# Statin Use After Breast Cancer Diagnosis Linked to Better Survival in Hormone Receptor-Positive Early Breast Cancer In a large Finnish study of 7,389 women with early breast cancer, women who used cholesterol-lowering statin drugs after their cancer diagnosis had lower death rates from breast cancer. Women who used cholesterol-lowering statin drugs after their cancer diagnosis also had lower death rates from any cause than women who did not use statins. The benefit was strongest in hormone receptor-positive subtypes (luminal A-like, luminal B-like HER2-negative, and luminal B-like HER2-positive). Statin use before diagnosis showed no clear overall survival benefit. The authors conclude that statin therapy may improve survival for patients with early hormone receptor-positive breast cancer. # Statin Use After Breast Cancer Diagnosis Linked to Better Survival in Hormone Receptor-Positive Early Breast Cancer ## Table of Contents - Key Points - Background: Why This Research Matters - How the Study Was Conducted - Who Was in the Study - Statin Use Before Breast Cancer Diagnosis and Survival - Statin Use After Breast Cancer Diagnosis and Survival - Breast Cancer-Specific Mortality Results - All-Cause Mortality Results - Statin Dose and Risk Reduction - Lag-Time Analyses - Sensitivity Analyses - What These Findings Mean for Patients - Limitations of the Study - Recommendations - Frequently Asked Questions - Source Information ## Key Points - In a Finnish study of 7,389 women with early breast cancer, statin use after diagnosis was linked to lower breast cancer and all-cause death rates. - The association was strongest in hormone receptor-positive subtypes: luminal A-like, luminal B-like HER2-negative, and luminal B-like HER2-positive. - Statin use before diagnosis showed no clear overall survival benefit, suggesting timing of statin use may matter. - Higher statin doses were linked to greater reductions in breast cancer-specific mortality, but this needs confirmation in randomized trials. - Patients not on statins should not start them solely based on this study; decisions should be made with a healthcare provider. ## Background: Why This Research Matters Breast cancer was the most frequently diagnosed cancer and the leading cause of cancer-related deaths in women worldwide in 2022. Nearly 2,300,000 new cases and 660,000 deaths occurred globally that year. In Finland, breast cancer was the most common new cancer and the second leading cause of cancer-related death in women in 2022. Breast cancer is a highly heterogeneous disease, meaning that tumors differ significantly from one patient to another. The European Society for Medical Oncology (ESMO) clinical practice guidelines recommend that tumors be managed according to their intrinsic subtypes. These subtypes provide both prognostic information (likely outcome) and predictive information (likely response to treatment). In clinical practice, subtyping is still mostly performed using surrogate definitions. These definitions are based on immunohistochemical or in situ hybridization methods. These methods evaluate hormone receptors (estrogen and progesterone receptors, known as ER and PR), HER2 status, and the proliferation factor Ki-67. Tumors are categorized into five different intrinsic subtypes: - **Luminal A-like** - **Luminal B-like (HER2-negative)** - **Luminal B-like (HER2-positive)** - **HER2-positive (nonluminal)** - **Triple-negative** Statins (3-Hydroxy-3-methylglutaryl coenzyme A, or HMG-CoA, reductase inhibitors) are commonly prescribed drugs. They are used in primary and secondary prevention of cardiovascular diseases. Statins lower cholesterol by inhibiting HMG-CoA. This reduces cholesterol biosynthesis in the liver and increases low-density lipoprotein (LDL) receptors, mostly in hepatocytes (liver cells). The result is a reduction of plasma LDL levels. By inhibiting HMG-CoA, statins also inhibit the metabolism of the mevalonate pathway. This pathway produces isoprenoid proteins. These proteins are vital for regulating cell growth in normal tissues. They are also factors in the RAS oncogene pathway, which is involved in cancer development. Cholesterol is a precursor for steroid hormone synthesis. Cholesterol metabolites have also been associated with stimulation of ER-positive tumor cells in breast cancer. Over two decades of research has shown that statins could be used as anticancer agents. This is due to their antiproliferative, proapoptotic, anti-invasive, and radiosensitizing features. In plain language, these features mean statins may slow