Association of antidiabetic medication and statins with breast cancer incidence in women with type 2 diabetes

Hosio, Mayu; Urpilainen, Elina; Marttila, Mikko; Hautakoski, Ari; Arffman, Martti; Sund, Reijo; Puistola, Ulla; Läärä, Esa; Jukkola, Arja; Karihtala, Peeter

doi:10.1007/s10549-019-05185-0

Cited by 14 publications

(15 citation statements)

References 44 publications

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“…And the findings from several observational studies regarding the association between statins use and breast cancer are inconsistent. Murakami et al reported that statin use is inversely associated with the risk of breast cancer [16], while Leung et al showed the opposite finding [17], furthermore some studies found no associations [18,19]. The findings regarding the relationship between statins and the prognosis of breast cancer are also conflicting.…”

Section: Introductionmentioning

confidence: 99%

Effect of statins use on risk and prognosis of breast cancer: a meta-analysis

Zhao

Ji²,

Ye³

et al. 2021

Anti-Cancer Drugs

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The findings regarding the association between statins use and breast cancer are inconsistent. Given the widely and long-term use of statins as first choice drug for dyslipidemia, we conducted this meta-analysis for better understanding the associations between statins use and the risk and prognosis of breast cancer. Articles regarding effect of statins use on risk, prognosis of breast cancer and published before January 2021 were searched in the following databases: Web of Science, PubMed, EMBASE, Medline and Google Scholar. Odds ratios (ORs)/ relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI. The meta-analysis showed no significant association between statins use and risk of breast cancer (OR/RR = 1.02; 95% CI, 0.97-1.08; I 2 = 76.1%; P < 0.001). The meta-analysis showed that statins use was associated with lower breast cancer recurrence, all-cause mortality and disease-specific mortality (breast cancer recurrence: HR = 0.75; 95% CI, 0.67-0.84; I 2 = 31.7%; P = 0.154; all-cause mortality: HR = 0.82; 95% CI, 0.77-0.89; I 2 = 67.5%; P < 0.001; and disease-specific mortality: HR = 0.82; 95% CI, 0.72-0.93; I 2 = 83.6%; P < 0.001). Overall, in this report we demonstrated that the use of statins can improve the prognosis of breast cancer patients including lower risks of breast cancer recurrence, all-cause and cancer-specific mortality, though statins therapy may not have an impact on reducing the risk of breast cancer. Anti-Cancer Drugs 33: e507-e518

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Section: Introductionmentioning

confidence: 99%

Effect of statins use on risk and prognosis of breast cancer: a meta-analysis

Zhao

Ji²,

Ye³

et al. 2021

Anti-Cancer Drugs

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“…According to data from the Finnish national diabetes database, 2300 women were diagnosed with BC, and then were treated with metformin, insulin and statins. Case-control analysis clearly showed that there was no difference in cancer incidence between the metformin group (HR = 1.02, 95% CI 0.93-1.11) and the statin group (HR = 0.97, 95% CI 0.89-1.05), while insulin treatment was associated with slightly increased morbidity (HR = 1.18, 95% CI 1.03-1.36) [48].…”

Section: Breast Cancermentioning

confidence: 96%

“…Likewise, research indicates a reduction in morbidity, as well as a more favorable clinical course as a result of the application of drugs, such as metformin, which reduce these factors [58][59][60]. However, the results of the studies on the use of statins in EC remain inconclusive [61][62][63][64][65], and the observational studies often compare the effects of two drugs, i.e., antidiabetic metformin and a selected compound from the statins class [48,49].…”

Section: Endometrial Cancermentioning

confidence: 99%

Statins: HMG-CoA Reductase Inhibitors as Potential Anticancer Agents against Malignant Neoplasms in Women

et al. 2020

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Statins, also known as HMG-CoA inhibitors, are a class of bioactive small molecules that efficiently reduce the levels of cholesterol, and therefore are commonly used to manage and prevent various cardiovascular diseases. With respect to their original medical indications, statins are currently in the group of the most prescribed drugs worldwide. Of note is that statins are perceived actually rather as agents that have pleiotropic activities; in addition to their inhibitory activity on the production of endogenous cholesterol. Statins may also affect cell proliferation, angiogenesis and/or migration (metastasis) of different cancer cells, and play a positive role in the chemoprevention of cancer, thus being the excellent candidates to be repurposed in oncology. Particularly intriguing in this context seems to be the promising role of statins on both the incidence and course of common malignant neoplasms in women. In this article, we review and discuss the effect of the use of statins in the treatment of three types of cancer, i.e., breast, endometrial and ovarian cancer, with the highest mortality among gynecological cancers.

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“…Well-tolerated, commonly used medications for multiple chronic conditions with potential for reducing cancer risk may offer more widespread and sustained use [3][4][5][6]. Metformin, a biguanide used to treat type 2 diabetes, has antiproliferative effects, has been linked to reduced cell growth and circulating estrogen, and has been recommended to reduce the risk of breast cancer recurrence though the evidence is less consistent for incidence [7][8][9][10][11][12][13]. The evidence for statins, HMG-CoA reductase inhibitors used to treat high cholesterol that may reduce the cholesterol available for hormone synthesis and cell proliferation, is stronger but similarly more consistent for recurrence than incidence, and particularly congruous for lipophilic statins [7,[14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

“…Metformin, a biguanide used to treat type 2 diabetes, has antiproliferative effects, has been linked to reduced cell growth and circulating estrogen, and has been recommended to reduce the risk of breast cancer recurrence though the evidence is less consistent for incidence [ 7 – 13 ]. The evidence for statins, HMG-CoA reductase inhibitors used to treat high cholesterol that may reduce the cholesterol available for hormone synthesis and cell proliferation, is stronger but similarly more consistent for recurrence than incidence, and particularly congruous for lipophilic statins [ 7 , 14 – 19 ]. Little is known about the combined use of these drugs and breast cancer risk, though combined use can be common in individuals with type 2 diabetes who are at higher risk for cardiovascular disease [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density

et al. 2020

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Background Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. Methods Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40–61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported “ever” use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. Results We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (β = − 6.56, 95% CI = − 9.05 to − 4.06), and dense area (DA) (β = − 9.05, 95% CI = − 14.89 to − 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., β = − 6.86, 95% CI: − 9.67, − 4.05 and β = − 7.07, 95% CI: − 10.97, − 3.17, respectively, for PD) and higher NDA (β = 25.05, 95% CI: 14.06, 36.03; β = 29.76, 95% CI: 14.55, 44.96, respectively). Conclusions Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease.

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Association of antidiabetic medication and statins with breast cancer incidence in women with type 2 diabetes

Cited by 14 publications

References 44 publications

Effect of statins use on risk and prognosis of breast cancer: a meta-analysis

Effect of statins use on risk and prognosis of breast cancer: a meta-analysis

Statins: HMG-CoA Reductase Inhibitors as Potential Anticancer Agents against Malignant Neoplasms in Women

Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density

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