Methodological and molecular factors underlying racial disparities in cancer outcomes

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Project Summary/Abstract Despite improvements in cancer survival, racial disparities have persisted for both men and women. Although overall incidence is lower among Black women than White women, mortality is greater; in contrast Black men have both greater incidence and mortality. Breast and ovarian cancers, which both contribute to the incongruity among women, are hormonally-driven cancers with overlapping genetic, molecular, and lifestyle risk factors. In 2020, breast cancer was the cause of over 40,000 deaths, while ovarian cancer accounted for nearly 15,000. Deaths attributable to these cancers occur disproportionately among Black women. Disparities in mortality are most pronounced among patients initially diagnosed with non-metastatic disease. Among these patients, cancer recurrence is a necessary precursor to a cancer-specific death. However, recurrence is poorly understood due to the lack of systematically-collected population-based data. Current estimates of recurrence risk are based on clinical trial data, clinic-based registries, or algorithms using administrative claims, and therefore are not representative of all patients, particularly those with less access to specialized trials or clinics. Accurate population-based estimation of recurrence is critical to fully understand mortality disparities. An important methodological consideration in population-based estimation is the follow-up of cancer survivors years after initial diagnosis. Previous studies have suggested racial minority patients are more likely to be lost to follow-up, biasing race-specific estimates. Aim 1 of this project will investigate how differences in loss to follow-up bias race-specific, population-based recurrence estimates, using the rich resources of the Georgia Cancer Registry (GCR), a population-based registry in a large, racially diverse state. The GCR is the first population-based cancer registry to systematically identify and register recurrences among breast cancer survivors. Aims 2 and 3 will use existing epidemiologic studies to investigate patient-level drivers underlying the disparities. Aim 2 will investigate the association between androgen receptor in tumor cells and breast cancer recurrence among premenopausal women, particularly those with aggressive subtypes that do not respond to available endocrine therapy and that are more commonly diagnosed in Black women. Aim 3 will investigate the role of menopausal hormone treatment, and the mediating effects of this exposure on treatment factors, in ovarian cancer progression, an association that has only been examined in White women. Results from this research will provide a framework for accurate estimation of population-based recurrence rates, additional insight into factors contributing to racial disparities in breast and ovarian cancer outcomes, and will inform future studies aimed at reducing inequities. In addition, the fellowship will provide a rich array of epidemiologic training, research, and career development that will contribute to the candidate’s ability to be a successful and independent cancer researcher, with knowledge and skills in a broad array of epidemiologic methods, familiarity with the clinical underpinnings of cancer care, and understanding of cancer disparities.