Increasing Survivors of Anthracycline-related Cardiomyopathy with Breast Cancer in Trastuzumab Era: Thirty-one-Year Trends in a Japanese Community

Abstract BACKGROUND Trastuzumab has improved breast cancer (BC) prognosis and reduced anthracycline use. However, the characteristic changes of anthracycline-related cardiomyopathy (ARCM) in patients with BC remain unclear. We sought to update our knowledge of ARCM in the trastuzumab era. METHODS This was a retrospective observational cohort study. A total of 2,959 patients with BC treated with anthracyclines in three regional cancer centers in Niigata City between 1990 and 2020 were included. Seventy-five patients (2.5%) developed ARCM and were categorized into two groups: pre- 2007 (early phase) and post- 2007 (late phase), corresponding to before and during the trastuzumab era in Japan. RESULTS The incidence of ARCM peaked at 6% in the 1990s, decreased, and remained at 2% until the 2010s. Mean anthracycline use in the early and late phases was 525 mg/m2 and 307 mg/m2 (P<0.001), and the 5-year survival rates were 28% and 45% (P=0.058), respectively. Human epidermal growth factor receptor type 2 (HER2) positivity with trastuzumab therapy in late phase was an independent predictor for mortality within 10 years (hazard ratio =0.24, 95% confidence interval: 0.10–0.56; P=0.001). At the end of the late phase, there were four times as many patients with ARCM as at the end of the early phase (twenty-six and six, respectively). Survivors of BC increased more rapidly in the late phase, though the rate of accumulation change was slight in the anthracycline-treated BC group and more pronounced in the ARCM group (P <0.001). CONCLUSIONS With increasing survivor with ARCM in the trastuzumab era, subtypes of HER2 positivity have gained significant importance in treating patients with ARCM in BC.