Statins may lower cardiotoxic effect of anthracyclines in early breast cancer treatment
Older women who received early breast cancer treatment with anthracycline experienced fewer HF hospitalizations associated with the cardiotoxic effects of chemotherapy when also exposed to statin therapy, researchers reported.
According to data published in the Journal of American Heart Association, a similar trend was observed among women treated with trastuzumab (Herceptin, Genentech), but the association did not meet statistical significance.
“In this population-based, propensity score-matched cohort study, statin-exposed early breast cancer patients at high cardiovascular risk based on older age ( 65 years) had a significantly lower risk of HF hospital presentations following anthracycline-containing chemotherapy compared with matched women who were unexposed to statins,” Husam Abdel-Qadir, MD, PhD, scientist at Women’s College Research Institute, cardiologist at Women’s College Hospital and assistant professor in the department of medicine at the University of Toronto, and colleagues wrote. “There was a nonsignificant trend towards a lower risk of HF hospital presentations associated with statin exposure among trastuzumab-treated women compared with statin-unexposed women.”
Using linked administrative databases for this retrospective cohort study, researchers included 2,545 anthracycline-treated women (859 statin-exposed at baseline) and 1,371 trastuzumab-treated women (520 statin-exposed at baseline), without prior HF, matched 1:1 for the presence of statin exposure at baseline. Women treated with trastuzumab were also matched on anthracycline exposure. Overall, researchers matched 666 statin-discordant pairs of anthracycline-treated women (median age, 69 years) and 390 pairs of trastuzumab-treated women (median age, 71 years).
“Mounting evidence suggests that anthracycline-induced cardiotoxicity is mediated by topoisomerase-2 beta inhibition and oxidative stress secondary to reactive oxygen species generation by anthracyclines,” the researchers wrote. “Oxidative stress may also play a role in trastuzumab-induced cardiotoxicity.”
Researchers observed that the cumulative incidence of HF hospitalization among women treated with anthracyclines was lower among those who also received statin therapy compared with those who did not (P = .01).
Early breast cancer and anthracyclines
At 5 years, the incidence of HF hospitalization among women who received early breast cancer treatment with anthracycline and were statin-exposed was 1.2% (95% CI, 0.5-2.6) compared with 2.9% who were not statin-exposed (95% CI, 1.7-4.6; cause-specific HR = 0.45; 95% CI, 0.24-0.85; P = .01).
In a sensitivity analysis that censored women at time of interim acute MI hospitalization, the 5-year incidence of HF hospitalization in the anthracycline cohort was 1.2% among statin-exposed women (95% CI, 0.5-2.6) and 2.7% among unexposed patients (95% CI, 1.6-4.4; P = .02).
According to the study, the cause-specific HR associated with statin exposure within the anthracycline group was 0.44 (95% CI, 0.22-0.87; P = .02).
In women treated with trastuzumab, the cause-specific HR for HF associated with statin treatment was 0.51 in those without prior anthracyclines use (95% CI, 0.19-1.41; P = .19) and 0.39 in those with prior anthracyclines use (95% CI, 0.1-1.58; P = .19).
Early breast cancer and trastuzumab
Among women with early breast cancer treated with trastuzumab, researchers found a nonsignificant trend toward a lower risk for HF hospitalization among statin-exposed women compared with unexposed women at baseline.
At 5 years, the cumulative incidence of HF hospitalization among women in the trastuzumab group exposed to statin therapy at baseline was 2.7% (95% CI, 1.2-5.2) and 3.7% in the unexposed group (95% CI, 2-6.2; P = .09).
Moreover, among women treated with trastuzumab, the cause-specific HR for HF at 5 years was 0.46 among those exposed to statins (95% CI, 0.2-1.07; P = .07) compared with those with no prior statin use.
After censoring for interim acute MI, the 5-year incidence of HF hospitalization in the trastuzumab group was 2.7% among women exposed to statin therapy (95% CI, 1.2-5.2) and 3.7% among those who were unexposed (95% CI, 2-6.2; cause-specific HR = 0.41; 95% CI, 0.17-0.97: P = .04).
“The results of this study should be interpreted with caution given its retrospective design and dependence on administrative data,” the researchers wrote. “A key limitation is our inability to account for left ventricular ejection fraction, diastolic function, cardiac biomarkers or biohumoral data. Thus, we cannot determine if the HF events occurred with reduced or preserved LVEF. The study excluded women with established diagnoses of HF before chemotherapy but may have included women with asymptomatic cardiomyopathy, although this is not expected to occur more commonly in the nonstatin groups.”