STATINS

There is clear evidence that there are sub groups of patients responding to statins with both lowered cholesterol markers and reduced progression risks. As with all treatments, specific targeting is needed even down to the type and dose of statin. Its also important to realize the risk reductions that do occur are substantial, if this were data on adding further oncology drugs it would be headlined as some major breakthrough.

Studies of statin impacts are mostly from large numbers of patient records, where both pre and post diagnosis use of statins can be assessed vs progression risks. Direct interventional trial results continue to emerge, but more are needed. Multiple trials are ongoing alongside various oncology treatments to refine when and how to apply them. Atorvastatin and simvastatin are the commonly researched statins as additional drugs for breast, prostate, gastrointestinal, liver and other cancers.

Illustrating differing findings in breast cancer patient data, a 2021 reports that the risk reductions seen from statins were specific to early phase triple negative type cancers. Whilst a more recent study showed that the important criteria was not breast cancer type, but that statins resulted in a clear lowering of cholesterol levels. That 2023 Finnish breast cancer study showed specifically ER+, PR- and HER2+ patients , those with localized disease approximately halved their risks for progression. This is focused in about eight percent of case records that featured post diagnostic statin use, and 80% of these responded with lowered cholesterol levels (Highlight 1 & 2). And a similar survey of patients in Norway found 16% reduced risks for statin users, higher for ER- and TNBC types. A New Zealand-based study found post-diagnostic statin use and reduced risk around 26% mainly in ER positive patients, postmenopausal women, and those with advanced-stage disease.

A new 2025 study across multiple trials in leukemia and non hodgkin lymphoma types recently reported over 60% reduced risk from cancer related mortality. This data was for patients treated with the tyrosine kinase inhibtor ibrutinib. In total nearly 1500 cases are included, and the effects are very substantially positive, it remains to be shown if all patients can benefit from statins or if its particular sub groupings.

Patient records from lung cancer outcomes have broadly shown lower risks in those patients taking statins, some of which are in large impacts. Even pancreatic cancer has been gathering studies showing measurable advantages to statins during oncology, including immunotherapy. Similar effects are emerging in head and neck cancers.

A high quality analysis of swedish ulcerative colitis patients statin use vs the incidence and progression of colorectal cancer in was published recently. Results showed post diagnosis risk reductions of approximately a half, and about a third lower all cause mortality (Highlight 3). Analysis on liver cancers found about 15% risk reductions, while in gastric cancer case history some reports find 1/3 to 2/3 lower progresssion risks. In advanced kidney cancer, similar analysis shows around 22% relative risk reductions with statin use. At least one trial shows improved outcomes with TKI (eg carbozantinib, sunitinib) treatment in clear cell kidney cancer. (see References)

In prostate cancer, a recent case controlled analysis showed measurably improved benefits in progression with 32% relative risk reduction. Another analysis across multiple studies from 2022 shows typical relative risk reductions are 27%. Importantly, and in contrast to most drugs, there are small studies showing important reductions to oncology side effects related to sexual function from androgen therapy with lovastatin (see References, and red yeast rice in the Supplements Library)

There are indications from some studies that the presence of low dose aspirin and/ or anti-diabetics have enhanced these effects. And interesting reports that red yeast rice, which is equivalent to lovastatin, can combine with nattokinase to improve crucial markers associated with metastatic spread.

Next, we examined the association of incident statin use with outcomes according to statin type and statin intensity stratified by TNBC versus non-TNBC status… Among individuals with TNBC, we observed a statistically significant association between incident use of Lipophilic-statins and improved Overall Survival (HR, 0.66) [Hazard Ratio], with a directionally consistent effect on BCSS [breast cancer specific survival] (SHR, 0.5). When examining statin intensity, high-intensity statin use had the strongest effect on OS among individuals with...

In this comprehensive cohort study, the inverse association between statin use and BC mortality was partly mediated by underlying cholesterol level. The risk decrease by statin use was clear only when the serum cholesterol level decreased simultaneously, although the subgroup analyses were limited by low statistical power. This finding suggests that serum cholesterol may be an important factor in BC and that the previously reportd inverse association between statin use and BC mortality is likely mediated by underlying cholesterol level changes. N...

During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) [nearly 30% lowered risk of CRC] ..The benefit for incident CRC was duration-dependent…: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 for 1 to <2 years of use, 0.46 for 2 to <5 years of use, and 0.38 for ≥5 years of use. Compared with non-users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9 [nearly 2X lower]an...

This systematic review and meta-analysis studied the association between statin use and survival outcomes in men using androgen-ablative therapies for advanced prostate cancer. In pooling data from 25 cohorts and 119 878 men, we identified an association of statin use with a 27% overall mortality and 35% PCSM benefit.. Subgroup analyses suggested a preferential advantage for men receiving ARATs. These findings were not driven by any single cohort, withstood robust sensitivity analyses, and were free of publication bias.

