scholarly journals Adiposity and estrogen receptor‐positive, postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol

2019 ◽  
Vol 146 (6) ◽  
pp. 1541-1552 ◽  
Author(s):  
S. Ghazaleh Dashti ◽  
Julie A. Simpson ◽  
Amalia Karahalios ◽  
Vivian Viallon ◽  
Margarita Moreno‐Betancur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Breast Cancer ◽  
Fasting Insulin ◽  
Mediating Effects ◽  
Risk Quantification ◽  
Estrogen Receptor Positive ◽  
Free Estradiol

scholarly journals Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis

2018 ◽  
Vol 48 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Xiang Shu ◽  
Lang Wu ◽  
Nikhil K Khankari ◽  
Xiao-Ou Shu ◽  
Thomas J Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mendelian Randomization ◽  
Menopausal Status ◽  
Inverse Association ◽  
Fasting Insulin

Abstract Background In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10–4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10–4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10–19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10–6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.

scholarly journals Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk

2018 ◽  
Vol 58 (3) ◽  
pp. 1033-1045 ◽  
Author(s):  
Janneke G. F. Hogervorst ◽  
Piet A. van den Brandt ◽  
Roger W. L. Godschalk ◽  
Frederik-Jan van Schooten ◽  
Leo J. Schouten
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Estrogen Receptor Positive ◽  
Dietary Acrylamide ◽  
Positive Breast Cancer

Predicting risk of estrogen receptor positive breast cancers in postmenopausal women

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1507-1507
Author(s):  
R. T. Chlebowski ◽  
G. L. Anderson ◽  
D. S. Lane ◽  
A. Aragaki ◽  
T. Rohan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Estrogen Receptor ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Breast Biopsy ◽  
Breast Cancers ◽  
Estrogen Receptor Positive

1507 Background: Chemoprevention strategies for estrogen receptor positive (ER+) breast cancers are emerging, especially for postmenopausal women, but require methods of targeting appropriate populations. Our objective was to improve the Breast Cancer Risk Assessment Tool [Gail Model (GM)] for estimating ER+ breast cancer risk. Methods: A prospective cohort involving 161,809 postmenopausal women aged 50–79 years, (93,676 in the observational study (OS) and 68,132 in clinical trials (CT)) at Women’s Health Initiative (WHI) Clinical Centers had comprehensive assessment of lifestyle, medication use and breast cancer risk factors. Breast cancer risk from the GM and other models incorporating additional or fewer risk factors and five year incidence of ER + and ER negative (ER-) invasive breast cancers were determined. Main outcome measures were concordance statistics for models predicting breast cancer risk. Results: Of 148,266 women meeting eligibility criteria, (no prior breast cancer and/or mastectomy), 3,236 developed breast cancer. Chronological age and age at menopause, both GM components, were significantly associated with only ER+ but not ER- breast cancer risk (p<0.05 for heterogeneity test). The GM predicted population-based ER+ cancer risk with reasonable accuracy (concordance statistic 0.60, 95% confidence interval (CI) 0.58 to 0.62) but for ER- cancers, the results were equivalent to chance allocation (concordance statistic 0.49, 95% CI 0.45 to 0.54). For ER+ cancers, no additional risk factors improved the GM prediction. However, a simpler model, developed in the OS and tested in the CT population, including only age, family history, and benign breast biopsy was comparable to GM in ER+ breast cancer prediction (concordance statistics 0.58, 95% CI 0.56 to 0.60). Using this model, all women ≥ 55 years old (or ≥ 60 year old if African American) with either a prior breast biopsy or first degree breast cancer family history had five year breast cancer risk of ≥ 1.8%. Conclusions: In postmenopausal women with comprehensive mammography use, the GM identifies populations at increased risk for ER+ breast cancer but not for ER- cancer. A model with fewer variables provides a simpler alternative for identifying populations appropriate for breast cancer chemoprevention interventions. No significant financial relationships to disclose.

scholarly journals Estrogen receptor α polymorphisms and postmenopausal breast cancer risk

2007 ◽  
Vol 107 (3) ◽  
pp. 415-419 ◽  
Author(s):  
A. M. González-Zuloeta Ladd ◽  
A. Arias Vásquez ◽  
F. Rivadeneira ◽  
C. Siemes ◽  
A. Hofman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Breast Cancer ◽  
Estrogen Receptor Α ◽  
Postmenopausal Breast Cancer Risk

scholarly journals Migraine History and Breast Cancer Risk Among Postmenopausal Women

