Cardiovascular toxicities in patients with triple negative breast cancer receiving treatment with chemotherapy and immunotherapy

Triple-negative breast cancer (TNBC) is an aggressive subtype accounting for ~15% of breast cancers. Data demonstrates improved survival using a combination of immune checkpoint inhibitors (ICIs) and chemotherapy. While anthracyclines and ICIs individually pose cardiovascular risks, data on their combined cardiotoxic effects are limited.

This ongoing prospective observational study monitors TNBC patients receiving curative-intent anthracyclines and ICIs using a standardized protocol (Figure 1). Surveillance includes clinical assessments, echocardiography, and cardiac biomarkers at predefined time points. We present preliminary data from the first 37 enrolled patients.

The mean ± SD age at diagnosis was 53 ± 13 years. Baseline comorbidities included hypertension (24.3%), dyslipidemia (35.1%), diabetes (10.8%), ischemic heart disease (5.4%), hypothyroidism (18.9%), and other autoimmune disease (5.4%). Five patients (13.5%) had prior cancer with anthracycline exposure.

Baseline echocardiograms showed normal LVEF (62.4±4.3%) and GLS (n=25) -19.8±2.5%. Baseline troponin levels (n=34) were all normal.

Twenty two patients (59.5%) completed the neoadjuvant regimen. Pembrolizumab was discontinued in 11 (29.7%) and doxorubicin in 5 (13.5) due to toxicities. Two (5.4%) patients declined anthracyclines, leading to concurrent pembrolizumab omission.

ICI-associated toxicities occurred in 17/37 (45.9%) patients including 2 (5.4%) cases of grade 1 myocarditis (confirmed by CMR). Other immune-related events included thyroiditis (n=5), hepatitis (n=3), dermatitis (n=2), adrenal insufficiency (n=2), hypophysitis (n=1), and sudden hearing loss (n=1). Eight patients received corticosteroids.

Post-anthracycline echocardiograms (available in n=32) showed 2D LVEF of 57.7± 4.2 (baseline 62.0±4.2%), with asymptomatic CTRCD in 8/32 (25%) patients (mild CTRCD in 6 and moderate in 2), and an elevated high-sensitivity troponin (>99th percentile) in 14/32 (43.8%).

Adjuvant pembrolizumab was initiated in 12/37 patients (32.4%). The main reasons for omission were prior ICI toxicity (21.6%), residual disease requiring alternative treatment (18.9%), and complete pathological response (16.2%). Three patients (25%) discontinued adjuvant pembrolizumab due to non-cardiovascular ICI-related toxicity.

In this preliminary report of a cohort study of women with TNBC receiving ICIs and anthracyclines, cardiovascular events were common and included myocarditis in 5.4%, abnormal troponin in 43.8%, and CTRCD in 25% (mostly mild). These findings may be due to prospective surveillance identifying low-grade (asymptomatic) myocarditis/injury and/or a chance finding due to small sample size. Our preliminary findings highlight the need for continued monitoring and larger studies to better understand cardiovascular risks in patients receiving a combination of ICIs and anthracyclines.