A balancing act: racial disparities in cardiovascular disease mortality among women diagnosed with breast cancer

Background: The cardiotoxic effects of breast cancer therapies are well documented in clinical trials. However, clinical trials often underrepresent those at highest risk for cardiovascular disease (CVD)related outcomes and have limited generalizability to the larger breast cancer population. In addition, racial differences in treatment-associated CVD mortality have yet to be explored. In this study, we sought to quantify the relationship between breast cancer therapies and CVD mortality, and explore whether this effect differed between non-Hispanic black (NHB) and white (NHW) women.

Methods: Using data from the Georgia Cancer Registry, we identified women diagnosed with a first primary invasive breast cancer [2010-2014], residing in the metropolitan Atlanta area (n=3,580 NHB; n=4,923 NHW), and followed them for mortality through December 31, 2018. Exposures of interest included therapies with potential cardiotoxic effects including chemotherapy and hormone therapy, which are routinely collected by the GCR. Individual agents are not captured within the GCR, therefore trastuzumab was identified using natural language processing of textual descriptions. We used propensity score weighted Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between each treatment modality and CVD mortality among the overall cohort and by race.

Results: In the overall cohort, similar hazards of CVD mortality were found among women treated with chemotherapy (HR =1.10, 95% CI: 0.62, 1.96) and hormone therapy (HR =0.94, 95% CI: 0.59, 1.50), compared to women who did not receive the respective treatments. In contrast, women treated with trastuzumab had a higher hazard of CVD mortality compared to women not treated with trastuzumab (HR =2.05, 95% CI: 0.76, 5.52). In race-specific models, hormone therapy was associated with a higher hazard of CVD mortality among NHB women (HR =2.18, 95% CI: 0.78, 6.12), but not NHW women (HR =0.66, 95% CI: 0.39, 1.13). Similar, albeit attenuated, associations were found for chemotherapy. We were unable to investigate race-specific effects of trastuzumab due to low prevalence and insufficient number of events.

Conclusions: In our study, we observed more pronounced associations of chemotherapy and hormone therapy with CVD mortality among NHB women, for whom we know have greater CVD-related comorbidities at breast cancer diagnosis. Patients may benefit from treatment plans that find a balance between curative breast cancer treatment and prevention of CVD-related events and mortality. CVD-related outcomes may be most relevant for women with hormone receptor positive disease due to shared risk factors (e.g., obesity, tobacco use, physical activity) and longer survival.

Keywords: Breast neoplasms; cardiotoxicity; cardiovascular diseases; health disparities; mortality.