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

Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key

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.

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K Reeves ◽  
Timothy J Key

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. We investigated the associations between serum concentrations of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1) and oestradiol (pre-menopausal women only) and the risk of invasive breast cancer using data from UK Biobank. Methods We included 30,565 pre-menopausal and 133,294 post-menopausal women in this analysis. Hormone concentrations were measured in serum collected between 2006 and 2010, and incident cancer cases were identified through linkage to cancer and death registries. Multivariable Cox proportional hazards models were used, and hazard ratios (HRs) were corrected for regression dilution bias using repeat measures collected in about 5,000 women four years after recruitment (except for oestradiol). Results During a median follow-up of 7.1 years, 527 pre-menopausal and 2,997 post-menopausal women were diagnosed with invasive breast cancer. 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 premenopausal women (pheterogeneity=0.03), and with IGF-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 (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 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. Key messages Breast cancer risk was positively associated with testosterone and inversely associated with SHBG in post-menopausal women, and positively associated with IGF-1 in both pre- and post-menopausal women.


2019 ◽  
Vol 109 (5) ◽  
pp. 1393-1401 ◽  
Author(s):  
Joshua Petimar ◽  
Yong-Moon Mark Park ◽  
Stephanie A Smith-Warner ◽  
Teresa T Fung ◽  
Dale P Sandler

ABSTRACT Background Many epidemiologic studies have analyzed the relations of individual foods and nutrients and breast cancer risk with inconsistent results. Few studies have examined recommendation-based dietary indices and breast cancer risk. Objective The aim of this study was to determine associations between recommendation-based dietary index scores and incident invasive breast cancer. Methods The Sister Study is a prospective cohort of 50,884 US women (baseline: 2003–2009) who had a sister with breast cancer but no prior breast cancer themselves. We created scores for the Dietary Approaches to Stop Hypertension (DASH) diet, Alternative Mediterranean Diet (AMED), and Alternative Healthy Eating Index–2010 (AHEI-2010) from dietary intakes estimated by a baseline-validated Block food-frequency questionnaire (FFQ). We used Cox regression to estimate multivariable-adjusted HRs and 95% CIs for total invasive breast cancer risk and by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status. Results We documented 1,700 invasive breast cancer cases through 2015 (mean follow-up, 7.6 y). Individuals in the highest quartile of DASH scores had a lower risk of invasive breast cancer compared with those in the lowest quartile (HR: 0.78; 95% CI: 0.67, 0.90; P-trend = 0.001), with stronger associations for ER– (HR: 0.61; 95% CI: 0.40, 0.94; P-trend = 0.006) as well as ER–/PR– and ER–/PR–/HER2– subtypes. AHEI-2010 (HR for highest compared with lowest quartile: 0.90; 95% CI: 0.78, 1.03; P-trend = 0.15) and AMED (HR for highest compared with lowest quartile: 0.90; 95% CI: 0.77, 1.06; P-trend = 0.07) were weakly and nonsignificantly associated with breast cancer risk, but after excluding alcohol, AHEI-2010 was inversely associated with risk of ER–/PR– (HR: 0.64; 95% CI: 0.42, 0.98; P-trend = 0.04) and ER–/PR–/HER2– subtypes. We did not observe any significant interactions by menopausal status or other participant characteristics. Conclusions DASH scores were inversely associated with breast cancer risk; DASH and AHEI-2010 scores excluding alcohol were particularly inversely associated with risk of ER–/PR– and ER–/PR–/HER2– breast cancers. This trial was registered at clinicaltrials.gov as NCT00047970.


Author(s):  
Cecilia Magnusson ◽  
John Baron ◽  
Ingemar Persson ◽  
Alicja Wolk ◽  
Reinhold Bergström ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 731
Author(s):  
Rodrigo Sánchez-Bayona ◽  
Alfredo Gea ◽  
Itziar Gardeazabal ◽  
Andrea Romanos-Nanclares ◽  
Miguel Ángel Martínez-González ◽  
...  

Alcohol intake is associated with the risk of breast cancer. Different patterns of alcohol-drinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03–2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11–3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.


2020 ◽  
Vol 122 (5) ◽  
pp. 726-732 ◽  
Author(s):  
Wenji Guo ◽  
Georgina K. Fensom ◽  
Gillian K. Reeves ◽  
Timothy J. Key

Abstract Background Previous studies suggest a protective role of physical activity in breast cancer risk, largely based on self-reported activity. We aimed to clarify this association by examining breast cancer risk in relation to self-reported physical activity, informed by accelerometer-based measures in a large subset of participants. Methods We analysed data from 47,456 premenopausal and 126,704 postmenopausal women in UK Biobank followed from 2006 to 2014. Physical activity was self-reported at baseline, and at resurvey in a subsample of 6443 participants. Accelerometer data, measured from 2013 to 2015, were available in 20,785 women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using multivariable-adjusted Cox regression. Results A total of 3189 cases were diagnosed during follow-up (mean = 5.7 years). Women in the top compared with the bottom quartile of self-reported physical activity had a reduced risk of both premenopausal (RR 0.75; 95% CI 0.60–0.93) and postmenopausal breast cancer (RR 0.87; 95% CI 0.78–0.98), after adjusting for adiposity. In analyses utilising physical activity values assigned from accelerometer measurements, an increase of 5 milli-gravity was associated with a 21% (RR 0.79; 95% CI 0.66–0.95) reduction in premenopausal and a 16% (RR 0.84; 95% CI 0.73–0.96) reduction in postmenopausal breast cancer risk. Conclusions Greater physical activity is associated with a reduction in breast cancer risk, which appears to be independent of any association it may have on risk through its effects on adiposity.


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Zhoufeng Ye ◽  
Gillian Dite ◽  
John Hopper

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.


2020 ◽  
Vol 112 (9) ◽  
pp. 893-901 ◽  
Author(s):  
Rhonda S Arthur ◽  
Tao Wang ◽  
Xiaonan Xue ◽  
Victor Kamensky ◽  
Thomas E Rohan

Abstract Background Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal. Methods Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146 326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci. Results Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low = 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29%, and 32% reductions in risk of invasive breast cancer in the low, intermediate, and high PRS groups, respectively (HRhigh vs low = 0.70, 95% CI = 0.56 to 0.88; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women. Conclusion Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.


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