cancer cell growth, promote cancer cell death, reduce cancer spread, and make radiation therapy more effective. Despite some contradictory works, several previous studies and meta-analyses have suggested that statin use is associated with improved survival in patients with breast cancer. Most earlier studies focused on statin use after breast cancer diagnosis. There is also evidence on the association of prediagnostic statin use and improved breast cancer survival. Notably, previous studies have been widely heterogeneous. Most studies included patients with advanced-stage breast cancer and some with in situ tumors (non-invasive tumors). Furthermore, a few previous studies suggested a more pronounced benefit of statin use among patients with hormone receptor-positive breast cancer. However, no studies have examined the outcomes of statins in different intrinsic breast cancer subtypes. Besides earlier efforts by this research group, other studies have not been able to assess the association between time-dependent statin dose and mortality of patients with breast cancer. Other studies have not been able to assess the outcomes of statin dose in different intrinsic subtypes. The aim of this study was to assess the associations between prediagnostic and postdiagnostic statin use and all-cause and breast cancer-specific survival. The aim was to assess these associations according to different intrinsic breast cancer subtypes in patients with early breast cancer. To further understand the role of statin use, the researchers also performed dose-dependency analyses. ## How the Study Was Conducted This was a retrospective population-based cohort study. The researchers used a subpopulation of a retrospective population-based cohort including all female patients diagnosed with invasive breast cancer in Finland between January 1, 1995, and December 31, 2013. Each patient's follow-up period started from breast cancer diagnosis and continued until death, emigration, or the end of follow-up on December 31, 2015. Patients with breast cancer were identified from The Finnish Cancer Registry. This is a nationwide registry covering 99% of cancer cases nationally. The researchers used International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes between C50.1 and C50.9. The study permission was granted by the Institute for Health and Welfare (THL). Permissions for data use were granted by the aforementioned registries. According to national law and regulations, the study did not require informed consent from the patients nor ethics committee review due to its retrospective nature. The researchers adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies. Before anonymizing the data, individual social security numbers of patients diagnosed with breast cancer were used to link and gather information from different registries. The data collected included: - Age at diagnosis, disease extent, initial treatment selection, and mammography screening participation from The Finnish Cancer Registry and The Finnish Mass Screening Registry - Tumor characteristics and histopathological information as well as blood cholesterol measurements from 2 large public laboratories (Tykslab at Turku University Hospital and Fimlab at Tampere University Hospital) - Information regarding deaths and causes of death from the national death certificate registry maintained by Statistics Finland - Information on comorbidities (ICD-10 diagnosis codes) and medical procedures from the nationwide Care Register for Health Care maintained by THL ICD-10 diagnosis codes were used to calculate the Charlson Comorbidity Index (CCI), a measure of overall health burden from other diseases. Patients in the cohort were all primarily treated with curative intent. Therefore, breast cancer-specific mortality was driven by distant breast cancer recurrence. The researchers included only patients with early breast cancer (localized or locally advanced tumors) and sufficient information (ER, PR, Ki-67, and HER2 status) for classification into different subtypes. Patients' tumors were classified into 5 different intrinsic subtypes. The classification used clinicopathological surrogate definitions adapted from the 2013 St Gallen Consensus Conference and the ESMO guidelines. The subtypes were luminal A-like, luminal B-like (HER2-negative), luminal B-like (HER2-positive), HER2-positive (nonluminal), and triple-negative. **How statin use was measured:** Statins are not sold over the counter in Finland. They are prescribed by physicians and partly reimbursed by the Social Insurance