TABLE OF REFERENCES

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https://www.sciencedirect.com/science/article/pii/S2473952925002435	5	This study provides valuable insights into the associations of baseline statin use with survival and adverse event outcomes in patients with CLL/SLL initiating contemporary treatment regimens. The findings revealed a statistically significant association between statin utilization and improved OS, PFS, and cancer-specific survival. The latter suggests a potential disease-modifying effect of statins in this patient population. No significant associations were observed between statin use and the occurrence of grade ≥3 adverse events.	In conclusion, our findings demonstrate for the first time that the concurrent use of statins in a diverse population of treatment-naïve or relapsed/refractory patients with CLL/SLL initiating contemporary treatment regimens, including ibrutinib, is significantly associated with improved OS and PFS. Further research is warranted to explore the underlying mechanisms by which statins exert their beneficial effects in patients with CLL/SLL and to investigate whether these associations vary between different statin classes and treatment regimens
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33797	4.5	Next, we examined the association of incident statin use with outcomes according to statin type and statin intensity stratified by TNBC versus non-TNBC status (Table 2). Among individuals with TNBC, we observed a statistically significant association between incident use of L-statins and improved OS [overall surivival] (HR, 0.66) [hazard ratio], with a directionally consistent effect on BCSS [breast cancer specific survival] (SHR, 0.5). When examining statin intensity, high-intensity statin use had the strongest effect on OS among individuals with TNBC (HR, 0.25), with insufficient events to examine BCSS in this group.	In our analysis, we observed a strong association between new-onset statin therapy postdiagnosis and improved outcomes among individuals with TNBC. TNBC accounts for 10% to 20% of all breast cancer diagnoses and is associated with a poor prognosis because of the high rate of distant metastases, more limited effective treatment options, poor response rates, and poor treatment durability.31 Limited prior studies have investigated the association between statin therapy and outcomes in patients with TNBC. A recent institutional study in 869 patients with TNBC found a nonstatistically significant protective effect of statin use on the risk of death from breast cancer (relative risk, 0.70)
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812091	4.5	In this comprehensive cohort study, the inverse association between statin use and BC mortality was partly mediated by underlying cholesterol level. The risk decrease by statin use was clear only when the serum cholesterol level decreased simultaneously, although the subgroup analyses were limited by low statistical power. This finding suggests that serum cholesterol may be an important factor in BC and that the previously reported26 inverse association between statin use and BC mortality is likely mediated by underlying cholesterol level changes. Nevertheless, statin use after BC diagnosis was associated with a decreased risk for BC death even after adjustment for cholesterol level. The risk decreased further with increasing intensity of use, suggesting that statin use may affect estimated BC outcomes by mechanisms other than cholesterol reduction.	Inverse mortality association with statin use was observed in hormone receptor–positive cases but not in triple-negative cases. This finding suggests that hormone receptor positivity may have a role in the association between statins and BC. Tumor extent had a role, as the risk decrease was evident only in localized disease. In females with metastatic disease, the risk was conversely increased among statin users. Thus, statins may be beneficial only in females with early-stage BC. On the other hand, patients with metastatic disease have worse outcomes overall. It is plausible that interventions such as statins are unlikely to change the course of disease at this stage. Unlike postdiagnostic use, prediagnostic statin use was associated with elevated risk for both BC death and overall death in a non–dose-dependent manner. This finding suggests that prediagnostic use may not be a beneficial factor in BC but may instead reflect worse overall health
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00359-0/fulltext	4.5	During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) [nearly 30% lowered risk of CRC] ..The benefit for incident CRC was duration-dependent...: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 for 1 to <2 years of use, 0.46 for 2 to <5 years of use, and 0.38 for ≥5 years of use Compared with non-users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9 [nearly 2X lower]and all-cause mortality (IR: 156.4 vs. 231.4) [33%]	In this nationwide cohort, statin use was associated with a lower risk of incident CRC, CRC-related mortality, and all-cause mortality. The NNT to avoid one incident CRC, CRC-related death, and any death within 10 years after statin initiation was 227, 200, and 21, respectively. The benefits were duration-dependent, with a significantly lower risk after ≥2 years of use. The inverse association for incident CRC and CRC-related mortality were only observed in patients with UC, in patients diagnosed with IBD at age <50 years, in patients with longer IBD duration, for CRC-related mortality in colon cancer, and in early-stage CRC. The benefits for all-cause mortality were consistently observed regardless of sex, IBD subtype, age at IBD diagnosis, and disease duration, suggesting the benefits of using statin may apply to a broad at-risk population.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799080	4.5	Nineteen retrospective cohorts of 108 512 men (61 950 [57%] statin users) with more than 73 885 mortality events.. were included in a meta-analysus...Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 ) [Hazard Ratio] in random-effects meta-analysis	This systematic review and meta-analysis studied the association between statin use and survival outcomes in men using androgen-ablative therapies for advanced prostate cancer. In pooling data from 25 cohorts and 119 878 men, we identified an association of statin use with a 27% overall mortality and 35% PCSM benefit, albeit with significant interstudy heterogeneity. Subgroup analyses suggested a preferential advantage for men receiving ARATs. These findings were not driven by any single cohort, withstood robust sensitivity analyses, and were free of publication bias.
