Birthweight and body size throughout life in relation to sex hormones and prolactin concentrations in premenopausal women.

The association of birthweight and body size throughout life with premenopausal breast cancer risk may be due, in part, to relationships with sex hormones. Therefore, we assessed whether birthweight, body shape at ages 5 and 10, body mass index (BMI) at age 18 and adulthood, adult waist circumference and waist-to-hip ratio (WHR), and attained height were associated with the plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone-binding globulin (SHBG) in 592 premenopausal women, ages 33 to 52 years old, from the Nurses' Health Study II. About 85% of women provided blood samples during follicular and luteal menstrual phases; other women had a single untimed sample. We observed few associations between sex hormone levels and birthweight or body shape in childhood. However, adult BMI was inversely associated with SHBG (P trend < 0.001) and positively associated with free testosterone (P trend < 0.001) concentrations. Adult BMI was not associated with follicular or luteal free estradiol levels (P trend >or= 0.15) because it was inversely associated with total estradiol levels (P trend < 0.001 for follicular and luteal estradiol levels). Testosterone, androstenedione, and progesterone were inversely associated with BMI. Comparing women with a BMI of >or=30 versus <20 kg/m2, levels were higher by 53% for free testosterone and lower by 51% for SHBG, 39% for follicular estradiol, 20% for luteal estradiol, 14% for androstenedione, 13% for testosterone, and 20% for progesterone. We observed no clear associations between BMI at age 18, waist circumference, WHR, or height, and sex hormone concentrations. Our results suggest that effects on premenopausal sex hormone levels may be one mechanism through which adult adiposity, but not birthweight or childhood body size, affects premenopausal breast cancer risk.     

Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition

Steroid hormones are associated with the risk of postmenopausal breast cancer and evidence suggests that increased concentrations of oestrogens from peripheral aromatisation in adipose tissue partly explains the association between body mass index (BMI) and risk of postmenopausal breast cancer. This study examined the associations between circulating concentrations of steroid hormones and anthropometric measurements in a sample of naturally postmenopausal women from the Melbourne Collaborative Cohort Study, not using hormone replacement therapy. We measured plasma concentration of total oestradiol, oestrone sulphate, dehydroepiandrosterone sulphate, androstenedione, testosterone and sex hormone binding globulin (SHBG) and calculated concentration of free oestradiol. Body measurements included height, weight, BMI, waist circumference, fat mass and fat-free mass, the last two estimated by bioelectrical impedance analysis. BMI was positively associated with both oestrogens and androgens and negatively with SHBG. Fat mass was the principal measure responsible for the association observed between body size and total oestradiol. The associations between oestrone sulphate and androgens and body size were mainly with waist circumference. The associations between oestrogens and body size were close to null for the first 6 years since menopause and became positive thereafter. Our results are compatible with the hypothesis that after the menopause excess fat mass increases oestrogen concentrations through the peripheral aromatisation of androgens in adipose tissue. This effect requires around 6 years to be detectable by way of circulating steroid hormone levels.     

C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated.Results: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women.Conclusions: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.     

Body size and composition,physical activity and sedentary time in relation to endogenous hormones in premenopausal and postmenopausal women: Findings from the UK Biobank

Anthropometric and lifestyle factors may influence cancer risks through hormonal changes. We investigated cross-sectional associations between body size and composition, physical activity and sedentary time and serum concentrations of oestradiol (premenopausal women only), testosterone, sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I) in 20 758 premenopausal and 71 101 postmenopausal women in UK Biobank. In premenopausal women, higher BMI (body mass index) was associated with a lower concentration of total oestradiol (15% difference in the highest vs lowest BMI group) and a higher concentration of calculated free oestradiol (22%). In both premenopausal and postmenopausal women, higher BMI was associated with higher concentrations of total and calculated free testosterone (premenopausal 29% and 113%, postmenopausal 39% and 126%, respectively) and lower concentrations of SHBG and IGF-I (premenopausal 51% and 14%, postmenopausal 51% and 12%, respectively). Similar associations were observed with waist to height ratio, waist to hip ratio and body or trunk fat mass. Self-reported physical activity was associated with somewhat lower concentrations of total and calculated free testosterone (premenopausal 10% difference [free testosterone], postmenopausal 5% and 11% difference respectively in the most vs least active group) and a higher concentration of SHBG (premenopausal 11%, postmenopausal 10%), and the opposite was true for self-reported sedentary time. The associations were slightly stronger with accelerometer-measured physical activity, but were attenuated after adjustment for BMI. Overall, our study confirms strong associations of hormones and SHBG with anthropometric factors. The associations with physical activity and sedentary time were at most modest.     

Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort

In a large case-control study on breast cancer risk and serum hormone concentrations, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids. Height, weight, waist and hip circumferences, and serum measurements of testosterone [T], androstenedione [Delta4], dehydroepiandrosterone sulphate [DHEAS], estradiol [E2], estrone [E1] and sex-hormone binding globulin [SHBG] were available for 613 breast cancer cases, and 1,139 matched controls, who were all menopausal at the time of blood donation. Free T [fT] and free E2 [fE2] were calculated using mass action equations. Breast cancer risk was related to body mass index (BMI) (RR = 1.11 [0.99-1.25], per 5 kg/m2 increase in BMI), and waist (RR = 1.12 [1.02-1.24], per 10 cm increase) and hip circumferences (RR = 1.14 [1.02-1.27], per 10 cm increase). The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens, especially for fE2 (from 1.11 [0.99-1.25] to 0.99 [0.87-1.12], from 1.12 [1.02-1.24] to 1.02 [0.92-1.14] and from 1.14 [1.02-1.27] to 1.05 [0.93-1.18] for BMI, waist and hip circumferences, respectively). A modest attenuation in excess risk was observed after adjustment for fT, but the remaining androgens had little effect on the association of body adiposity with breast cancer. Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens, and by a decrease in levels of SHBG.     

Usefulness of body mass index as a sufficient adiposity measurement for sex hormone concentration associations in postmenopausal women.

BACKGROUND: Both obesity and sex hormones are known risk factors for postmenopausal breast cancer. Although adiposity and sex hormones have been studied in the past, previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions. In this study, we investigated the usefulness of body mass index (BMI) as a sufficient adiposity measurement to assess associations with sex hormone levels. METHODS: This study was conducted as a cross-sectional analysis within the control segment (0 g alcohol group) of a randomized, crossover design, in which 51 postmenopausal women consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks each as part of a controlled diet. Dual-energy X-ray absorptiometry scans were administered to the women during the control (0 g alcohol) segment, and a blood sample was drawn at the end of that diet period for hormone analysis. RESULTS: In multivariate analysis (adjusted for age, race, family history of breast cancer, parity, and menarche <12 years), women who were overweight or obese had significantly higher serum concentrations of estradiol, bioavailable estradiol, estrone, and estrone sulfate and lower sex hormone-binding globulin than normal weight women (all P < 0.05). In models adjusted for BMI and the covariates above, none of the dual-energy X-ray absorptiometry adiposity measures added further information (all P > 0.10) for these five analytes beyond that of BMI alone. CONCLUSIONS: In this population of postmenopausal women, under carefully controlled dietary conditions, we confirmed previous findings that higher levels of adiposity were associated with higher concentrations of estrogens and lower sex hormone-binding globulin, and we found that the use of the epidemiology-friendly BMI seems sufficient to assess associations with these hormone levels.     

Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies

BACKGROUND: Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk. We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women. METHODS: We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not. None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels. The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case-control sets matched within each study. Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate. RESULTS: The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21 (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to 2.71; P(trend)<.001); the RRs for women with increasing quintiles of free estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24 (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The magnitudes of risk associated with the other estrogens and with the androgens were similar. SHBG was associated with a decrease in breast cancer risk (P(trend) =.041). The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis. CONCLUSION: Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women.     