Institution (SII). The researchers collected data on individual patients' statin purchases between 1995 and 2015 from the SII drug prescription database. This database covers all reimbursed drug purchases. The drug purchase data included information on the package size and drug strength of every purchase. For each year, the researchers added together all the statin purchases to calculate an annual total use of each statin in milligrams for each patient. Statin use was then standardized by dividing the annual purchased total milligram amount of each statin by their drug-specific defined daily dose (DDD) as posed by the World Health Organization. Patients were considered prediagnostic statin users if they had any purchases of statins between 1995 and the year of their breast cancer diagnosis. All patients were considered nonusers until the year of their first statin purchase. Every year with a purchase of statins, irrespective of the amount, was recorded as a year with statin use. After the first statin purchase, patients were not allowed to transfer back to being nonusers. This was done to limit bias regarding discontinuation of statin use in the palliative care phase. An intensity variable to estimate annual statin dose was generated by calculating cumulative DDD and dividing it with the cumulative duration of statin use. **Statistical methods:** The researchers performed statistical analyses with IBM SPSS for Windows, version 28.0. Statistical analyses were performed from September to November 2023. A Cox proportional hazards regression model was used to evaluate the risk of all-cause and breast cancer-specific mortality (hazard ratio [HR] and 95% CI) between prediagnostic and postdiagnostic statin use. The model was used to evaluate the risk between different subsets of intrinsic breast cancer subtypes. Statistical significance was assessed using 95% CI boundaries without multiple testing correction. Results were considered statistically significant when both the lower and upper 95% CI was either below or above 1.00. The researchers performed Cox regression analyses with age and multivariable adjustment. The adjusting factors were age at breast cancer diagnosis and number of mammography screening rounds attended before breast cancer diagnosis. The adjusting factors were diabetes (all types) before breast cancer diagnosis and primary treatment for breast cancer (surgery or other or unknown). The adjusting factors were anticoagulative and antihypertensive drug use after breast cancer diagnosis, and CCI. In the first sensitivity analysis, the researchers adjusted the multivariable-adjusted model also for blood cholesterol level after breast cancer diagnosis. In the second sensitivity analysis, they performed the standard multivariable-adjusted Cox regression model without CCI. To minimize immortal time bias (a type of error where a period of time is misclassified), postdiagnostic statin use and blood cholesterol levels were analyzed as time-dependent variables. The status of statin use and blood cholesterol level were updated every year starting from the year of breast cancer diagnosis. The researchers also conducted 1-year and 3-year lag-time analyses to acknowledge the possibility of protopathic bias (where early symptoms of cancer affect the exposure). The researchers also conducted these analyses to analyze possible delayed associations of statin use. ## Who Was in the Study The study population consisted of 7,389 female patients with early breast cancer. The median age at diagnosis was 60 years, with a range from 21 to 102 years. The median follow-up time after breast cancer diagnosis was 6.5 years, with a range from 0.0 to 19.6 years. Of the patients, 1,254 (17.0%) had used statins before breast cancer diagnosis, and 2,313 (31.3%) had used statins after breast cancer diagnosis. Statin users were older compared with nonusers. The median age for statin users was 64 years (range 34-93) versus 58 years (range 21-102) for nonusers. Altogether, 1,673 deaths occurred during follow-up. Of these, 704 (42.1%) were breast cancer-related. Luminal B-like (HER2-negative) was the most frequent subtype with 3,669 cases (49.7%). The distribution of subtypes was as follows: - **Luminal A-like:** 2,124 patients (28.7%) - **Luminal B-like (HER2-negative):** 3,669 patients (49.7%) - **Luminal B-like (HER2-positive):** 563 patients (7.6%) - **HER2-positive (nonluminal):** 374 patients (5.1%) - **Triple-negative:** 659 patients (8.9%) Among patients who used statins after diagnosis, 1,059 (45.8%) had also used statins