https://www.mdpi.com/2072-6694/12/8/2055	4.5	This study was controlled for the confounding effects of age, gender, urbanization, income, comorbidities, chemotherapy regimen, and other medicines. The study period was 1999–2008, and the follow-up time was until 31 December 2013. Our subpopulation analysis revealed that the use of statins reduced the mortality in these cohorts. The risk of the death for statin users and statin non-users was 37.6% and 61.0%, respectively, during the study period. After controlling for potential confounders, as the cumulative dose of statins increased a significant tendency towards reducing GC mortality was observed	The study cohort included 1835 patients with GC [Gastric Cancer] who had received therapies during the study period. The death numbers among statin users .. and statin non-users were 138 and 895, respectively. A dose–response association was noted between statin use and the OS [overall survival] of patients with GC after treatments. The adjusted hazard ratios were 0.62 and 0.34 for statin users ..., compared with non statin users
https://pmc.ncbi.nlm.nih.gov/articles/PMC6612541/	4.5	The median survival time differed between HCC patients who used statins after their cancer diagnosis (N=2293; 26.38 months, IQR, 14.82–47.41 months) and HCC patient who did not use statins post-diagnosis (N=13,129; 15.67 months, IQR, 7.58–30.68 months; p<0.0001) (Figure 1). For the primary analysis using a 3 month lag and time-varying multivariable models (Table 2), HCC patients who were post-diagnosis statin users had 15% lower risk of cancer specific mortality (adjusted HR, 0.85; 95% CI, 0.77–0.93) compared with non-users. Likewise, post-diagnosis statin use was associated with 11% lower risk of all-cause mortality (HR, 0.89; 95% CI, 0.83–0.95). However, we found no evidence for a dose-response relationship	Our findings suggest that statin use after cancer diagnosis is associated with lower mortality risk for patients with HCC. In the 3-month lagged analyses, we found that HCC patients who used statins after their cancer diagnosis date had 15% lower risk of cancer specific and 11% lower risk of all-cause mortality than HCC patients who did not use statins. The inverse association remained unchanged in a series of sensitivity analyses, including increasing the lag period to address the potential issue of selection bias. The possible protective effect inferred from the inverse association between statin use and cancer specific as well as overall mortality seems to be mostly related to post-HCC diagnosis statin use. While we found 11–15% lower risk of mortality for post-diagnosis statin users, there was no independent association between pre-diagnosis statin use and mortality risk in HCC patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168480/	4.5	In our study, patients treated with TDL [Thalidomide, Dexamethasone plus Lovastatin] regimen had significantly prolonged survival and overall survival (median PFS over 33 months and median OS over 49 months). These results suggest that the addition of LOV [Lovastatin] to THAL and DEX is safe and improves the response rate in patients with relapsed or refractory Multiple Myeloma, without hampering mobilisation efficacy and implementation of high-dose therapy. A future prospective randomised study is needed to confirm the value of LOV or other HMG-CoA reductase inhibitors in the treatment of MM patients.	In our study, 49 patients in the TDL group received LOV at a dose of 1 mg/kg (55 to 90 mg daily, median 65 mg daily) for 5 days and weekly for two consecutive weeks. Patients received a maintenance dose of 0.5 mg/kg for the next 2 weeks. We did not observe clinical or biochemical evidence of significant toxicity. Apathy and muscle weakness were observed in about 15% of the patients both in the TDL and TD groups. It is not clear whether they have been related to dexamethasone or lovastatin therapy. Results in the TDL group showed a significantly higher rate of very good responses (CR and NCR) and significantly shorter time to response in comparison to the TD-treated patients
https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-018-1066-z	4.5	For the association between use of statins, compared to no use, and BC-specific survival, the HR was estimated at 0.84 (ER+: HR = 0.95, ER−: HR = 0.77) An association with longer BC-specific survival was found among patients aged < 70 years, patients with regional disease and chemotherapy users. In addition, an indication of an association with longer BC-specific survival was found among the patients with TNBC (HR = 0.74)	We found evidence supporting an association between post-diagnostic use of statins and metformin and survival, in patients with BC. Our findings indicate potential differences according to ER status. HRs for use, compared to no use, were estimated at 0.96 (95% CI 0.85–1.08) for low-dose aspirin (ER+: HR = 0.97, 95% CI 0.83–1.13; ER−: HR = 0.97), 0.84 for statins (ER+: HR = 0.95, 95% CI 0.82–1.09; ER−: HR = 0.77), and 0.70 for metformin
https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-023-01697-2	4.5	A total of 26,190 patients were included. Of these 7591 (29%)...were post-diagnostic users of low-dose aspirin, statins, and metformin, respectively. The median follow-up was 6.1 years.. HRs [Hazard Ratios] for use, compared to no use, were estimated at 0.96 ( 0.84 [all breast cancers] for statins (ER+: HR = 0.95....ER−: HR = 0.77,	An association with longer BC-specific survival was found among patients aged < 70 years (HR = 0.82..), patients with regional disease (HR = 0.80.., and chemotherapy users (HR = 0.79). In addition, an indication of an association with longer BC-specific survival was found among the patients with TNBC (HR = 0.74).
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-5263-z	4.5	Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer related deaths (HR = 0.77) [Hazard Ratio]. Similarly, post-diagnostic statin use compared to non-use was associated with lower risk of breast cancer related deaths (HR = 0.83)	In conclusion, statin users, particularly simvastatin users, had a lower risk of breast cancer related deaths compared to non-users in this nationwide cohort of Swedish women with breast cancer diagnosed after the age of 40. Considering previous evidence from functional-, clinical- and epidemiological studies, this study adds evidence to the notion that statins seem to possess beneficial effects against breast cancer progression along with its cardiovascular benefits