2010 ◽  
Vol 28 (6) ◽  
pp. 1005-1010 ◽  
Author(s):  
Christopher I. Li ◽  
Robert W. Mathes ◽  
Elizabeth C. Bluhm ◽  
Bette Caan ◽  
Mary F. Cavanagh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Lower Risk ◽  
No Reduction ◽  
Postmenopausal Breast Cancer ◽  
Estrogen Receptor Positive ◽  
History Of ◽  
Inflammatory Drugs ◽  
The Relationship

Purpose Both migraine and breast cancer are hormonally mediated. Two recent reports indicate that women with a migraine history may have a lower risk of postmenopausal breast cancer than those who never suffered migraines. This finding requires confirmation; in particular, an assessment of the influence of use of nonsteroidal anti-inflammatory drugs (NSAID) is needed, because many studies indicate that NSAID use also may confer a reduction in breast cancer risk. Methods We assessed the relationship between self-reported history of migraine and incidence of postmenopausal breast cancer in 91,116 women enrolled on the Women's Health Initiative Observational Study prospective cohort from 1993 to 1998 at ages 50 to 79 years. Through September 15, 2005, there were 4,006 eligible patients with breast cancer diagnosed. Results Women with a history of migraine had a lower risk of breast cancer (hazard ratio [HR], 0.89; 95% CI, 0.80 to 98) than women without a migraine history. This risk did not vary by recent NSAID use. The lower risk was somewhat more pronounced for invasive estrogen-receptor–positive and progesterone-receptor–positive tumors (HR, 0.83; 95% CI, 0.71 to 0.97), as no reduction in risk was observed for invasive ER-negative/PR-negative tumors (HR, 1.16; 95% CI, 0.86 to 1.57), and this difference in risk estimates was borderline statistically significant (P = .06). Conclusion This study supports the hypothesis that a history of migraine is associated with a lower risk of breast cancer and that this relationship is independent of recent NSAID use.

scholarly journals Lifetime body size and estrogen-receptor-positive breast cancer risk in the California Teachers Study cohort

2016 ◽  
Vol 18 (1) ◽  
Author(s):  
Pamela L. Horn-Ross ◽  
Alison J. Canchola ◽  
Leslie Bernstein ◽  
Susan L. Neuhausen ◽  
David O. Nelson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Body Size ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Study Cohort ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

scholarly journals Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal women

2013 ◽  
Vol 21 (2) ◽  
pp. 263-273 ◽  
Author(s):  
Vanessa W Lim ◽  
Jun Li ◽  
Yinhan Gong ◽  
Aizhen Jin ◽  
Jian-Min Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Breast Cancer ◽  
Positive Association ◽  
Serum Levels ◽  
Population Based ◽  
Health Study ◽  
Baseline Serum

The estrogen levels of Asian women are different from those of Western women, and this could affect estrogen receptor (ER) bioactivity and breast cancer risk. We conducted a case–control study in 169 postmenopausal breast cancer cases and 426 matched controls nested within a population-based prospective cohort study, the Singapore Chinese Health Study, to evaluate the serum levels of estrogens and their receptor (ERα and ERβ)-mediated estrogenic activities in relation to breast cancer risk. Breast cancer cases had higher levels of estrogens and ER-mediated bioactivities in baseline serum than the controls. Compared with those in the lowest quartile, women in the highest quartile for estrone (E1) or ERα-mediated bioactivity had increased breast cancer risk. After additional adjustment for ERβ bioactivity, free estradiol, and E1levels, serum ERα-mediated bioactivity remained associated with increased breast cancer risk. Compared with those in the lowest quartile, women in the highest quartile for ERα-mediated bioactivity had an odds ratio of 2.39 (95% CI=1.17–4.88;Pfor trend=0.016). Conversely, the positive association between E1and cancer risk became null after adjustment for ERα-mediated bioactivity, suggesting that the effect of E1could be mediated through ERα. Factor(s) contributing to increased ERα-mediated estrogenic bioactivity in serum and its role as a predictor for breast cancer risk need to be validated in future studies.

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