before diagnosis. Among patients who did not use statins after diagnosis, only 195 (3.8%) had used statins before diagnosis. Regarding tumor characteristics, 5,729 patients (77.5%) had ductal histology, 1,268 (17.2%) had lobular histology, and 390 (5.3%) had other histology. Tumor extent at diagnosis was localized in 4,583 patients (62%) and locally advanced in 2,806 patients (38.0%). Primary treatment was surgery with curative intent in 6,020 patients (81.5%). Other or unknown primary treatment was recorded in 1,369 patients (18.5%). Comorbidities were similar between groups. The median Charlson Comorbidity Index was 0 (range 0-2) in both statin users and nonusers. Diabetes before breast cancer diagnosis was present in 535 patients (7.2%) overall, but was more common in statin users (330 patients, 14.3%) than nonusers (205 patients, 4.0%). Hypertension before breast cancer diagnosis was present in 3,329 patients (45.1%) overall, and was also more common in statin users (1,443 patients, 62.4%) than nonusers (1,886 patients, 37.2%). ## Statin Use Before Breast Cancer Diagnosis and Survival Prediagnostic statin use was not associated with breast cancer-specific mortality in the whole study population. In the whole population, breast cancer-specific mortality occurred in 89 of 1,254 statin users (7.1%) compared with 615 of 6,135 nonusers (10.0%). The age-adjusted hazard ratio was 0.85 (95% CI, 0.68-1.07), and the multivariable-adjusted hazard ratio was 0.86 (95% CI, 0.68-1.09). Because the confidence interval crosses 1.00, this result was not statistically significant. Furthermore, statin use before breast cancer diagnosis was not associated with breast cancer-related mortality in any subtype, apart from the luminal B-like (HER2-positive) subtype. In that subtype, mortality was lower in statin users compared with nonusers. The multivariable-adjusted hazard ratio was 0.33 (95% CI, 0.12-0.87), which was statistically significant. Prediagnostic statin use was not associated with all-cause mortality in the whole study population or in any different intrinsic subtype. In the whole population, all-cause mortality occurred in 288 of 1,254 statin users (23.0%) compared with 1,385 of 6,135 nonusers (22.6%). The age-adjusted hazard ratio was 0.97 (95% CI, 0.85-1.11), and the multivariable-adjusted hazard ratio was 0.94 (95% CI, 0.83-1.08). Subtype-specific results for prediagnostic statin use and all-cause mortality were as follows: - **Luminal A-like:** 65 deaths in 342 statin users (19.0%) vs 340 deaths in 1,782 nonusers (19.1%); multivariable-adjusted HR, 0.98 (95% CI, 0.74-1.28) - **Luminal B-like (HER2-negative):** 147 deaths in 659 statin users (22.3%) vs 712 deaths in 3,010 nonusers (23.7%); multivariable-adjusted HR, 0.92 (95% CI, 0.76-1.10) - **Luminal B-like (HER2-positive):** 26 deaths in 91 statin users (28.6%) vs 108 deaths in 472 nonusers (22.9%); multivariable-adjusted HR, 0.74 (95% CI, 0.45-1.22) - **HER2-positive (nonluminal):** 14 deaths in 60 statin users (23.3%) vs 72 deaths in 314 nonusers (22.9%); multivariable-adjusted HR, 0.81 (95% CI, 0.43-1.52) - **Triple-negative:** 36 deaths in 102 statin users (35.3%) vs 153 deaths in 557 nonusers (27.5%); multivariable-adjusted HR, 0.98 (95% CI, 0.66-1.46) ## Statin Use After Breast Cancer Diagnosis and Survival The distribution of intrinsic subtypes between postdiagnostic statin users and nonusers was relatively similar. The disease extent at diagnosis did not differ between statin users and nonusers. Postdiagnostic statin use was associated with lower age-adjusted and multivariable-adjusted breast cancer-specific mortality and all-cause mortality in the whole cohort. The details of these findings are described in the sections below. ## Breast Cancer-Specific Mortality Results Postdiagnostic statin use was associated with lower age-adjusted breast cancer-specific mortality in the whole cohort. The age-adjusted hazard ratio was 0.68 (95% CI, 0.57-0.82). In the multivariable-adjusted model, the hazard ratio was 0.59 (95% CI, 0.48-0.71). Both results were statistically significant. In the whole cohort, breast cancer-specific mortality occurred in 128 of 2,313 statin users (5.5%) compared with 576 of 5,076 nonusers (11.3%). The risk for breast cancer-specific mortality among statin users was reduced in all of the hormone receptor-positive subtypes (luminal A-like, luminal B-like [HER2-negative], and luminal B-like [HER2-positive]). This reduction was seen in both age-adjusted and multivariable-adjusted analyses. Subtype-specific results for breast cancer-specific