https://www.ejcancer.com/article/S0959-8049(15)00922-3/abstract	4.5	We identified 4736 patients treated with sunitinib (n=1059), sorafenib (n=772), axitinib (n=896), temsirolimus (n=457), temsirolimus+interferon (IFN)-α (n=208), bevacizumab+temsirolimus (n=393), bevacizumab+IFN-α (n=391) or IFN-α (n=560), of whom 511 were statin users. Overall, statin users demonstrated an improved overall survival (OS) compared to non-users (25.6 versus 18.9 months, adjusted hazard ratio [aHR] 0.80	When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, aHR 0.749, 95% CI 0.584–0.961, p=0.023) or mammalian target of rapamycin (18.6 versus 14.0 months, aHR 0.657, 95% CI 0.445–0.972, p=0.035)
https://onlinelibrary.wiley.com/doi/10.1002/cnr2.1368	4.5	Both PFS and OS resulted as statistically relevant when the two groups were compared (median PFS 20.66 months in statin group vs 7.39 months in nonstatin group, P = .007, and median OS 23.44 months vs 9.13 months, respectively, P = .0063). This confirmed an advantage on survival parameters in the second-line setting with patients previously exposed to chemotherapy.	n our study, we demonstrated a significant relationship between improved PFS and OS and pre-existing statin use. Although interesting, this result needs to be validated with randomized clinical trials and larger cohorts (to select which type of patients could benefit the most with this pharmacological association). To date, many efforts have been made to ameliorate lung cancer patients prognosis and quality of life, even with the use of nonconventional anticancer drugs beside available therapies
https://journals.lww.com/ajg/abstract/2015/08000/impact_of_statin_use_on_survival_in_patients.23.aspx	4.5	The effects of statins varied by agent and dose. Active use of moderate-high-dose simvastatin at baseline was associated with improved overall and disease-free survival among patients undergoing resection for pancreatic cancer....Among 226 patients, 71 (31.4%) had prior simvastatin use and 27 (11.9%) had prior lovastatin use at baseline. Prior simvastatin but not lovastatin use was associated with improved survival.	n Cox regression, active simvastatin use was independently associated with reduced risk for mortality (adjusted hazard ratio (HR) 0.56) and risk for recurrence (adjusted HR 0.61). Survival improved significantly among patients who received moderate-high-intensity (median 42.1 months) doses compared with those who received low-intensity doses of simvastatin (median 14.1 months )
https://www.sciencedirect.com/science/article/abs/pii/S0959804920313186	4.5	Altogether, our results showed that statin use is associated with improved clinical activity in thoracic cancer patients receiving PD-1 inhibitors in an intensity-dependent manner, whether statin use reflects a general prognostic association or is causatively linked with improved clinical activity of PD-1 inhibitors still needs to be assessed within randomized trials. If our results were prospectively confirmed, statins could represent an optimal strategy of drug repurposing	This study reports that baseline statin use was associated with improved clinical activity of PD-1 inhibitors in MPM and aNSCLC patients. This association resulted to be intensity-dependent, as use of high-intensity but not of low/moderate-statins led to better outcomes. The mechanism by which statins might boost clinical activity of PD-1 inhibitors in cancer is a matter of study [11]. Preliminary evidences suggested that blocking the MVA pathway might have a direct antitumor effect
https://pmc.ncbi.nlm.nih.gov/articles/PMC10473877/	4	Statin therapy produces significant benefits on overall survival and cancer-specific survival. Although the benefits might be lower than the approved immunotherapy medications, its cost-effectiveness could lead to dramatic health consequences. Concomitant use of statin drugs as cancer treatments is highly recommended in future clinical trials.	Finally, because metastases at distant sites rather than the primary tumors cause the majority of patients’ death (62), inhibition of metastasis by statins accounts important for the inverse association that we observed between statin use and the mortality of advanced-stage cancer. It was reported that the depletion of GGPP by statins blocks posttranslational modification of multiple small GTPase proteins to localize to the membrane. These small GTPase proteins such as RhoA, Ras and Rac are involved in cell migration and tumor invasiveness
https://pmc.ncbi.nlm.nih.gov/articles/PMC6330431/	4	Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer related deaths (HR = 0.77; 95% CI 0.63–0.95, P = 0.014). Similarly, post-diagnostic statin use compared to non-use was associated with lower risk of breast cancer related deaths (HR = 0.83)	This large-scaled nationwide Swedish study demonstrates that the use of cholesterol-lowering statins is associated with lower risk of breast cancer related and overall deaths among women diagnosed with breast cancer, irrespective of whether statins were used pre- or post-diagnosis. These results confirm previously presented studies based on Scandinavian cohorts [4, 5, 9] although the results have been less evident in studies from England, Ireland, and Scotland. The background for these disparities is not know
https://www.nature.com/articles/s41598-023-45958-8	4	In our population-based cohort consisting of 1,169 men initiating ADT during the follow-up, inverse association between statin use and the risk of developing CRPC was observed. This finding is in line with previous studies detecting statins might be linked to improved prostate cancer prognosis among ADT treated patients. In our cohort, we did not observe statistically significant improvement by statin use in survival of CRPC patients. These results are suggestive that optimal timing of repurposing statins on prostate cancer treatment is concurrently with androgen deprivation therapy	Our results support previous epidemiological studies showing statin use may improve survival in concurrent use with ADT and suggest better PCa-specific survival among statin users to be explained by longer time to development of castration-resistant prostate cancer. Considering the main results of this study and the results of previous studies assessing the prognosis of PCa patients by statin use, we suggest the optimal time window for statin use to be concurrently with androgen deprivation therapy. Therefore, future trials assessing the benefit of statin use in PCa prognosis should focus especially on that period when plenty of quality life years can still be saved.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5540782/	4	Our findings suggest potential benefits of statins on improving survival among elderly PDAC [pancreas] patients...Statin use was significantly associated with improved overall survival hazard ratio (HR), 0.94, and survival was more pronounced in post-diagnosis statin users (HR, 0.69)	We observed that statin use was significantly associated with improved overall survival of elderly PDAC patients, and this finding was more pronounced in post-diagnosis statin users. A retrospective study that included 1,761 newly diagnosed PDAC patients found that statin use was significantly associated with a lower mortality using a time-dependent Cox model (HR, 0.78)
