Cardiotoxicity screening of long-term, breast cancer survivors-The CAROLE (Cardiac-Related Oncologic Late Effects) Study

Abstract

Background: Long-term breast cancer survivors are at risk for cardiotoxicity after treatment, but there is insufficient evidence to provide long-term (~10 years) cardiovascular disease (CVD) screening recommendations. We sought to evaluate a tri-modality CVD screening approach.

Methods: This single-arm, feasibility study enrolled 201 breast cancer patients treated ≥6 years prior without CVD at diagnosis. Patients were sub-grouped: cardiotoxic (left-sided) radiation (RT), cardiotoxic (anthracycline-based) chemotherapy, both cardiotoxic chemotherapy and RT, and neither cardiotoxic treatment. Patients underwent electrocardiogram (EKG), transthoracic echocardiogram with strain (TTE with GLS), and coronary artery calcium computed tomography (CAC CT). The primary endpoint was preclinical or clinical CVD.

Results: Median age was 50 (29-65) at diagnosis and 63 (37-77) at imaging; median interval was 11.5 years (6.7-14.5). Among sub-groups, 44% had no cardiotoxic treatment, 31.5% had cardiotoxic RT, 16% had cardiotoxic chemotherapy, and 8.5% had both. Overall, 77.6% showed preclinical and/or clinical CVD and 51.5% showed clinical CVD. Per modality, rates of any CVD and clinical CVD were, respectively: 27.1%/10.0% on EKG, 50.0%/25.3% on TTE with GLS, and 50.8%/45.8% on CAC CT. No statistical difference was seen among the treatment subgroups (NS, χ² test, p = 0.58/p = 0.15).

Conclusion: This study identified a high incidence of CVD in heterogenous long-term breast cancer survivors, most >10 years post-treatment. Over half had clinical CVD findings warranting follow-up and/or intervention. Each imaging test independently contributed to the detection rate. This provides early evidence that long-term cardiac screening may be of value to a wider group of breast cancer survivors than previously recognized.

Keywords: breast cancer; cardiotoxicity; radiation; screening; survivorship.

FIGURE 1

Preclinical and/or clinical disease detected per each imaging modality alone and by combined modalities among all breast cancer survivors. (%)

FIGURE 2

Rates of preclinical and clinical cardiac disease among treatment sub‐groups

FIGURE 3

Cardiac disease incidence in treatment subgroups as found on each imaging modality. Abbreviations: CAC CT, coronary artery calcium scan; Cardiotox Chemo, cardiotoxic chemotherapy; Cardiotox RT, cardiotoxic radiation; EKG, electrocardiogram; No Cardiotox, no cardiotoxic chemotherapy or radiation; TTE w GLS, transthoracic echocardiogram with global longitudinal strain

FIGURE 4

Summary of clinical findings from EKG, TTE, and CAC CT among all participants and treatment subgroups