Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors

Heart. 2013 May;99(9):634-9. doi: 10.1136/heartjnl-2012-303151. Epub 2013 Jan 24.

Abstract

Objective: Although adjuvant trastuzumab improves survival in patients with HER2-positive early breast cancer, there is growing concern about the long-term effect of trastuzumab-induced cardiotoxicity (TIC). We retrospectively assessed the incidence of TIC and heart failure (HF) to identify possible risk and protective factors.

Design: Retrospective study.

Setting: Institute for Cancer Research and Treatment, Medical Oncology Department.

Patients: Consecutive patients who started adjuvant trastuzumab between 2007 and 2010.

Main outcome: Measures TIC was defined as an absolute left ventricular ejection fraction (LVEF) decrease ≥ 15 points from baseline or a LVEF<50%. Logistic regression was used to estimate OR and their 95% CI in order to evaluate the risk of TIC, considering potential cardiac risk factors (hypertension, hypercholesterolaemia, diabetes mellitus, smoke, cardiac ischaemia and previous chest radiotherapy) and protective factors (β-blockers, ACE inhibitors and/or angiotensin receptor blockers).

Results: Among 179 patients, 78 cases of TIC (44%, 95% CI 37% to 51%) and four cases of HF (2%, 95% CI 0% to 4%) were reported. 14 patients stopped trastuzumab as a result of TIC. None of the cardiac risk factors or concomitant cardiovascular medications altered the risk of TIC. A previous cumulative dose >240 mg/m(2) of doxorubicin or >500 mg/m(2) of epirubicin increased the risk of TIC compared with lower doses (OR 3.07; 95% CI 1.29 to 7.27, p=0.0011).

Conclusions: TIC is a frequent, albeit generally mild, adverse event in clinical practice. Further studies are warranted to better define the risk of and protective factors for TIC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Heart Diseases / chemically induced*
  • Heart Diseases / epidemiology
  • Humans
  • Incidence
  • Logistic Models
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Stroke Volume / drug effects
  • Trastuzumab

Substances

  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Trastuzumab