https://www.sciencedirect.com/science/article/abs/pii/S104366181831870X?via%3Dihub	4	On the basis of our meta-analysis involving 99,297 lung cancer patients, we found that statin exposure was associated with a 21%, 17% and 15% reduced risk of all-cause mortality, lung cancer-specific mortality and risk of recurrence, respectively. The survival benefits were maintained in subgroup analyses by study setting, region, study centre, sample size and disease stage for OS	statin users after diagnosis of lung cancer had more survival benefit for OS (HR 0.68) than those before diagnosis (HR 0.86) and current users (HR 0.79). Besides, statin users were likely to have more survival benefits in stage IV lung cancer patients (HR 0.77, 95% CI 0.74–0.79) than in mixed stage (I–IV or I–III) patients Statin exposure is associated with significantly improved survival in patients with lung cancer.
https://www.nature.com/articles/bjc2016149	4	Current statin use was associated with lower risk of cancer death compared with never-use (HR, 0.78; 95% CI, 0.71–0.86; P<0.001; Figure 1), and lower risk of all-cause mortality (HR, 0.80; 95% CI, 0.74–0.88). The lower risk of cancer death associated with statin use did not depend on statin potency	In this prospective cohort study, we found that current statin use in postmenopausal women with cancer was associated with lower risk of cancer death. Use of other lipid-lowering medications was also associated with a lower risk of cancer death; this finding suggests that a reduction in circulating cholesterol levels may mediate increased cancer survival. However, a dose–response relationship was not found, suggesting that results should be interpreted cautiously. Multiple molecular mechanisms have been linked to statins and cancer, including the mevalonate pathway
https://www.nejm.org/doi/full/10.1056/NEJMoa043792	4	Our data indicate that there is a strong inverse association between the risk of colorectal cancer and the long-term use of statins. This association is consistent with preclinical data suggesting that it is biologically plausible that statins may have a role in colorectal cancer, as well as with evidence from secondary analyses of some, but not all, randomized, controlled trials. These data are also consistent with the results of a small, nested case–control study from Quebec, Canada, that reported a significant reduction in the occurrence of all cancers among statin users as compared with persons who did not use statins	We found that the use of statins is associated with a 47 percent relative reduction in the risk of colorectal cancer after adjustment for other known risk factors and is specific to this class of lipid-lowering agents. Our finding suggests that statins deserve further investigation in chemoprevention and therapeutic clinical trials.
https://ascopubs.org/doi/full/10.1200/JCO.2013.49.4757	4	During a mean follow-up time of 4.4 years, 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76) and all-cause mortality (HR, 0.86) These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55 and HR, 0.66), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82	Use of statins after prostate cancer diagnosis was associated with a 24% risk reduction in prostate cancer mortality (Table 2). A dose-response relationship was observed in terms of cumulative duration of use and dose, with the HRs becoming progressively more protective with longer durations of use and higher cumulative doses (≥ 36 months of use: HR, 0.61; 95% CI, 0.49 to 0.75; and ≥ 1,096 DDDs: HR, 0.57; 95% CI, 0.46 to 0.72). In an exploratory analysis, a 23% decreased risk was observed with lipophilic statins, and a 35% decreased risk was observed with hydrophilic statins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147735/	4	Of the 14,976 women included in analyses, 27% used a statin after diagnosis and the median follow up time was 4.51 years. Statin use (vs non-use) was associated with a statistically significant decreased risk of BCD (adjusted hazard ratio: 0.74; 0.63–0.86). The association was attenuated when considering a subgroup of ‘new’ statin users (HR: 0.91; 0.69–1.19), however other analyses revealed that the protective effect of statins was more pronounced in estrogen receptor positive patients (HR: 0.77), postmenopausal women (HR: 0.74), and in women with advanced stage disease (HR: 0.65).	In this study, statin use was associated with a statistically significant decreased risk of breast cancer death, with subgroup analyses revealing a more protective effect in ER+ patients, postmenopausal women, and in women with advanced stage disease. Further research is warranted to determine if these associations are replicated in other clinical settings.
https://www.cell.com/iscience/fulltext/S2589-0042(24)01905-9	4	Lipid-lowering drug use was defined as new users before enrollment and the primary outcome was cancer incidence. The Cox proportional hazards regression model was used to evaluate the association between drug use and outcome. We also performed a meta-analysis. We found that lipid-lowering drugs were associated with decreased risk of 21 types of cancers, including melanoma, skin cancer, and reproductive, hematological, urinary, digestive, nervous, and endocrine system cancers (all p < 0.0010). Our meta-analysis documented that lipid-lowering drugs reduced the risk of prostate, liver, and gastric cancers, especially (all p < 0.050). Overall, lipid-lowering drugs had protective associations with cancer incidence, suggesting the possible cancer prevention effects even in the general population	Based on UK Biobank, we observed that the use of lipid-lowering drugs, particularly statins, was associated with reduced risk of melanoma, skin cancer, and reproductive (prostate, ovarian, uterus, cervical, breast), hematological (leukemia, lymphoma, multiple myeloma), urinary (bladder, kidney), digestive (esophagus, gastric, intestinal, colorectal, liver), respiratory (lung), nervous (brain cancer), endocrine system (thyroid, pancreatic) cancers even in patients with hyperlipidemia. Our meta-analysis documented that lipid-lowering drugs reduced the risk of prostate, liver, and gastric cancer, especially. According to our findings, lipid-lowering drugs reduced the overall risk of cancer death