mortality were as follows: - **Luminal A-like:** 21 breast cancer deaths in 702 statin users (3.0%) vs 103 in 1,422 nonusers (7.2%); age-adjusted HR, 0.62 (95% CI, 0.40-0.96); multivariable-adjusted HR, 0.52 (95% CI, 0.33-0.83) - **Luminal B-like (HER2-negative):** 70 breast cancer deaths in 1,170 statin users (6.0%) vs 297 in 2,499 nonusers (11.9%); age-adjusted HR, 0.66 (95% CI, 0.51-0.85); multivariable-adjusted HR, 0.62 (95% CI, 0.47-0.80) - **Luminal B-like (HER2-positive):** 7 breast cancer deaths in 141 statin users (5.0%) vs 64 in 422 nonusers (15.2%); age-adjusted HR, 0.43 (95% CI, 0.21-0.88); multivariable-adjusted HR, 0.29 (95% CI, 0.14-0.62) - **HER2-positive (nonluminal):** 9 breast cancer deaths in 109 statin users (8.3%) vs 30 in 265 nonusers (11.3%); age-adjusted HR, 1.05 (95% CI, 0.48-2.29); multivariable-adjusted HR, 0.69 (95% CI, 0.30-1.60) - **Triple-negative:** 21 breast cancer deaths in 191 statin users (11.0%) vs 82 in 468 nonusers (17.5%); age-adjusted HR, 0.98 (95% CI, 0.61-1.57); multivariable-adjusted HR, 0.72 (95% CI, 0.43-1.20) ## All-Cause Mortality Results Postdiagnostic statin use was associated with lower age-adjusted all-cause mortality in the whole cohort. The age-adjusted hazard ratio was 0.83 (95% CI, 0.75-0.92). In the multivariable-adjusted model, the hazard ratio was 0.68 (95% CI, 0.61-0.76). Both results were statistically significant. In the whole cohort, all-cause mortality occurred in 407 of 2,313 statin users (17.6%) compared with 1,266 of 5,076 nonusers (24.9%). Age-adjusted and multivariable-adjusted all-cause mortality was lower among statin users in luminal A-like and luminal B-like (HER2-negative) subtypes. Only the multivariable-adjusted risk reduction reached statistical significance in luminal B-like (HER2-positive) and triple-negative subtypes. Subtype-specific results for all-cause mortality were as follows: - **Luminal A-like:** 96 deaths in 702 statin users (13.7%) vs 309 in 1,422 nonusers (21.7%); age-adjusted HR, 0.72 (95% CI, 0.58-0.89); multivariable-adjusted HR, 0.59 (95% CI, 0.47-0.74) - **Luminal B-like (HER2-negative):** 215 deaths in 1,170 statin users (18.4%) vs 644 in 2,499 nonusers (25.8%); age-adjusted HR, 0.84 (95% CI, 0.73-0.98); multivariable-adjusted HR, 0.72 (95% CI, 0.61-0.83) - **Luminal B-like (HER2-positive):** 25 deaths in 141 statin users (17.7%) vs 109 in 422 nonusers (25.8%); age-adjusted HR, 0.81 (95% CI, 0.54-1.20); multivariable-adjusted HR, 0.51 (95% CI, 0.32-0.79) - **HER2-positive (nonluminal):** 24 deaths in 109 statin users (22.0%) vs 62 in 265 nonusers (23.4%); age-adjusted HR, 1.08 (95% CI, 0.68-1.72); multivariable-adjusted HR, 0.89 (95% CI, 0.54-1.45) - **Triple-negative:** 47 deaths in 191 statin users (24.6%) vs 142 in 468 nonusers (30.3%); age-adjusted HR, 0.96 (95% CI, 0.69-1.33); multivariable-adjusted HR, 0.70 (95% CI, 0.49-0.99) ## Statin Dose and Risk Reduction When analyzing the outcomes of the statin dose, the researchers observed a dose-dependent risk reduction in breast cancer-specific mortality in the whole cohort. This means that higher statin doses were associated with greater reductions in breast cancer death risk. In the whole cohort, the breast cancer-specific mortality results by statin dose tertile (thirds of the dose range) were: - **First tertile (lowest dose):** 61 breast cancer deaths in 813 patients (7.5%); age-adjusted HR, 0.81 (95% CI, 0.61-1.06); multivariable-adjusted HR, 0.73 (95% CI, 0.55-0.96) - **Second tertile (middle dose):** 39 breast cancer deaths in 746 patients (5.2%); age-adjusted HR, 0.61 (95% CI, 0.44-0.85); multivariable-adjusted HR, 0.52 (95% CI, 0.38-0.73) - **Third tertile (highest dose):** 28 breast cancer deaths in 754 patients (3.7%); age-adjusted HR, 0.52 (95% CI, 0.36-0.77); multivariable-adjusted HR, 0.45 (95% CI, 0.30-0.66) Similar trends of dose-dependency were also seen in breast cancer-specific mortality in the largest subtypes, luminal A-like and luminal B-like (HER2-negative). Similar trends of dose-dependency were also seen partly in the luminal B-like (HER2-positive) subtype. However, the sample size was not large enough to reach statistical significance in most tertiles. In the whole population, the risk reduction among statin users regarding all-cause mortality was somewhat similar irrespective of the statin dose. Statin use did not seem to have a dose-dependent risk reduction in all-cause mortality, apart from a possible trend seen in the luminal B-like (HER2-positive) subtype in multivariable-adjusted analysis. For all-cause mortality in the