scholarly journals Use of systemic glucocorticoids and risk of breast cancer in a prospective cohort of postmenopausal women

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Manon Cairat ◽  
Marie Al Rahmoun ◽  
Marc J. Gunter ◽  
Pierre-Etienne Heudel ◽  
Gianluca Severi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Breast Cancer Incidence ◽  
Breast Cancers ◽  
Systemic Glucocorticoid ◽  
Systemic Glucocorticoids

Abstract Background Glucocorticoids could theoretically decrease breast cancer risk through their anti-inflammatory effects or increase risk through immunosuppression. However, epidemiological evidence is limited regarding the associations between glucocorticoid use and breast cancer risk. Methods We investigated the association between systemic glucocorticoid use and breast cancer incidence in the E3N cohort, which includes 98,995 women with information on various characteristics collected from repeated questionnaires complemented with drug reimbursement data available from 2004. Women with at least two reimbursements of systemic glucocorticoids in any previous 3-month period since January 1, 2004, were defined as exposed. We considered exposure as a time-varying parameter, and we used multivariable Cox regression models to estimate hazard ratios (HRs) of breast cancer. We performed a competing risk analysis using a cause-specific hazard approach to study the heterogeneity by tumour subtype/stage/grade. Results Among 62,512 postmenopausal women (median age at inclusion of 63 years old), 2864 developed breast cancer during a median follow-up of 9 years (between years 2004 and 2014). Compared with non-exposure, glucocorticoid exposure was not associated with overall breast cancer risk [HR = 0.94 (0.85–1.05)]; however, it was associated with a higher risk of in situ breast cancer and a lower risk of invasive breast cancer [HRinsitu = 1.34 (1.01–1.78); HRinvasive = 0.86 (0.76–0.97); Phomogeneity = 0.01]. Regarding the risk of invasive breast cancer, glucocorticoid exposure was inversely associated with oestrogen receptor (ER)-positive breast cancer [HRER+ = 0.82 (0.72–0.94); HRER− = 1.21 (0.88–1.66); Phomogeneity = 0.03]; it was also inversely associated with the risk of stage 1 or stage 2 tumours but positively associated with the risk of stage 3/4 breast cancers [HRstage1 = 0.87 (0.75–1.01); HRstage2 = 0.67 (0.52–0.86); HRstage3/4 = 1.49 (1.02–2.20); Phomogeneity = 0.01]. Conclusion This study suggests that the association between systemic glucocorticoid use and breast cancer risk may differ by tumour subtype and stage.

scholarly journals Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

2021 ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Endogenous Hormones ◽  
Uk Biobank ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

scholarly journals Considerations When Using Breast Cancer Risk Models for Women with Negative BRCA1/BRCA2 Mutation Results

2019 ◽  
Vol 112 (4) ◽  
pp. 418-422
Author(s):  
Robert J MacInnis ◽  
Yuyan Liao ◽  
Julia A Knight ◽  
Roger L Milne ◽  
Alice S Whittemore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Disease Incidence ◽  
Brca2 Mutation ◽  
Estimation Algorithm ◽  
Breast Cancers ◽  
Risk Models ◽  
Replication Studies

Abstract The performance of breast cancer risk models for women with a family history but negative BRCA1 and/or BRCA2 mutation test results is uncertain. We calculated the cumulative 10-year invasive breast cancer risk at cohort entry for 14 657 unaffected women (96.1% had an affected relative) not known to carry BRCA1 or BRCA2 mutations at baseline using three pedigree-based models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, BRCAPRO, and International Breast Cancer Intervention Study). During follow-up, 482 women were diagnosed with invasive breast cancer. Mutation testing was conducted independent of incident cancers. All models underpredicted risk by 26.3%–56.7% for women who tested negative but whose relatives had not been tested (n = 1363; 63 breast cancers). Although replication studies with larger sample sizes are needed, until these models are recalibrated for women who test negative and have no relatives tested, caution should be used when considering changing the breast cancer risk management intensity of such women based on risk estimates from these models.