https://pmc.ncbi.nlm.nih.gov/articles/PMC4522645/	4	A total of 1043 patients used GLDs before CRC diagnosis; 666 (64%) used metformin, 639 (61%) used statins and 490 (47%) used aspirin after CRC diagnosis. Multivariable analyses revealed that longer cumulative exposure to metformin was not associated with overall mortality (HRCumulative exposure/6 months 1.02), whereas the favourable effect of statins increased with cumulative exposure (HRCumulative exposure/6 months 0.93). No association between aspirin use and overall mortality was seen (HRCumulative exposure/6 months 0.98)	This population-based study revealed that among CRC patients who started using GLDs before cancer diagnosis, cumulative exposure to metformin or aspirin was not associated with overall mortality. However, longer cumulative exposure to statins was independently associated with lower overall mortality, suggesting a drug effect of statins in CRC patients with diabetes
https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.15851	4	The magnitude of observed tumour response in our study was subtle, with ‘flattening’ of PSA velocity following a short course of statin treatment observed in six of 12 evaluable patients. Our primary objective was to investigate whether we could detect any evidence of statin‐mediated tumoral effects based on PSA measurements. In hindsight, for a proof‐of‐concept study, the criteria of tumour response with a ≥50% drop in serum PSA levels can be considered overambitious, given the fact that, at a population level, the association between statin treatment and favourable patient outcome typically requires a sustained period of statin treatment	In summary, our proof‐of‐concept study revealed data suggestive of stabilization of CRPC within a 6‐week study period. Given the current treatment options for second‐ and third‐line androgen receptor pathway inhibitors, we found that, for patients with advanced CRPC, both oncologists and patients favoured the commencement of standard of care treatment rather than taking part in the SPECTRE study. Hence, the design of future studies may incorporate the use of statins with one of the androgen receptor pathway inhibitors
https://pubmed.ncbi.nlm.nih.gov/26687834/	3.5	We demonstrate that statin use may be associated with improved survival in patients with mRCC treated in the targeted therapy era. Statins could represent an adjunct therapy for patients with mRCC; however, this is hypothesis generating and requires prospective evaluation.	..statin users demonstrated an improved overall survival (OS) compared to non-users (25.6 versus 18.9 months, adjusted hazard ratio [aHR] 0.80. When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, aHR 0.749, 95% CI 0.584–0.961, p = 0.023) or mammalian target of rapamycin (18.6 versus 14.0 months, aHR 0.657)
https://pubmed.ncbi.nlm.nih.gov/20698078/	3.5	These data indicate statin use in patients diagnosed with epithelial ovarian cancer is associated with improved survival, and suggest a potential suppressive impact of HMG-CoA reductase inhibitors on tumor biology. Studies are proposed to explore the molecular mechanisms underlying these clinical observations.	Median progression-free survival for statin users was 24 months, compared to 16 months for statin non-users (p=0.007). Similarly, overall survival was significantly longer for statin users (62 months) compared to statin non-users (46 months, p=0.04). Multivariable analysis identified statin use as an independent positive prognostic factor,
https://www.nature.com/articles/s41598-024-53252-4	3.5	During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11–0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03–2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers	In this study, the significant effect of the long-term use of anti-cholesterol drugs on the increased risk of pancreatic cancer was observed in the > 5 y group especially in all of the total, men, and women. A previous study reported the association between the use of statins for less than 5 years and an increased risk of pancreatic cancer 25 and a study using data mining also reported the statin use increased pancreatic cancer risk 26. However, most previous reports suggested that statins have a protective effect in decreasing pancreatic cancer risk
https://www.tandfonline.com/doi/full/10.1080/0284186X.2016.1223882	3.5	A recent meta-analysis of randomized trials studying the effect of statins on established ED was reported [Citation6]. Eleven studies met the inclusion criteria for the analysis, totaling 713 patients. The most commonly utilized drug was atorvastatin. The median duration of follow-up was only three months. This analysis revealed a statistically significant and clinically relevant improvement in IIEF score by 3.4 points. This magnitude of improvement is about one third to one half of that seen with PDE5 inhibitors	Also, the drug utilized in the present study, lovastatin, is not very lipophilic, and other statins such as atorvastatin might be more suitable. Nevertheless, the results are intriguing, given that about one third of men report poor sexual functioning at 24 months after radiation [Citation1]. The results of the present study suggest that statins should be studied further as a potential means to prevent radiation-induced ED.
https://pubmed.ncbi.nlm.nih.gov/35780525/	3.5	Our study suggests a prognostic impact of statin use in patients receiving nivolumab for mRCC. (kidney cancer)...Stratified by age, longer median OS and PFS were associated with statin exposure in both patients aged ≥70 y (median OS: 21.4 versus 10.1 months, median PFS: 16.4 versus 4.6 months, p = 0.022) and <70 y (median OS: 34.4 versus 21.4 months; median PFS: 10.3 versus 4.6 months	Medical records of patients with documented mRCC treated with second- or third-line nivolumab were reviewed at ten institutions from Italy, Spain and the USA. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit. Univariate and multivariate analyses were used to explore the association of variables of interest with survival.