whole cohort by statin dose: - **First tertile:** 165 deaths in 813 patients (20.3%); age-adjusted HR, 0.81 (95% CI, 0.68-0.96); multivariable-adjusted HR, 0.69 (95% CI, 0.58-0.82) - **Second tertile:** 133 deaths in 746 patients (17.8%); age-adjusted HR, 0.75 (95% CI, 0.63-0.90); multivariable-adjusted HR, 0.62 (95% CI, 0.52-0.75) - **Third tertile:** 109 deaths in 754 patients (14.5%); age-adjusted HR, 0.81 (95% CI, 0.67-0.98); multivariable-adjusted HR, 0.65 (95% CI, 0.53-0.79) ## Lag-Time Analyses In 1-year lag-time analysis, the risk reduction of mortality in statin users was relatively similar in the whole cohort compared with analyses without lag-time. This was true when considering both breast cancer-specific mortality and all-cause mortality. For breast cancer-specific mortality in the 1-year lag-time analysis: - Age-adjusted HR, 0.72 (95% CI, 0.60-0.88) - Multivariable-adjusted HR, 0.63 (95% CI, 0.52-0.77) For all-cause mortality in the 1-year lag-time analysis: - Age-adjusted HR, 0.85 (95% CI, 0.77-0.95) - Multivariable-adjusted HR, 0.71 (95% CI, 0.63-0.79) The 3-year lag-time results for all-cause mortality in the combined population were statistically significant only in multivariable-adjusted analysis. For breast cancer-specific mortality, the risk reductions were still statistically significant, but the risk reduction decreased as the lag-time increased. The lag-time results were analyzed in different subtypes. In this analysis, the 1-year lag-time age-adjusted risk reduction for breast cancer-related mortality was observed in luminal B-like (HER2-negative) and luminal B-like (HER2-positive) subtypes. The 1-year lag-time multivariable-adjusted risk reductions were statistically significant in luminal A-like, luminal B-like (HER2-negative), and luminal B-like (HER2-positive) subtypes. The magnitude of risk reduction weakened with the prolongation of the lag-time. With 3 years' time lag, breast cancer-specific mortality remained statistically significantly decreased only for the luminal B-like (HER2-positive) subtype. ## Sensitivity Analyses There was a total of 3,244 patients with at least 1 measurement of blood cholesterol level after breast cancer diagnosis eligible for the first sensitivity analysis. In the first sensitivity analysis, the model for all-cause and breast cancer-specific mortality was also adjusted for blood cholesterol levels after breast cancer diagnosis. In this sensitivity analysis, statin use was associated with higher survival in the whole population: - Breast cancer-specific mortality HR, 0.67 (95% CI, 0.49-0.90) - All-cause mortality HR, 0.66 (95% CI, 0.56-0.78) Statin use also lowered breast cancer-specific mortality in the luminal B-like (HER2-negative) subtype. All-cause mortality was lowered in luminal A-like and luminal B-like (HER2-negative) subtypes. The researchers performed a second sensitivity analysis in the whole population for postdiagnostic statin use where CCI was not used in the multivariable-adjusted analyses. The exclusion of CCI did not affect the results. In a third sensitivity analysis, the researchers conducted a new-user analysis where they excluded all patients with prediagnostic statin use. The exclusion of prediagnostic statin users did not affect the results. ## What These Findings Mean for Patients This study found that postdiagnostic statin use was associated with lower all-cause and breast cancer-specific mortality among patients with hormone receptor-positive intrinsic subtypes. These findings suggest that statin therapy may improve survival of patients with early hormone receptor-positive subtypes. The benefit of statin use was noticed in all statin users regardless of dose intensity. However, a trend of dose-dependent risk reduction was observed regarding breast cancer-specific mortality. This means that patients who took higher doses of statins had a greater reduction in breast cancer death risk. The results were consistent across several analyses. One-year lag-time analysis or adjustment for blood cholesterol levels after breast cancer diagnosis did not affect the results substantially. This consistency strengthens the reliability of the findings. Importantly, prediagnostic statin use was not associated with higher survival. This suggests that the timing of statin use matters. Starting statins after breast cancer diagnosis may be more beneficial than using them before diagnosis. The study also found that the association between statin use and improved survival was strongest in hormone receptor-positive subtypes. These subtypes