血清性激素水平和体重指数与绝经后女性乳腺癌发病的相关性研究

目的 探讨绝经后女性乳腺癌的发病与血清性激素水平和体重指数的关系。方法 选择2013年3月—12月在哈尔滨医科大学附属肿瘤医院乳腺外科接受手术治疗的初诊绝经后乳腺癌118例作为病例组以及60例绝经后乳腺良性病变者作为对照组,并收集所有受试对象的身高、体重等基本资料。应用酶联免疫吸附实验(ELISA)方法检测受试对象的血清雌二醇(Estradiol,E2)、雌酮(Estrone,E1)、睾酮(Testesterone,TSTO)以及雄烯二酮(Androstenedione,AED)水平,并对结果进行分析。结果 病例组血清E2、E1、AED水平显著高于对照组(P＜0.05),病例组的血清TSTO平均水平稍高于对照组,但差异无统计学意义(P＞0.05);病例组体重指数(BMI)与对照组无明显差异(P＞0.05);病例组血清E1以及总研究对象的血清E1、TSTO、AED在超重组内的水平明显高于非超重组(P＜0.05),未发现其余各组的激素水平与BMI指数具有相关性(P＞0.05)。结论 绝经后女性乳腺癌患者的血清性激素水平升高,血清E2、E1、AED水平升高可能是与绝经后女性乳腺癌的发病相关,BMI高的绝经后女性的血清性激素水平较高。     

Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC)

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend < or = 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.     

Urinary phytoestrogen excretion and breast cancer risk: evaluating potential effect modifiers endogenous estrogens and anthropometrics.

Steroid sex hormones play a central role in breast carcinogenesis. Evidence from in vitro and animal studies suggests that phytoestrogens may inhibit the development of mammary tumors through their role in regulating the synthesis, metabolism, and signal transduction of steroid hormones. In a study of 117 case-control pairs of postmenopausal women in Shanghai, we investigated whether the association between urinary phytoestrogen excretion and breast cancer risk may differ by levels of endogenous steroid sex hormones, sex hormone binding globulin (SHBG), body mass index (BMI), and waist:hip ratio (WHR). Fasting morning blood and urine samples were collected for the analysis of urinary isoflavonoids and mammalian lignans, as well as blood levels of SHBG and selected steroid hormones. For cancer patients, samples were collected before any cancer therapy. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals after adjusting for potential confounding factors. The inverse associations between urinary phytoestrogens and breast cancer risk were found to be more evident among women with a high BMI or WHR than those with a low level of these anthropometric measurements. Although a reduced risk of breast cancer was observed among women with a high excretion rate of urinary isoflavonoids in all of the strata defined by blood SHBG and steroid hormones, the inverse association was more pronounced among women with a high blood concentration of estradiol, a low level of estrone sulfate, or a low level of SHBG. The risks of breast cancer were also reduced with increasing excretion rate of mammalian lignans, although no test for a linear association was statistically significant in stratified analyses. Findings from this study suggest that the potential protective association of phytoestrogens may be modified by BMI, WHR, and blood levels of SHBG, and steroid hormones.     

Body size,body composition and endometrial cancer risk among postmenopausal women in UK Biobank

Previous studies on the association of adiposity with endometrial cancer risk have mostly used body mass index (BMI) as the main exposure of interest. Whether more precise measures of body fat, such as body fat percentage and fat mass estimated by bioimpedance analyses, are better indicators of risk than BMI is unknown. The role of central adiposity and fat-free mass in endometrial cancer development remains unclear. We used Cox regression models to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the associations of various measures of body size/composition with the risk of endometrial cancer among 135 110 postmenopausal women enrolled in UK Biobank. During a mean follow up of 6.8 years, 706 endometrial cancers were diagnosed, with a mean age at diagnosis of 65.5 years. The HRs (95% CIs) for endometrial cancer per 1 SD increase in BMI, body fat percentage and fat mass were broadly comparable, being 1.71 (1.61-1.82), 1.92 (1.75-2.11) and 1.73 (1.63-1.85), respectively. There was an indication of positive association between central adiposity, as reflected by waist circumference (HR_{per 1-SD increase} = 1.08, 95% CI: 1.00-1.17) and waist to hip ratio (HR_{per 1-SD increase} = 1.13, 95% CI: 1.01-1.26), and endometrial cancer risk after accounting for BMI. Fat-free mass was not an independent predictor of risk in this cohort. These findings suggest that body fat percentage and fat mass are not better indicators of endometrial cancer risk than BMI. Further studies are needed to establish whether central adiposity contributes to risk beyond overall adiposity.     

Serum sex hormones and breast cancer risk factors in postmenopausal women.

