Patterns of elevated coronary artery calcium and diminished myocardial perfusion reserve in premenopausal women with early breast cancer

Background Coronary artery calcium (CAC) is associated with cardiovascular (CV) disease in middle and older age. Myocardial perfusion reserve (MPR) is a functional marker of preclinical perfusion deficits and predicts future CV events. Limited information is available on CAC and MPR in young women undergoing therapy for cancer who receive potentially cardiotoxic therapy and face possible CV risk from the cancer itself. Purpose To characterize the impact of treatment and disease factors on CV health in a population of young women with cancer, we examined the prevalence of CAC and MPR levels in premenopausal women undergoing therapy for breast cancer (BC). Methods The CROWN study seeks to understand the natural history of CV health in premenopausal women with Stage I-III BC. Baseline coronary computed tomography angiography (CCTA) and adenosine stress cardiac magnetic resonance (CMR) imaging are performed within 30 days of the completion of surgery, radiation and chemotherapy, if given. CAC and MPR were assessed by BC disease subtype (hormone receptor (HR)+ vs HR-) and by systemic therapy prior to enrollment (no chemotherapy, chemotherapy without an anthracycline (ANTH), ANTH-based chemotherapy without immune checkpoint inhibition (ICI) or ANTH+ICI). Patient characteristics are summarized by mean and SE for continuous variables and frequency/percentage for categorical variables. Mean MPR was summarized by therapy group and compared between ANTH+ICI versus all other therapies combined using a two-sample t-test. Presence of CAC (CAC>0) was compared between ANTH+ICI and all other therapies using Fisher’s exact test. Results 18/54 (33%) women with paired CCTA and CMR scans had CAC on CCTA [Table 1]. CAC, observed in all treatment groups, was highest with ANTH+ICI where 7/9 (78%) had CAC. ANTH+ICI patients were significantly more likely to have CAC than patients who did not receive ICI (p=0.004). The ANTH+ICI group also had markedly diminished MPR relative to the other treatment groups [Fig. 1, p=0.10], driven by the 7 women with CAC. CV risk factors were balanced between the CAC+ and CAC=0 groups, but numerically higher in the groups with diminished MPR, though numbers are small. Age was generally balanced among the groups, though the 2 women who received ANTH+ICI and did not have CAC were 8.7 years younger than the ANTH+ICI with CAC group (35.0±2.0 vs 43.7±3.3). Conclusion Rates of CAC in premenopausal women undergoing early BC care are markedly higher than that observed in comparably aged non-cancer cohorts and raise concern for possible future CV events in the cancer population. CAC in premenopausal women who have not yet received systemic therapy may suggest an association between BC and CV injury. Rates of CAC were highest with ANTH+ICI therapy and combination of ANTH+ICI with CAC was associated with diminished perfusion reserve in this young cohort, indicating CV toxicity related to ICI therapy.