include luminal A-like, luminal B-like (HER2-negative), and luminal B-like (HER2-positive). For patients with these subtypes, statin use was associated with better breast cancer-specific survival. For patients with HER2-positive (nonluminal) and triple-negative subtypes, the results were less clear. All-cause mortality was lower among statin users in patients with hormone positive and triple-negative subtypes. However, the breast cancer-specific mortality results did not reach statistical significance in these subtypes. ## Limitations of the Study This was a retrospective cohort study, which means it looked back at existing data rather than following patients forward in time. This type of study can show associations but cannot prove that statins directly cause improved survival. The researchers used surrogate definitions for intrinsic subtyping based on immunohistochemical or in situ hybridization methods. These methods evaluate hormone receptors, HER2, and Ki-67 status. While these are standard in clinical practice, they are not the same as molecular or genetic technologies for subtyping. The study included only patients with early breast cancer (localized or locally advanced tumors). The findings may not apply to patients with advanced or metastatic breast cancer. Statin users were older compared with nonusers. The median age for statin users was 64 years versus 58 years for nonusers. Statin users also had more comorbidities, including diabetes and hypertension. The researchers adjusted for these factors in their analyses, but residual confounding is possible. The sample size was not large enough to reach statistical significance in most tertiles for some subtypes, particularly the smaller subtypes like HER2-positive (nonluminal) and triple-negative. The study did not require informed consent from patients nor ethics committee review due to its retrospective nature. This is allowed under national law and regulations for this type of study. The researchers did not perform multiple testing correction. Statistical significance was assessed using 95% CI boundaries. Results were considered statistically significant when both the lower and upper 95% CI was either below or above 1.00. ## Recommendations Based on these findings, the researchers suggest that statin therapy may improve survival of patients with early hormone receptor-positive subtypes. However, this was an observational study, and the results need to be confirmed in randomized clinical trials before statins can be routinely recommended as part of breast cancer treatment. Patients with early breast cancer who are already taking statins for cardiovascular reasons should discuss their statin use with their oncology team. The study found that postdiagnostic statin use was associated with better survival, particularly in hormone receptor-positive subtypes. Patients who are not taking statins should not start taking them solely based on this study. Statins are prescription medications that carry their own risks and benefits. Any decision to start statin therapy should be made in consultation with a healthcare provider. The dose-dependency findings suggest that higher statin doses may be associated with greater reductions in breast cancer-specific mortality. However, this finding needs confirmation in clinical trials. Patients should not increase their statin dose without medical supervision. Future research should include randomized clinical trials to confirm whether statins directly improve breast cancer survival. Such trials should examine different intrinsic subtypes and different statin doses. Patients should continue to follow their recommended breast cancer treatment plans. Statin use should be considered as a potential additional therapy, not a replacement for standard treatments such as surgery, chemotherapy, radiation therapy, or hormone therapy. ## Frequently Asked Questions ### What did this research find about statins and breast cancer survival? In a Finnish study of 7,389 women with early breast cancer, those who used cholesterol-lowering statins after diagnosis had lower death rates from breast cancer and from any cause than non-users. The benefit was strongest in hormone receptor-positive subtypes. Statin use before diagnosis showed no clear overall survival benefit. The authors conclude statin therapy may improve survival for early hormone receptor-positive breast cancer. ### Does this mean I should start taking a statin after my breast cancer diagnosis? No. The researchers say patients not already taking statins should not start them