Postmenopausal women with elevated serum estrogens and androgens are at an increased risk of breast cancer. We evaluated associations of serum estrogen and androgen levels with age, anthropometry, and reproductive history to assess whether these characteristics could potentially modify breast cancer risk through hormonal mechanisms. A cross-sectional study was conducted among 133 postmenopausal women who donated blood to the serum bank (Columbia, MO) and served as controls in a previous prospective nested case control study of serum hormones and breast cancer risk. Standard regression methods were used to calculate adjusted means and test for trends in relationships of serum hormone concentrations with breast cancer risk factors. All analyses were performed on the log(e) scale, and all models included assay batch, date, and time of blood collection. Serum levels of estradiol, non-sex hormone binding globulin bound estradiol, estrone, estrone sulfate, and testosterone increased significantly with increasing body mass index (BMI), whereas sex hormone binding globulin levels decreased. After adjusting for BMI, nulliparous women tended to have higher testosterone levels compared with parous women (P = 0.05), but there was no evidence of a trend of decreasing testosterone with increasing parity. Dehydroepiandrosterone, its sulfate, and androstenediol decreased significantly with increasing age. Although BMI and parity could potentially modify breast cancer risk through hormonal mechanisms, age-related increases in breast cancer incidence do not appear to be mediated through changes in serum levels of the hormones evaluated.     

Body measurements, estrogen availability and the risk of human breast cancer: a case-control study.

Recent studies on lifestyle-related mechanisms involved in cardiovascular risk offer important clues for a better understanding of breast-cancer epidemiology. Central body-fat distribution promoted by an affluent dietary intake and a sedentary lifestyle over many years is related to elevated serum triglycerides and free fatty acids, with lower levels of sex-hormone-binding globulin (SHBG). The resulting greater availability of estradiol not bound to SHBG could help to explain the high breast-cancer incidence in Western industrialized countries. We conducted a case-control study comparing 225 women aged 38 to 75 years with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer who participated in a population-based breast-cancer screening program. Body fatness, as measured by body mass index (BMI), fat distribution as measured by waist-to-hip girth ratio (WHR), body height, serum lipids, SHBG and the available fraction of estradiol were analyzed in a conditional logistic regression, together with family history for breast cancer, reproductive history and smoking. Post-menopausal cases showed no difference in body fatness (BMI), but a significant preponderance of central adiposity (WHR). In contrast, pre-menopausal cases were significantly leaner, but had a similar body-fat distribution as compared with controls. In all women, WHR, and less strongly BMI, was positively correlated with serum levels of triglycerides and available estradiol fractions. An independent, positive linear correlation between body height and relative risk (RR) was observed. Moreover, a significant correlation between SHBG and menarcheal age was seen in cases, but not in controls. These data support our hypothesis that lifestyle relates to breast-cancer risk by metabolic-endocrine mechanisms which modulate the availability of individual sex-steroid concentrations in plasma. The findings of height as a risk factor and adult SHBG levels being correlated with menarcheal age suggest that lifestyle factors promoting breast-cancer development already act around puberty. The leanness of pre-menopausal cases awaits further explanation.     

Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal women

Elevated levels of circulating estrogens and androgens are linked to higher breast cancer risk among postmenopausal women; however, little is known about hormone levels within the breast. Hormone concentrations within the breast may not be reflected in the blood and are likely important contributors to breast carcinogenesis. We used a previously validated method to measure levels of estrone, estradiol, androstenedione, and testosterone in adipose tissue removed as part of breast excisions performed for cancer in 100 postmenopausal women (69 ER/PR +/+ and 31 ER/PR −/−) participating in a breast cancer case–control study. We also measured the same steroid hormones, as well as estrone sulfate, and sex hormone-binding globulin (SHBG) in serum from these patients and 100 controls matched on ages at blood collection and on menopause. Overall, concentrations of serum hormones did not vary significantly between controls and cases. However, women with ER−/PR− breast cancers had lower circulating levels of all measured sex steroid hormones and higher SHBG levels than women with ER+/PR+ breast cancers and controls. Similarly, hormone concentrations in breast adipose tissue were higher among women with ER+/PR+ compared to ER−/PR− breast cancer, although differences were only significant for testosterone. These data demonstrate that high sex steroid concentrations in both serum and adipose tissues are more strongly related to ER+/PR+ than ER−/PR− breast cancers. Measurement of sex hormones in serum and in the microenvironment may help in understanding the hormonal etiology of breast cancer, suggest methods for prevention, and have value in gauging treatment response and prognosis.     