The Women’s Health Initiative randomized trial of calcium plus vitamin D: Effects on breast cancer and arthralgias

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA6-LBA6 ◽  
Author(s):  
R. T. Chlebowski ◽  
K. C. Johnson ◽  
C. Kooperberg ◽  
A. Hubbell ◽  
D. Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Breast Cancer Incidence ◽  
Secondary Outcome ◽  
Baseline Serum ◽  
Abnormal Mammogram ◽  
Joint Symptoms

LBA6 Background: Calcium (Ca) and vitamin D (D) have been associated with reduced breast cancer and breast density in observational studies. Randomized trials have not evaluated Ca/D supplementation for breast cancer prevention. Methods: We randomized 36,282 postmenopausal women without prior breast cancer from 40 WHI centers to 1000 mg of elemental calcium as calcium carbonate and 400 IU of vitamin D3 (N = 18,176) daily or matching placebo (N = 18,106); 54% were also randomized one year previously to hormone therapy (HT) or placebo; conjugated equine estrogen (CEE) plus medroxyprogesterone acetate or CEE alone (the latter for those with prior hysterectomy). Ca/D effects on hip fracture and colorectal cancer have been reported (NEJM 2006). We report here pathologically confirmed invasive breast cancer as a secondary outcome of the Ca/D trial. Baseline serum 25(OH) D levels (in 1787 women) and serial joint symptoms (pain/stiffness and hand/feet swelling 0–3 scale, in a 6% sample) were also assessed. Results: Breast cancer incidence did not differ between Ca/D and placebo randomization groups (528 and 546 cases in Ca/D and placebo; hazard ratio 0.96; 95 percent confidence interval (CI), 0.85, 1.09). While SEER stage and abnormal mammogram frequency were similar between groups, breast cancers were smaller in the Ca/D group (1.54 cm (1.23), mean (SD) versus 1.71 (1.29), P = 0.05). Total vitamin D baseline intake was associated with lower breast cancer risk in the placebo group. Baseline vitamin D (nmol per liter) deficiency was common (≥30, sufficient (n = 266), 16 ≤ 30, insufficient (277), < 16, deficient (743)) but was not related to joint pain (seen in 72.2%, 74.0%, 74.6%, of sufficiency and deficiency groups, respectively). Joint symptoms were lower in women randomized to CEE alone (P < 0.01) but did not significantly differ by Ca/D group assignment and no significant interactions were seen between HT and Ca/D. Conclusion: Among healthy postmenopausal women, Ca/D supplementation did not reduce breast cancer risk but the cancers in those randomized to Ca/D were somewhat smaller. Exogenous estrogen use but not Ca/D supplementation influences arthralgias. [Table: see text]

Metformin and breast cancer risk: A meta-analysis and critical literature review.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 25-25
Author(s):  
Nananda Col ◽  
Leslie Ochs ◽  
Vicky Springmann ◽  
Aaron K Aragaki ◽  
Rowan T. Chlebowski
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Literature Review ◽  
Cancer Incidence ◽  
Invasive Breast Cancer ◽  
Meta Analysis ◽  
Breast Cancer Incidence ◽  
Cochrane Library ◽  
Study Quality

25 Background: Observational studies have suggested that metformin, commonly used for diabetes treatment that increases insulin sensitivity and improves glycemic control, decreases the incidence of several common cancers. However, findings regarding metformin and breast cancer incidence have been mixed. To explore this issue, a systematic literature review and meta-analysis were performed with a focus on potential biases. Methods: We conducted a comprehensive literature search for all pertinent studies addressing metformin use and breast cancer risk by searching Pub Med, Cochrane Library, Scopus (which includes Embase, ISI Web of Science) using the Mesh terms: "metformin" or "biguanides" or "diabetes mellitus, type 2/therapy" and "cancer" or "neoplasms". When multiple hazard ratios (HR) or odds ratio (OR) were reported, the most adjusted estimate was used in the base-case analysis. We pooled the adjusted HR using and performed sensitivity analyses on duration of metformin use (> or < 3 years use), study quality (assessed using the GRADE system), and initial observation year of the cohort (before vs after 1997). Results: From a total of 421 citations, 13 full-text articles were considered, and 7 independent studies were included. All were observational (4 cohort and 3 case control). Our combined OR for metformin association with invasive breast cancer of all 7 studies was 0.83 (95% CI, 0.71-0.97). Funnel plot analyses did not suggest publication bias. Stronger associations were found when analyses were limited to studies estimating the impact of longer metformin duration (OR = 0.75. 95% CI, 0.62-0.91) or among studies that began observing their cohort before 1997 (OR=0.68. 95% CI, 0.55-0.84). Stratification according to study quality did not affect the combined OR but higher quality studies had smaller CI and achieved statistical significance. Interpretation is limited by the observational nature of reports and different comparison groups. Conclusions: Our analyses support a protective effect of metformin on invasive breast cancer incidence among postmenopausal women with diabetes. Clinical trials are needed to determine whether metformin reduces breast cancer risk.