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2804095	3.5	Compared with nonusers, statin users had a significantly lower risk of all-cause death (adjusted hazard ratio [HR], 0.83). Notably, the risk reduction was mainly attributed to cancer-related death (adjusted HR, 0.83). Only a small number of patients died of cardiovascular causes, and the ratios were similar between statin users and nonusers. No significant differences were observed in cardiovascular outcomes, including heart failure and arterial and venous events, between statin users and nonusers. Using a time-dependent analysis, statin users also presented a significantly lower risk of cancer-related death (adjusted HR, 0.28)	In this nationwide cohort, we found that among patients with breast cancer, the use of statins was associated with a significant risk reduction of cancer-related deaths. In contrast, cardiovascular outcomes were not significantly different between statin users and nonusers. Statins are known to suppress atherosclerosis and improve cardiovascular outcomes.4,14,15 In a retrospective cohort study, Abdel-Qadir et al16 reported that statin exposure lowered the risk of hospitalization for HF in women with breast cancer aged 66 years or older. It has been speculated that patients prescribed statins have a high prevalence of preexisting coronary heart disease and face excess cardiac risks. However, in our cohort focusing on Asian patients with breast cancer, who were relatively younger at diagnosis, only 5% to 7% of the patients had underlying vascular diseases. On the other hand, statins have received special attention for their pleiotropic effects, including anti-inflammatory and antitumor potential
https://onlinelibrary.wiley.com/doi/10.1002/ctm2.726	3	..statin intake correlated with a significant reduction in cancer incidence (odds ratio [OR], .72) For statin-taking patients, we calculated a higher cancer survival probability versus subjects not taking any statins (hazards ratio [HR], .64) We found no difference for low-dose versus high-dose treatments. When considering each statin separately, we found a strong cancer-preventive effect for atorvastatin (OR, .41) and significant effects for fluvastatin (OR, .7), pravastatin (OR, .63) and rosuvastatin (OR, .43); simvastatin showed only a weak cancer-preventive effect (OR, .9), and lovastatin effects were not readily assessed	The chemopreventive influence of simvastatin (OR .63, ) and atorvastatin (OR .3) correlates with their capacity to reduce MACC1 expression ... our study revealed strong evidence for cancer-preventive effects of statins in a large trans-Atlantic cohort, comprised of long-term statin users. We link this beneficial effect to MACC1 transcriptional inhibition, yielding inhibited tumour growth and metastasis formation. These two lines of evidence suggest statin use in treating cancers, for which MACC1 serves as a predictive biomarker and interventional target necessitating prospective, randomized clinical trials.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087110/	3	Our pilot study suggests that statins have biologic effects on the high grade subset of early stage breast cancers. Fluvastatin decreased tumor proliferation and increased apoptosis in these tumors, results that are concordant with the mechanism of action of statins and the results from preclinical experiments and some epidemiologic studies. Our findings also support further investigation of lipophilic statins as potential agents to prevent progression in high grade disease. Given its aggressive nature, greatest sensitivity to lipophilic statins, the lack of alternative interventions, and the safety and health promoting benefits of statins, we can ill afford to miss the opportunity to assess the effect of statins to prevent high grade breast cancer.	we observed biologic activity on cholesterol, proliferation, and apoptosis. Effects were significant in high grade DCIS, not just ER-negative patients, although the small numbers of patients with paired samples may be a limiting factor. Seventy-three percent of the high grade lesions were ER-negative, however, four subjects with ER-positive high grade DCIS had significant changes in both Ki-67 and CC3, suggesting that other factors such as proliferation may determine sensitivity to statins. Moving forward, it would seem most appropriate to target high grade DCIS patients for a trial of statin impact, and to further stratify on ER status to better resolve the question of whether grade or ER status is the more appropriate criteria for patient selection.
https://www.mdpi.com/2072-6694/15/12/3093	2	Our data indicate considerable benefits regarding the survival probability for HNC [head and neck cancer] patients with statin medication compared to HNC patients without statin medication.	ur findings provide first clinical data on statin use and the prognostic value in HNC in a large cohort, and lead to the conclusion that statin use in HNC patients correlates with higher five-year survival. These findings support previous studies on the relationship between statin use and HNC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417177/	1	Given the evidence from retrospective studies and the strong rationale provided by laboratory studies in cells and tumor models, there is a compelling argument for randomized trials of concomitant treatment with lipophilic statins and radiotherapy in head and neck cancer, selecting patients with no history of treatment with statins for cardiovascular disease. To obtain the full benefits of statins, initiating treatment upon cancer diagnosis and then continuing for a prolonged course may be necessary. This may have the dual advantage of increasing the efficacy of radiotherapy but also reducing late side effects such as increased stroke risk.	Regarding prevention, while multiple studies have suggested reduced risk of cancer, including HNC with long-term statin use, this is not a strong effect, and a recent case-control study found that prior exposure to statins in HNC patients is not associated with lower cancer risk ..Meta-analyses have revealed statin use may contribute to lowering the incidence of specific cancers such as hepatocellular carcinoma (HCC), though umbrella reviews surveying multiple cancer types identified overall weak evidence for benefits on incidence or survival , pointing to considerable variability among cancer si
https://jeccr.biomedcentral.com/articles/10.1186/s13046-021-02041-2	1	However, the value of statins as therapeutic agents against cancer in humans remains an area of active research. Although the clinical evidence that supports the use of statins as a monotherapy for cancer is not convincing, several preclinical and clinical studies indicate that statins potentiate the effects of currently used cancer therapies when administered in combination. Furthermore, statins have been shown to address the shortcomings and side-effects caused by anticancer agents. Nevertheless, difficulties in statin administration at high doses remain unsolved, so satins are currently unlikely to be prescribed as a monotherapy. Therefore, we advocate the use of statins as an adjuvant therapy for cancer	A meta-analysis of 1,111,407 cancer patients showed that the use of statins reduced all-cause mortality and cancer-specific mortality by 30% and 40%, respectively [58]. Recently, a study involving 303 patients with advanced pancreatic cancer showed that the use of statins (simvastatin and atorvastatin) was associated with increased overall survival in patients [62]. In addition, in patients receiving radiotherapy, surgery and chemotherapy for advanced pancreatic cancer, statin treatment was associated with a 2-year increase in survival, suggesting that statins help improve the outcome of interventions for advanced pancreatic cancer [63]. A meta-analysis of breast cancer studies showed that the overall use of statins was associated with lower cancer-specific and all-cause mortality.
