scholarly journals Biomarkers of mammographic density in premenopausal women

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Mathilde His ◽  
Martin Lajous ◽  
Liliana Gómez-Flores-Ramos ◽  
Adriana Monge ◽  
Laure Dossus ◽  
...  

Abstract Background While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density. Methods A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers’ Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors. Results Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components. Conclusions We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Olivia Moran ◽  
Andrea Eisen ◽  
Rochelle Demsky ◽  
Kristina Blackmore ◽  
Julia A. Knight ◽  
...  

Abstract Background Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. Methods We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. Results Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. Conclusions In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.


2020 ◽  
Vol 61 (12) ◽  
pp. 1600-1607
Author(s):  
Roxanna Hellgren ◽  
Ariel Saracco ◽  
Fredrik Strand ◽  
Mikael Eriksson ◽  
Ann Sundbom ◽  
...  

Background Background parenchymal enhancement (BPE) of normal tissue at breast magnetic resonance imaging is suggested to be an independent risk factor for breast cancer. Its association with established risk factors for breast cancer is not fully investigated. Purpose To study the association between BPE and risk factors for breast cancer in a healthy, non-high-risk screening population. Material and Methods We measured BPE and mammographic density and used data from self-reported questionnaires in 214 healthy women aged 43–74 years. We estimated odds ratios for the univariable association between BPE and risk factors. We then fitted an adjusted model using logistic regression to evaluate associations between BPE (high vs. low) and risk factors, including mammographic breast density. Results The majority of women had low BPE (84%). In a multivariable model, we found statistically significant associations between BPE and age ( P = 0.002) and BMI ( P = 0.03). We did find a significant association between systemic progesterone medication and BPE, but due to small numbers, the results should be interpreted with caution. The adjusted odds ratio for high BPE was 3.1 among women with density D (compared to B) and 2.1 for density C (compared to B). However, the association between high BPE and density was not statistically significant. We did not find statistically significant associations with any other risk factors. Conclusion Our study confirmed the known association of BPE with age and BMI. Although our results show a higher likelihood for high BPE with increasing levels of mammographic density, the association was not statistically significant.


Author(s):  
Juliane Wunder ◽  
Daniela Pemp ◽  
Alexander Cecil ◽  
Maryam Mahdiani ◽  
René Hauptstein ◽  
...  

AbstractBreast cancer etiology is associated with both proliferation and DNA damage induced by estrogens. Breast cancer risk factors (BCRF) such as body mass index (BMI), smoking, and intake of estrogen-active drugs were recently shown to influence intratissue estrogen levels. Thus, the aim of the present study was to investigate the influence of BCRF on estrogen-induced proliferation and DNA damage in 41 well-characterized breast glandular tissues derived from women without breast cancer. Influence of intramammary estrogen levels and BCRF on estrogen receptor (ESR) activation, ESR-related proliferation (indicated by levels of marker transcripts), oxidative stress (indicated by levels of GCLC transcript and oxidative derivatives of cholesterol), and levels of transcripts encoding enzymes involved in estrogen biotransformation was identified by multiple linear regression models. Metabolic fluxes to adducts of estrogens with DNA (E-DNA) were assessed by a metabolic network model (MNM) which was validated by comparison of calculated fluxes with data on methoxylated and glucuronidated estrogens determined by GC– and UHPLC–MS/MS. Intratissue estrogen levels significantly influenced ESR activation and fluxes to E-DNA within the MNM. Likewise, all BCRF directly and/or indirectly influenced ESR activation, proliferation, and key flux constraints influencing E-DNA (i.e., levels of estrogens, CYP1B1, SULT1A1, SULT1A2, and GSTP1). However, no unambiguous total effect of BCRF on proliferation became apparent. Furthermore, BMI was the only BCRF to indeed influence fluxes to E-DNA (via congruent adverse influence on levels of estrogens, CYP1B1 and SULT1A2).


2021 ◽  
Author(s):  
Marco Fornili ◽  
Vittorio Perduca ◽  
Agnès Fournier ◽  
Allan Jérolon ◽  
Marie Christine Boutron-Ruault ◽  
...  

