Cumulative incidence of chemotherapy-induced cardiotoxicity during a 2-year follow-up period in breast cancer patients

Breast Cancer Res Treat. 2020 Jul;182(2):333-343. doi: 10.1007/s10549-020-05703-5. Epub 2020 May 28.


Purpose: Cardiotoxicities are adverse effects often reported in chemotherapy-treated breast cancer patients. This study evaluated the potential risk factors and cumulative incidence of doxorubicin-induced cardiotoxicity in Korean breast cancer patients.

Methods: We retrospectively analyzed the data of 613 breast cancer patients who underwent a multigated acquisition (MUGA) scan or echocardiography prior to chemotherapy and at least one post-chemotherapy follow-up MUGA scan/echocardiography between 2007 and 2016 at National Cancer Center, Korea. The Cox proportional hazards models were used to evaluate cardiotoxicity risks. Competing risks analyses were performed to estimate cumulative incidence of cardiotoxicity.

Results: Risk factors associated with cardiotoxicity within 2 years of doxorubicin administration included age [adjusted hazard ratio (aHR) = 1.02, 95% confidence interval (CI) 1.00-1.04; p = 0.05], metastasis (aHR = 2.66; 95% CI 1.36-5.20; p < 0.01), and concomitant trastuzumab (aHR = 4.08; 95% CI 2.31-7.21; p < 0.01). The cumulative incidence of patients with cardiotoxicity was 6.1% at 2 years (without substantial change from about 9 months)and 20.2% at 2 years (without substantial change from about 15 months) after initiation of doxorubicin-containing therapy without and with trastuzumab, respectively.

Conclusions: Susceptibility to chemotherapy-induced cardiotoxicity within 2 years of doxorubicin initiation in breast cancer patients was elevated with old age, metastasis, and concomitant trastuzumab. Regular imaging monitoring at least up to 9 months after doxorubicin initiation in patients treated without concomitant trastuzumab, and 15 months in patients treated with concomitant trastuzumab, is needed for early detection of chemotherapy-induced cardiotoxicity.

Keywords: Breast cancer; Cardiotoxicity; Doxorubicin; Heart failure; Trastuzumab.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Breast Neoplasms / therapy*
  • Cardiotoxicity / diagnosis
  • Cardiotoxicity / epidemiology*
  • Cardiotoxicity / etiology
  • Chemoradiotherapy, Adjuvant / adverse effects
  • Chemoradiotherapy, Adjuvant / methods
  • Chemotherapy, Adjuvant / adverse effects
  • Chemotherapy, Adjuvant / methods
  • Dose-Response Relationship, Drug
  • Doxorubicin / adverse effects*
  • Echocardiography
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Mastectomy
  • Middle Aged
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Trastuzumab / adverse effects*


  • Doxorubicin
  • Trastuzumab