solely based on this study. Statins are prescription medicines with their own risks and benefits. Any decision to start statin therapy should be made with a healthcare provider. This was an observational study, and results need confirmation in randomized clinical trials before statins can be routinely recommended as part of breast cancer treatment. ### I already take a statin for cholesterol. What should I do? Patients with early breast cancer who are already taking statins for cardiovascular reasons should discuss their statin use with their oncology team. The study found that statin use after diagnosis was associated with better survival, particularly in hormone receptor-positive subtypes. Do not change your dose without medical supervision. Your statin should be considered a potential additional therapy, not a replacement for standard breast cancer treatments. ### Which breast cancer subtypes seemed to benefit most from statin use after diagnosis? The association with lower breast cancer-specific mortality was seen in all hormone receptor-positive subtypes: luminal A-like, luminal B-like HER2-negative, and luminal B-like HER2-positive. For HER2-positive nonluminal and triple-negative subtypes, results were less clear and did not reach statistical significance for breast cancer-specific mortality. All-cause mortality was lower among statin users in hormone-positive and triple-negative subtypes. ### Did the dose of statin matter? In the whole group, higher statin doses were associated with greater reductions in breast cancer death risk. Breast cancer-specific mortality fell from 7.5% in the lowest dose tertile to 3.7% in the highest. For all-cause mortality, risk reduction was similar across doses. However, this dose-dependency finding needs confirmation in clinical trials, and patients should not increase their statin dose without medical supervision. ### What are the limitations of this research? This was a retrospective cohort study, so it can show associations but cannot prove statins directly cause improved survival. It included only patients with early breast cancer, so findings may not apply to advanced or metastatic disease. Statin users were older and had more diabetes and hypertension, and residual confounding is possible. Some smaller subtypes had too few patients to reach statistical significance. ### Should I stop my standard breast cancer treatment to take statins instead? No. Patients should continue to follow their recommended breast cancer treatment plans. Statin use should be considered as a potential additional therapy, not a replacement for standard treatments such as surgery, chemotherapy, radiation therapy, or hormone therapy. Any decision about statin therapy should be made in consultation with a healthcare provider, alongside your ongoing cancer treatment. ### I have early hormone receptor-positive breast cancer — when should I seek a second opinion about statins? A second opinion is worth considering when you have early hormone receptor-positive breast cancer and want clarity on whether statins belong in your care. Postdiagnostic statin use was associated with lower breast cancer-specific and all-cause mortality in luminal A-like, luminal B-like HER2-negative, and luminal B-like HER2-positive subtypes, with a dose-dependent reduction in breast cancer death risk. Prediagnostic use showed no clear survival benefit. These findings are observational and need confirmation in randomized trials, so patients not already on statins should not start them solely on this basis. Diagnostic Detectives Network provides independent expert second opinions. ## Source Information **Original article title:** Statin Use and Survival in Early Breast Cancer According to Different Intrinsic Subtypes **Authors:** Santeri Palmi, MD; Otso Arponen, PhD; Mika Murto, MD; Aino Siltari, PhD; Arja Jukkola, PhD; Teemu Murtola, PhD **Publication:** JAMA Network Open. 2026;9(6):e2616375. doi:10.1001/jamanetworkopen.2026.16375 **Article type:** Original Investigation, Oncology **Open Access:** This is an open access article distributed under the terms of the CC-BY-NC-ND License, which does not permit alteration or commercial use, including those for text and data mining, AI training, and similar technologies. *This patient-friendly article is based on peer-reviewed research.* --- Publisher: Diagnostic Detectives Network (https://diagnosticdetectives.com) — independent multi-expert medical second opinions, worldwide, private-pay. Author byline: Anton Titov, MD, PhD. 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