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

Abstract

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.

De novo cholesterol biosynthesis: an additional therapeutic target for the treatment of postmenopausal breast cancer with excessive adipose tissue

“…Last but not least, the statins-metform in association could be the winning strategy also in preventing cancer development in healthy women with high mammographic breast density, that is, women whose breasts have a high stroma component often associated with the infiltration of aromatase-overexpressing macrophages, and for this reason at risk of developing breast cancer. Indeed, as demonstrated in a recent study [ 60 ], metformin use was associated with a decreased percentage of the dense area and an increase in non-dense areas compared to non-metformin users.…”

Repurposing of atorvastatin and metformin denotes their individual and combined antiproliferative effects in non‐small cell lung cancer

“…Despite the limited availability of clinical data supporting the use of statins or Met as monotherapy for cancer management, numerous investigations have evidenced their enhancing role with traditional chemotherapy [17]. Also, their beneficial combined effect was reported in many human disorders (exemplified in Table 4 [34][35][36][37][38][39][40][41][42][43][44][45]). Herein, we thought to explore the combined anticancer potentials of Ator and Met in NSCLC cells, since this combination is widely prescribed for hyperglycemic/hyperlipidemic conditions.…”

Breast cancer worry, uncertainty, and perceived risk following breast density notification in a longitudinal mammography screening cohort

“…The New York Mammographic Density (NY MaDe) Study is a study of breast cancer risk factors and screening in a mammography cohort of women in Northern Manhattan, New York City, and has been previously described [ 13 , 16 , 17 ]. Between 2016 and 2018, we recruited 812 women, ages 40–60 years, during their screening mammography appointment at a clinic in Northern Manhattan.…”