Can rosuvastatin protect against chemo-induced cardiotoxicity in HER2+ breast cancer?

Use of rosuvastatin is associated with a significantly lower decline in left ventricular ejection fraction (LVEF) and lower serum levels of cardiotoxicity-associated biomarkers in newly diagnosed HER2-positive breast cancer patients treated with anthracycline-based chemotherapy followed by trastuzumab, according to the results of a prospective, randomized, controlled, parallel study.

Doxorubicin is an anthracycline widely used in the treatment of breast cancer, which causes non-reversible, dose-dependent type 1 cardiotoxicity. Clinical trials have shown that subsequent use of trastuzumab is associated with high levels of cardiotoxicity as it affects cell survival and repair, which exacerbates the damage induced by prior doxorubicin therapy. [Eur Rev Med Pharmacol Sci 2018;22:2175-2185]

“Rosuvastatin is believed to have antioxidant and anti-inflammatory effects that may help to prevent DNA damage and provide cardioprotective effect,” wrote the researchers. [Atherosclerosis 2008;199:87] “In this study, we investigate the possible protective effect of rosuvastatin in chemotherapy-induced cardiotoxicity in HER2-positive breast cancer patients.”

Fifty newly diagnosed HER2-positive breast cancer female patients (age, 25–75 years) received doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² on day 1 of every 21-day cycle for four cycles, followed by paclitaxel 80 mg/m² weekly for 12 weeks, with trastuzumab 4 mg/kg given with first dose of paclitaxel followed by trastuzumab 2 mg/kg weekly. Half of the patients (rosuvastatin group, n=25) received 20 mg of oral rosuvastatin 24 hours before the first cycle of chemotherapy and once daily for the rest of the follow-up period (6 months), while the patients in the control group (n=25) did not. [Med Oncol 2024;41:196]

The patients in the two groups had similar LVEF at baseline (rosuvastatin group: 66.68 percent; control group: 68.96 percent). After 3 months of treatment, LVEF declined by 1.36 vs 4.6 percent in rosuvastatin vs control group (p=0.036). After 6 months, LVEF declined by 3.44 percent in rosuvastatin group and 8.2 percent in the control group (p=0.002).

In addition, a significant difference in incidence of cardiotoxicity was detected between the two studied groups (p=0.037). Four patients (16 percent) in the control group vs no patients in rosuvastatin group experienced cardiotoxicity during the study period.

Since changes in serum biomarkers are more sensitive than LVEF decline, the researchers assessed high-sensitivity cardiac troponin I (hs-cTnI), myeloperoxidase (MPO), and interleukin-6 (IL-6) levels to detect subclinical cardiotoxicity. hs-cTnI is an early predictor of myocardial damage; its level was significantly lower among rosuvastatin-treated patients vs control patients after 3 (p=0.026) and 6 months (p=0.046). [Circulation 2004;109:2749-2754] MPO is a marker of oxidative stress and inflammation that is elevated in patients with heart failure and cardiac dysfunction. [J Am Coll Cardiol 2007;49:2364-2370] While no significant difference in MPO level was observed between the two groups after 3 months, patients in rosuvastatin group had significantly lower MPO level vs control patients after 6 months (p=0.014). IL-6 is a biomarker for inflammation linked to higher risk of cardiovascular events. [J Cardiovasc Transl Res 2020;13:431-450] Compared with control group, rosuvastatin-treated patients had significantly lower IL-6 after 3 (p=0.023) and 6 months (p=0.001).

“Our results demonstrate that rosuvastatin can protect against cardiotoxicity associated with breast cancer therapy, especially doxorubicin and trastuzumab, as assessed by LVEF and confirmed by specific cardiac inflammatory markers,” summarized the researchers.

No additional side effects were reported in rosuvastatin vs control group throughout the study. Alanine aminotransferase levels had remained unaltered in both groups, implying rosuvastatin did not have any significant effect on patients’ liver function.