https://www.nature.com/articles/s41416-018-0267-7	1	We demonstrate that statins can directly affect the proliferation of breast cancer cells, specifically at the metastatic site. In a 2D co-culture model of breast cancer cell interaction with the liver, we demonstrate that atorvastatin can directly suppress proliferation of mesenchymal but not epithelial breast cancer cells. Further, in an ex vivo 3D liver microphysiological system of breast cancer metastasis, we found that atorvastatin can block stimulated emergence of dormant breast cancer cells. In two independent models of spontaneous breast cancer metastasis to the liver and to the lung, we find that statins significantly reduce proliferation of the metastatic but not primary tumor cells.....As statins can block metastatic tumor outgrowth, they should be considered for use as long-term adjuvant drugs to delay clinical emergence and decrease mortality in breast cancer patients	We found the primary tumor size did not significantly change with atorvastatin treatment (Fig. 6d). Primary tumors were marked by central regions of necrosis (Fig. 6c). Primary tumor proliferation was quantified by assessing the Ki-67 positivity of the peripheral zone of the tumor. The proliferation of the primary tumor was not significantly affected by atorvastatin treatment (Fig. 6e, f). In contrast to the primary tumor, the lung metastases were much smaller and exhibited no necrotic regions (Fig. 6g). Moreover, we found that atorvastatin reduced the proliferation of lung metastases in a dose-dependent manner, though this trend did not reach statistical significance in the small number of animals challenged
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359995/	1	Inhibition of cholesterol uptake has shown anti-cancer property in some cases, for examples, using shRNA for LDLR increases the efficacy of gemcitabine in pancreatic cancer (Guillaumond et al., 2015); an FDA approved cholesterol uptake blocker ezetimibe retards in vivo prostate cancer progression by inhibiting angiogenesis (Solomon et al., 2009). Therefore, combination of statins and cholesterol uptake blocker may provide enhanced anti-cancer effect, which warrants more in-depth studies. It is currently difficult to predict the type of cancers that particularly sensitive to statin therapy. However, encouraging results from some trials (Garwood et al., 2010; Bjarnadottir et al., 2013; Harshman et al., 2015) suggest that patients with hormone-dependent cancers, such as breast cancer and prostate cancer, may benefit from adding statins to their treatment. This may be partly because cholesterol is the precursor of hormones such as oestrogen and androgens, which have a major role in the development of these cancers (Finlay-Schultz and Sartorius, 2015). Clinical trials are required to further define the subset of cancers that are more statin-sensitive (Mullen et al., 2016).	Accumulating pre-clinical and clinical trials of statins in different cancers suggested overall beneficial role of statins with a favorable safety profile in cancer treatment and prevention. The anti-cancer effects, as well as their well-tolerance, low cost, and much lower toxicity compared with the conventional chemotherapy drugs, attract increasing consideration of repurposing statins as a promising strategy for cancer treatments. Beyond de novo cholesterol biosynthesis, most cells can acquire cholesterol via uptake extracellular cholesterol by various molecules including LDLR. Therefore, cancer cells may bypass their dependency on de novo cholesterol biosynthesis by relying on exogenous cholesterol, such as LDL/HDL, which limits the anti-cancer effect of statin treatmen
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640221/	1	Our results suggest that the clinical benefit of statin treatment in early diagnosed or resected cancer patients could be driven by a reduction in the formation of new metastases due to inhibition of MET. In addition, the statin-induced mesenchymal cell state is reversible and persists only as long as statins are present. From a therapeutic standpoint, it is important that chronic statin treatment is generally well-tolerated in patients even at high doses (De Angelis, 2004).... In addition, beneficial off-target effects of statins have been described, although the causes are still unclear, including improved endothelial function, increased plaque stability, antithrombotic and anti-inflammatory effects, reduced risk of dementia and Alzheimer disease, and reduced ischemic stroke (Murphy et al., 2020). Therefore, this class of drugs is well-suited for continuous therapy, which would be required to block the development of metastases in patients with resected tumors or early metastasis.	The concept that cancer cells need to undergo EMT in order to metastasize and that mesenchymal cancer cells are more metastatic is broadly known (Massagué and Obenauf, 2016; Steeg, 2006; Fares et al., 2020). However, several studies have shown reduced metastatic ability in cancer cells subjected to statin treatment (Beckwitt et al., 2018; Yang et al., 2017). We confirmed these findings in mice, showing that established tumors develop fewer metastases when the mice are treated with statins (Figures 1F–1H). A closer look at our data points to a resolution of these initially counterintuitive findings. We hypothesized that the statin-induced cellular state leads to a reduction in cellular plasticity that plays a significant role in the metastatic transition of a cancer cell, as the cancer cells need to revert back to an epithelial phenotype once they have reached the secondary site in order to form metastases. Indeed, cancer cells that were treated with statins showed a significant reduction in colony formation, and this effect was even more pronounced when the cells were additionally pretreated with statins before seeding

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