scholarly journals 673Is weight more informative than body mass index for breast cancer risk

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Zhoufeng Ye ◽  
Gillian Dite ◽  
John Hopper
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Body Mass ◽  
Cox Regression ◽  
Menopausal Status ◽  
Familial Risk ◽  
Study Cohort ◽  
Breast Cancers

Abstract Background Our previous work on body mass index (BMI) and breast cancer risk found that the association depended on menopausal status but not on familial risk (Hopper, JL., et al, 2018). We now consider whether weight is a more informative risk factor for breast cancer than BMI. Methods We used data from the Prospective Family Study Cohort, a consortium of international prospective cohorts that are enriched for familial risk of breast cancer and include 16,035 unaffected women from 6701 families. Participants were followed for up to 20 years (mean 10.5 years) and there were 896 incident breast cancers with a mean age at diagnosis of 55.7 years. Cox regression was used to model risk associations as a function of age, menopausal status and underlying familial risk. We calculated robust confidence intervals by clustering by family. Model comparisons were made using the Bayesian Information Criterion (BIC). Results In repeating the best-fitting model from our original analyses, but using weight instead of BMI, we found that the log likelihood for the model using weight was 1.92 units greater than for the model using BMI (difference in BIC = 3.84). Therefore, the data are almost 50 times more likely under the model using weight. Conclusions The study found positive evidence that weight gives more information on risk than does BMI. Key messages Analysing breast cancer risk in terms of weight, rather than only BMI, might give greater insight and results that are easier to convey to the public.

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 Effect of Raloxifene on the Incidence of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis Categorized by Breast Cancer Risk

2006 ◽  
Vol 12 (17) ◽  
pp. 5242-5247 ◽  
Author(s):  
Marc E. Lippman ◽  
Steven R. Cummings ◽  
Damon P. Disch ◽  
John L. Mershon ◽  
Sherie A. Dowsett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Invasive Breast Cancer

Breast Risk Reduction

2007 ◽  
Vol 5 (8) ◽  
pp. 774
Author(s):  
_ _
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Risk Reduction ◽  
Breast Cancer Incidence ◽  
Female Gender ◽  
Breast Cancers ◽  
Increased Risk ◽  
Reduce Breast Cancer Risk

Breast cancer is the most commonly diagnosed cancer in American women, with an estimated 214,640 cases and 41,430 deaths occurring in 2006. Estimating breast cancer risk for individual women is difficult, and most breast cancers are not attributable to risk factors other than female gender and increased age. Developing effective strategies for reducing breast cancer incidence is also difficult because few existing risk factors are modifiable and some potentially modifiable risk factors have social implications. Nevertheless, effective breast cancer risk reduction agents and strategies, such as tamoxifen, raloxifene, and risk reduction surgery, have been identified. These guidelines were developed to help women at increased risk for breast cancer and their physicians apply individualized strategies to reduce breast cancer risk. For the most recent version of the guidelines, please visit NCCN.org

Urinary Estrogen Metabolites and Breast Cancer: A Combined Analysis of Individual Level Data

2013 ◽  
Vol 28 (1) ◽  
pp. 3-16 ◽  
Author(s):  
Cher M. Dallal ◽  
Roslyn A. Stone ◽  
Jane A. Cauley ◽  
Roberta B. Ness ◽  
Victor G. Vogel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Invasive Breast Cancer ◽  
Multinomial Logistic Regression ◽  
Primary Data ◽  
Breast Carcinogenesis ◽  
Estrogen Metabolites ◽  
Combined Analysis

Background Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and their ratio (2:16α-OHE1) in relation to breast cancer risk. Methods Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status. Results Higher premenopausal 2:16α-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16α-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). Conclusions Premenopausal urinary 2:16α-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16α-OHE1 overall, although obesity may modify associations with 2-OHE1.

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