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

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Erica J. Lee Argov ◽  
Teofilia Acheampong ◽  
Mary Beth Terry ◽  
Carmen B. Rodriguez ◽  
Mariangela Agovino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Density ◽  
Menopausal Status ◽  
Mammographic Breast Density ◽  
Age At First Birth ◽  
Dense Area ◽  
Cross Sectional ◽  
Statin Use

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.

scholarly journals Is Mammographic Breast Density an Endophenotype for Breast Cancer?

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3916
Author(s):  
Ellie Darcey ◽  
Nina McCarthy ◽  
Eric K. Moses ◽  
Christobel Saunders ◽  
Gemma Cadby ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Density ◽  
Disease Risk ◽  
Health Study ◽  
Mammographic Breast Density ◽  
Dense Area ◽  
Cross Sectional ◽  
Meta Analyses

Mammographic breast density (MBD) is a strong and highly heritable predictor of breast cancer risk and a biomarker for the disease. This study systematically assesses MBD as an endophenotype for breast cancer—a quantitative trait that is heritable and genetically correlated with disease risk. Using data from the family-based kConFab Study and the 1994/1995 cross-sectional Busselton Health Study, participants were divided into three status groups—cases, relatives of cases and controls. Participant’s mammograms were used to measure absolute dense area (DA) and percentage dense area (PDA). To address each endophenotype criterion, linear mixed models and heritability analysis were conducted. Both measures of MBD were significantly associated with breast cancer risk in two independent samples. These measures were also highly heritable. Meta-analyses of both studies showed that MBD measures were higher in cases compared to relatives (β = 0.48, 95% CI = 0.10, 0.86 and β = 0.41, 95% CI = 0.06, 0.78 for DA and PDA, respectively) and in relatives compared to controls (β = 0.16, 95% CI = −0.24, 0.56 and β = 0.16, 95% CI = −0.21, 0.53 for DA and PDA, respectively). This study formally demonstrates, for the first time, that MBD is an endophenotype for breast cancer.

Gene methylation in random FNA samples as biomarkers for breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 518-518
Author(s):  
Vered Stearns ◽  
Seema Ahsan Khan ◽  
Mary Jo Fackler ◽  
Robert T. Chatterton ◽  
Lisa K. Jacobs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Density ◽  
Menopausal Status ◽  
Life Time ◽  
Wilcoxon Test ◽  
Mammographic Breast Density ◽  
Gene Methylation ◽  
Cytologic Atypia

518 Background: Current methods to determine breast cancer risk are insufficiently sensitive to select women most likely to benefit from preventive strategies. We hypothesized that candidate gene promoter hypermethylation may provide an individualized risk profile. We performed a prospective study to determine whether DNA cumulative methylation index (CMI) varies by menstrual phase or menopausal status, and to correlate CMI with established risk factors. Methods: We obtained random fine needle aspiration (rFNA) samples from healthy women age 35-60 and determined their menopausal and menstrual status, lifetime Gail risk, mammographic breast density, and cytologic atypia assessed as the Masood score. We evaluated CMI of 11 candidate genes in rFNA cells using the Quantitative Multiplex Methylation-Specific PCR (QM-MSP) technique. We used Wilcoxon test and ANOVA model to compare CMI across menopausal and menstrual (follicular, mid-cycle, luteal) categories, respectively. We used linear regression model to adjust for age and BMI. Methylation scores were log-transformed in the analysis. Results: We enrolled 390 women at the Avon Breast Centers at Johns Hopkins and Northwestern, the majority through the Love/Avon Army of Women, and 380 completed study procedures. Median age 50 (36-60), mean BMI 28 (18.7-50.8), 52% were postmenopausal. Mean life-time Gail risk 14.6 (5.6-54.1), mean percent mammographic density 19.6 (2.5-72.8), and mean Masood score (N=354) 13.6 (7-18). QM-MSP analysis was completed on 229 samples. We did not observe differences in CMI among menopausal (P=0.4895) or menstrual categories (P=0.2333). There was no association between CMI and life-time Gail risk (P=0.706) or breast density (P=0.4116). We observed a significant correlation between CMI and Masood score (P=0.0167). Conclusions: CMI correlates with degree of cytologic atypia and is potentially a robust indicator of breast cancer risk since it does not vary with menstrual or menopausal status. Next, we will select genes that best reflect changes in the clinical parameters to create a gene methylation signature that will be validated in other studies and correlated with breast cancer risk.

