentifiable as they don't fulfil the testing criteria.…”