Purpose Previous reports suggest that radiation therapy for breast cancer (BC) can cause ischemic heart disease, with the radiation-related risk increasing linearly with mean whole heart dose (MWHD). This study aimed to validate these findings in younger BC patients and to investigate additional risk factors for radiation-related myocardial infarction (MI). Methods and Materials A nested case-control study was conducted within a cohort of BC survivors treated during 1970 to 2009. Cases were 183 patients with MI as their first heart disease after BC. One control per case was selected and matched on age and BC diagnosis date. Information on treatment and cardiovascular risk factors was abstracted from medical and radiation charts. Cardiac doses were estimated for each woman by reconstructing her regimen using modern 3-dimensional computed tomography planning on a typical patient computed tomography scan. Results Median age at BC of cases and controls was 50.2 years (interquartile range, 45.7-54.7). Median time to MI was 13.6 years (interquartile range, 9.9-18.1). Median MWHD was 8.9 Gy (range, 0.3-35.2 Gy). MI rate increased linearly with increasing MWHD (excess rate ratio [ERR] per Gy, 6.4%; 95% confidence interval, 1.3%-16.0%). Patients receiving ≥20 Gy MWHD had a 3.4-fold (95% confidence interval, 1.5-7.6) higher MI rate than unirradiated patients. ERRs were higher for younger women, with borderline significance (ERR <45years , 24.2%/Gy; ERR ≥50years , 2.5%/Gy; P interaction = .054). Whole heart dose-volume parameters did not modify the dose-response relationship significantly. Conclusions MI rate after radiation for BC increases linearly with MWHD. Reductions in MWHD are expected to contribute to better cardiovascular health of BC survivors.

Women treated with anthracycline-based chemotherapy and IMC irradiation (in an older era) with considerable mean heart dose exposure have substantially increased incidence of several CVDs. Screening may be appropriate for some BC patient groups.

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Aims Anthracyclines increase heart failure (HF) risk, but the long‐term prevalence of myocardial dysfunction in young breast cancer (BC) survivors is unknown. Early measures of left ventricular myocardial dysfunction are needed to identify BC patients at risk of symptomatic HF. Methods and results Within an established cohort, we studied markers for myocardial dysfunction among 569 women, who were 5–7 years (n = 277) or 10–12 years (n = 292) after BC treatment at ages 40–50 years. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed by echocardiography. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) was measured in serum. Associations between patient‐related and treatment‐related risk factors and myocardial dysfunction were evaluated using linear and logistic regression. Median ages at BC diagnosis and cardiac assessment were 46.7 and 55.5 years, respectively. Anthracycline‐treated patients (n = 313), compared to the no‐anthracycline group (n = 256), more often had decreased LVEF (10% vs. 4%), impaired GLS (34% vs. 27%) and elevated NT‐proBNP (23% vs. 8%). GLS and LVEF declined in a linear fashion with increasing cumulative anthracycline dose (GLS: +0.23 and LVEF: −0.40 per cycle of 60 mg/m2; P < 0.001) and GLS was worse for patients with left breast irradiation. The risk of NT‐proBNP >125 ng/L was highest for patients who received 241–300 mg/m2 anthracycline dose compared to the no‐anthracycline group (odds ratio: 3.30, 95% confidence interval: 1.83–5.96). Conclusion Impaired GLS and increased NT‐proBNP levels are present in a substantial proportion of young BC survivors treated with anthracyclines. Whether this will lead to future cardiac disease needs to be evaluated by longitudinal assessment.