Abstract BACKGROUND Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study. METHODS We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association of mammographic density with MHT was evaluated by linear regression models. Mediation modelling techniques were applied to estimate under the hypothesis of a causal model the proportion of the effect of MHT on BC risk mediated by percent mammographic density for BC overall and by hormonal receptor status. RESULTS Among MHT users, only 4.2% used exclusively estrogens compared with 68.3% who used exclusively estrogens plus progestogens. Mammographic density was higher in current users (mean percent mammographic density for a 60 year old woman 33%; 95% CI: 31% to 35%) than in past (29%; 27% to 31%) and never users (24%; 22% to 26%). Mammographic density increased with the duration of MHT within one year of therapy and reached a steady state thereafter. After MHT discontinuation, mammographic density decreased with time since last use and reached values similar to those of never users after 8 years. The OR of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by percent mammographic density was 34% for any BC and became 48% when the correlation between BMI and percent mammographic density was accounted for. These effects were limited to hormone receptor positive BC. CONCLUSIONS Our results suggest that under a causal model nearly half of the effect of MHT on hormone receptor positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.


2020 ◽  
Author(s):  
Marco Fornili ◽  
Vittorio Perduca ◽  
Agnès Fournier ◽  
Allan Jérolon ◽  
Marie Christine Boutron-Ruault ◽  
...  

Abstract BACKGROUND: Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study is to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study.METHODS: The data analyzed refer to a case-control study nested into the French cohort E3N and include 453 cases and 453 matched controls. A quantitative measure of mammographic density, a detailed history of MHT use during follow-up and information on potential confounders were available for all women. The association of mammographic density with MHT duration and time since last use was evaluated by linear regression models. Mediation modelling techniques were applied to estimate under the hypothesis of a causal model the proportion of the effect of MHT on BC risk mediated by percent mammographic density for BC overall and by ER/PR status.RESULTS: Mammographic density was higher in current (mean percent mammographic density 33%; 95% CI: 31–35%) than in former (29%; 95% CI 27% to 31) and never users (24%; 95% CI, 22–26%). Mammographic density increased with the duration of MHT within one year of therapy and reached a steady state thereafter. After discontinuation of the therapy, mammographic density decreased with time since last use and reached values similar to those of never users after 8 years. The OR of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by percent mammographic density was 34% on the log scale for any BC and became 48% when the correlation between BMI and percent mammographic density was accounted for. These results are limited to hormone receptor positive BCs.CONCLUSIONS: Our results suggest that under a causal model the effect of MHT on BC risk was partially mediated by MD that appeared to be modified by MHT for up to 8 years after MHT termination.


2005 ◽  
Vol 23 (4) ◽  
pp. 766-773 ◽  
Author(s):  
Christine M. Duffy ◽  
Susan M. Allen ◽  
Melissa A. Clark

Purpose Young women who undergo chemotherapy for breast cancer face serious consequences to their reproductive health. Research in this area has previously focused on men, or on childhood cancer survivors. We sought to explore self-report of reproductive health counseling in young women undergoing chemotherapy for breast cancer. Patients and Methods A total of 166 premenopausal women aged ≤ 50 years were recruited from oncology offices in academic and private practices in four northeastern states, as part of a randomized controlled clinical trial aimed at stress reduction. Women were asked a variety of questions regarding diagnosis and treatment, including whether they received any counseling regarding early menopause and fertility issues. Results Sixty-eight percent and 34% of women reported recalling a discussion with a physician regarding early menopause or fertility, respectively. In multivariate analysis, hormonal therapy and early stage of disease were associated with significantly increased odds of recall of a discussion regarding menopause. Difficulty communicating with medical team was associated with increased odds of recalling a discussion regarding fertility, whereas older age and anxiety in medical situations were associated with decreased odds. Conclusion Many women fail to recall discussions regarding the reproductive health impact of chemotherapy. Demographic, psychological, and disease-related variables are related to recalling such discussions. Counseling about premature menopause and fertility changes is an overlooked aspect of preparation for adjuvant chemotherapy in young premenopausal women with breast cancer. Future research should explore this issue further.


1999 ◽  
Vol 35 (1) ◽  
pp. 16-26 ◽  
Author(s):  
Savitri K. Kamath ◽  
Genoveva Murillo ◽  
Robert T. Chatterton ◽  
Erum A. Hussain ◽  
Daxa Amin ◽  
...  

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