Statins may reduce breast cancer mortality rates

In a recent study published in JAMA Network Open, researchers determined the connection between serological levels of cholesterol, statin usage, and breast cancer (BC) mortality.

Study: Statin Use, Cholesterol Level, and Mortality Amongst Females With Breast Cancer. Image Credit: artemevdokimov/Shutterstock.com

Background

Breast cancer is probably the most prevalent cancer in women internationally, with satisfactory survival rates but poor post-metastasis survival. Statin usage may enhance survival rates in breast cancer patients, in line with research; nevertheless, most trials don’t take underlying blood levels of cholesterol under consideration.

The first cholesterol metabolite, oxysterol 27-hydroxycholesterol, stimulates tumor development and metastasis in BC animal models and has been linked to mortality in females with low estrogen levels.

Cholesterol can also be a precursor for estrogen production, which raises the risk of breast cancer. Previous studies, nevertheless, didn’t consider concurrent levels of cholesterol or changes attributable to statin usage, leading to inconsistent study outcomes.

Concerning the study

In the current population-based, retrospective cohort study, researchers investigated the impact of statin usage and serum levels of cholesterol on breast cancer mortality.

The study included Finnish women with invasive breast cancer that was recently diagnosed between 1 January 1995 and 31 December 2013. All participants provided data on hormone receptors and a number of cholesterol measurements.

BC cases were identified by the Cancer Registry of Finland using the International Classification of Diseases, tenth revision (ICD-10) codes. Data extraction included patient age, diagnosis date, tumor extent and histological features, and first breast cancer treatment.

Before breast cancer diagnosis, mammography screening records were retrieved from the Mass Inspection Registry. The Charlson Comorbidity Index (CCI) values were calculated based on comorbidity data within the Care Register for Health Care database and drug purchase data from the Social Insurance Institution database.

The study exposure was statin use, statin dosage, and serological levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and high-density lipoprotein (LDL), measured pre- and post-breast cancer diagnosis. The final result measure was mortality from breast cancer and other causes between the breast cancer diagnosis date and 31 December 2015.

Cox proportional hazards regression modeling was performed to find out the hazard ratios (HRs). The team excluded females who had higher mortality from breast cancer and other reasons, more metastatic disease or unknown extent of the tumor, and a touch lower percentage with curative-intent surgery as primary therapy. The info were analyzed between January and May 2022.

Results

The study included 13,378 BC patients, amongst whom the median age was 62 years, they usually were followed for a median of 5 years post-breast cancer diagnosis.

Within the follow-up period, 16% of people died, of which seven percent died of breast cancer. In total, 31% of people had elevated total serum levels of cholesterol (median value above 193 mg/dL) before breast cancer diagnosis, and half of the patients had increased total serum cholesterol post-BC diagnosis.

Amongst BC patients, 41% had used statins. The multivariate evaluation showed that statin usage before breast cancer diagnosis was related to an elevated BC mortality risk in comparison with non-use (HR, 1.4).

Pre-diagnostic statin usage increased breast cancer mortality risk even after adjusting for total serum levels of cholesterol (HR, 1.2). Contrastingly, the team observed a reduced breast cancer mortality risk related to post-diagnostic statin usage (HR, 0.9).

The chance decline was higher by increasing statin use intensity (e.g., for low-density lipoprotein, hazard ratios reduced to 0.66 from 0.73). It was robust for people whose serum levels of cholesterol were reduced after statin usage  (HR, 0.5) but was not statistically significant in cases where levels of cholesterol didn’t decline (HR, 0.7). Among the many participants, 980 used statins after breast cancer diagnosis, and the median serum levels of cholesterol were reduced amongst 781 individuals.

Mortality from breast cancer in statin consumers was reduced amongst patients with cancers of the estrogen receptor (ER)-positive type (HR, 0.8) and individuals with localized tumors (HR, 0.6).

Amongst patients with metastatic tumors, statin usage was related to increased mortality in comparison with non-usage (HR, 1.4). Nonetheless, the all-cause mortality rates were lower amongst those that used statins in comparison with non-users adjusting for serological levels of cholesterol (HR, 0.8).

Cholesterol-lowering could also be advantageous since dietary cholesterol and hypercholesterolemia are related to an increased risk of breast cancer. Cell multiplication, membrane construction, and fluidity require cholesterol. Further, cholesterol increases BC cell proliferation and tumor development through ER activation.

Cholesterol can also be a precursor to estrogen production, which is a known carcinogen of the mammary gland. Oxysterol derivatives, comparable to 27-hydroxycholesterol, operate as endogenous ER modulators and may exacerbate cancers amongst women with estrogen deficiency.

Conclusion

Overall, the study findings showed that post-diagnostic statin usage was related to decreased breast cancer mortality than non-usage, mediated by serological levels of cholesterol, indicating that lowering cholesterol with statins may gain advantage breast cancer patients.

BC risk was further reduced with more intensive statin usage, indicating that statin usage might impact BC outcomes through mechanisms apart from reductions in levels of cholesterol.

Nonetheless, amongst females with metastatic tumors, the danger was increased for statin users, indicating that statins might profit only patients with early-stage breast cancers.