Background / Purpose: Breast cancer mortality in the United States falls unevenly across racial and ethnic lines. Black women have a 38% higher breast cancer mortality rate than White women despite a 5% lower incidence, and they carry significantly higher prevalence of type 2 diabetes (T2D) and obesity, comorbidities that interact syndemically with breast cancer to worsen outcomes. Federally-funded clinical trials shape the evidence base for breast cancer care, yet the extent to which they account for these metabolic comorbidities in trial design has not been systematically examined.
Methods: We conducted a retrospective analysis of 90 completed NIH- and other federal agency-funded female breast cancer clinical trials registered on ClinicalTrials.gov as of July 2023. Three parallel evaluation methods were applied: systematic review of inclusion and exclusion criteria; pharmacologic analysis of FDA-labeled and off-label drug indications for every intervention, conducted by credentialed pharmacology team members; and AI-assisted keyword recognition across protocol texts, with human adjudication. Trials were stratified into pharmacological and device interventions (n=72) and behavioral interventions (n=18).
Results: Fewer than 15% of trials explicitly addressed T2D in eligibility criteria; only one trial explicitly addressed obesity. Approximately 75% made no mention of diabetes, and over 90% made no mention of obesity. Only five trials considered both comorbidities together. Behavioral interventions targeting diet, exercise, and weight management failed almost universally to screen for or stratify by metabolic status.
Implications: Federally-funded breast cancer research remains predominantly reductionist in design, overlooking the metabolic and syndemic realities that shape outcomes for Black women, Latina, South Asian, and Native Hawaiian and Pacific Islander women. Future NIH funding should prioritize trial designs that integrate metabolic comorbidities into eligibility, stratification, and analytic frameworks to advance equity in cancer research.