The relationship of breast density, BMI, and menopausal status in mammography and MRI.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 36-36 ◽  
Author(s):  
Jennifer Chun ◽  
Ana Paula Refinetti ◽  
Ana Klautau Leite ◽  
Freya Ruth Schnabel ◽  
Tsivia Hochman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Density ◽  
Menopausal Status ◽  
Mammographic Breast Density ◽  
Strong Positive Correlation ◽  
Background Parenchymal Enhancement ◽  
Increased Risk ◽  
The Relationship

36 Background: Mammographic breast density (BD) is associated with a 4- to 6-fold increased risk for developing breast cancer. A previous study has shown that background parenchymal enhancement (BPE) as measured on MRI can be correlated with breast cancer risk. Being overweight or obese is also an established risk factor for breast cancer. The purpose of this study was to evaluate the relationship between BD, BPE, FGT (assessment of fibroglandular tissue with contiguous MR images), and BMI in pre- and post-menopausal women. Methods: The Breast Cancer Database at NYU Langone Medical Center was queried and a total of 187 women had completed both screening mammograms and MRIs. Variables of interest included BD, BPE, FGT, BMI, and menopausal status. BD was defined by ACR classifications 1-4. FGT was assessed on a similar scale 1-4. BPE was categorized as minimal, mild, moderate, or marked. BMI (kg/m2) was grouped as underweight (≤18), normal (19-24), overweight (25-29), and obese (≥30). Statistical analyses were performed using Spearman Correlation Coefficients and Cochran Mantel Haenszel tests. Results: The median age in our cohort was 51 years (range 22-87 years). The majority were Caucasian (71%) with early stage breast cancers (75%). There was no correlation between BD and BPE (r=0.132) and a weak correlation between BPE and FGT (r=0.312). However, there was a strong positive correlation between BD and FGT (r=0.733). After adjusting for menopausal status, these correlations remained the same. When we stratified by BMI, we found the strongest positive association between BD and FGT among women with BMI≥25 (r=0.715). Conclusions: In our cohort of newly diagnosed breast cancer patients, BD and BPE were not correlated, even after adjusting for menopausal status. This implies that BD and BPE may represent different characteristics of breast tissue and may have different implications. We found a strong correlation between FGT and BD. This association was strongest in women who were overweight and obese. FGT is a more objective and quantitative measurement of breast density and may be more useful in quantitative breast cancer risk assessment.Further studies are necessary to determine if BPE and FGT are independent risk factors for breast cancer.

Mammographic breast density, its changes, and breast cancer risk in premenopausal and postmenopausal women

Cancer ◽  
2020 ◽  
Vol 126 (21) ◽  
pp. 4687-4696
Author(s):  
Eun Young Kim ◽  
Yoosoo Chang ◽  
Jiin Ahn ◽  
Ji‐Sup Yun ◽  
Yong Lai Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Breast Density ◽  
Mammographic Breast Density

scholarly journals Review of: Are breast density and bone mineral density independent risk factors for breast cancer?

2005 ◽  
Vol 8 (11) ◽  
Author(s):  
J. L. Hopper
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Bone Mineral Density ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Correlation Coefficient ◽  
Breast Density ◽  
Mammographic Breast Density ◽  
Mineral Density ◽  
Increased Risk

Citation of original article:K. Kerlikowske, J. Shepherd, J. Creasman, J. A. Tice, E. Ziv, S. R. Cummings. Are breast density and bone mineral density independent risk factors for breast cancer. Journal of the National Cancer Institute 2005; 97(7): 368–74.Abstract of the original articleBackground: Mammographic breast density and bone mineral density (BMD) are markers of cumulative exposure to estrogen. Previous studies have suggested that women with high mammographic breast density or high BMD are at increased risk of breast cancer. We determined whether mammographic breast density and BMD of the hip and spine are correlated and independently associated with breast cancer risk. Methods: We conducted a cross-sectional study (N = 15 254) and a nested case-control study (of 208 women with breast cancer and 436 control subjects) among women aged 28 years or older who had a screening mammography examination and hip BMD measurement within 2 years. Breast density for 3105 of the women was classified using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) categories, and percentage mammographic breast density among the case patients and control subjects was quantified with a computer-based threshold method. Spearman rank partial correlation coefficient and Pearson's correlation coefficient were used to examine correlations between BI-RADS breast density and BMD and between percentage mammographic breast density and BMD, respectively, in women without breast cancer. Logistic regression was used to examine the association of breast cancer with percentage mammographic breast density and BMD. All statistical tests were two-sided. Results: Neither BI-RADS breast density nor percentage breast density was correlated with hip or spine BMD (correlation coefficient = −.02 and −.01 for BI-RADS, respectively, and −2.06 and .01 for percentage breast density, respectively). Neither hip BMD nor spine BMD had a statistically significant relationship with breast cancer risk. Women with breast density in the highest sextile had an approximately threefold increased risk of breast cancer compared with women in the lowest sextile (odds ratio: 2.7; 95% confidence interval: 1.4–5.4); adjusting for hip or spine BMD did not change the association between breast density and breast cancer risk. Conclusion: Breast density is strongly associated with increased risk of breast cancer, even after taking into account reproductive and hormonal risk factors, whereas BMD, although a possible marker of lifetime exposure to estrogen, is not. Thus, a component of breast density that is independent of estrogen-mediated effects may contribute to breast cancer risk.

Sign in / Sign up

Export Citation Format

Share Document