Body fatness and sex steroid hormone concentrations in US men: results from NHANES III

Objective

Obesity is associated with a variety of chronic diseases, including cancer, which may partly be explained by its influence on sex steroid hormone concentrations. Whether different measures of obesity, i.e., body mass index (BMI), waist circumference, and percent body fat were differentially associated with circulating levels of sex steroid hormones was examined in 1,265 men, aged 20?C90+ years old, attending the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III).

Materials and methods

Serum hormones were measured by immunoassay. Weight, height, and waist circumference were measured by trained staff. Percent body fat was estimated from bioelectrical impedance. Multivariate linear regression was used to estimate associations between body fatness measures and hormone levels.

Results

Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all p trend < 0.05). The magnitude of change in these hormones was similar for a one-quartile increase in each body fatness measure.

Conclusion

Measured BMI, waist circumference, and percent body fat led to similar inferences about their association with hormone levels in men.     

Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin and SHBG (Sweden)

Objective: High levels of sex steroid hormones and prolactin have been suggested to enhance breast cancer development. Low levels of SHBG may indicate high levels of (bio-available) steroid hormones. The present study investigates whether high levels of sex steroid hormones and prolactin, and/or low levels of SHBG, are associated with high breast cancer risk. Methods: Blood samples were collected in about 65,000 women participating in two population-based prospective cohort studies in Sweden. Follow-up yielded 173 postmenopausal breast cancer cases who had not been exposed to HRT. Levels of estrone, estradiol, SHBG, FSH, prolactin, testosterone, androstenedione and DHEAs were analysed in cases and 438 controls. Logistic regression analysis yielded odds ratios (ORs), with 95% confidence intervals, adjusted for potential confounders. Results: The risk of breast cancer was associated with the highest versus lowest quartiles of estrone, OR: 2.58 (1.50–4.44), estradiol (dichotomised: high versus low) (1.73: 1.04–2.88), and testosterone (1.87: 1.08–3.25). High risks, although not statistically significant, were seen for androstenedione (1.58: 0.92–2.72) and DHEAs (1.62: 0.89–2.72). No strong associations were seen between SHBG or prolactin and risk of breast cancer. Conclusions: High levels of estrone, estradiol, testosterone, and possibly androstenedione and DHEAs, in postmenopausal women are associated with a high risk of subsequent breast cancer.     

Review of anthropometric factors and breast cancer risk.

Epidemiological evidence implicating anthropometric risk factors in breast cancer aetiology is accumulating. For premenopausal women, breast cancer risk increases with increasing height, but decreases with higher weight or body mass index, and no association with increased central adiposity exists. For postmenopausal women, an increased risk of breast cancer is found with increasing levels of all the anthropometric variables including height, weight, body mass index, waist-hip ratio, waist circumference and weight gain. Weight loss appears to decrease risk, particularly if it occurs later in life. Breast size may be a risk factor for breast cancer, however, the current evidence is inconclusive. Several hypothesized biologic mechanisms exist to explain how anthropometric factors influence breast cancer risk. Obesity may increase levels of circulating endogenous sex hormones, insulin and insulin-like growth factors that all, in turn, increase breast cancer risk. Genetic predisposition to obesity and to specific body fat distributions are also implicated. With obesity, there are increased levels of fat tissue that can store toxins and can serve as a continuous source of carcinogens. Recommendations for future research on anthropometric factors and breast cancer are provided. Sufficient evidence exists to support strategies to avoid weight gain throughout life as a means of reducing postmenopausal breast cancer risk.     

Obesity,body size,and risk of postmenopausal breast cancer: the Women's Health Initiative (United States)

OBJECTIVE: Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women.METHODS: We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50–79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993–1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference.RESULTS: Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) > 31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62–3.93), compared to slimmer women (baseline BMI 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88–2.01).CONCLUSIONS: Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.     

The effect of weight-loss on estimated breast-cancer risk and sex-hormone levels

The effect of weight loss on estimated breast cancer risk, sex hormone binding globulin (SHBG), total and free estradiol levels was evaluated. Increasing weight loss reduced upper body fat distribution progressively. Women with a family history of breast cancer who lost more than 7.0 kilograms decreased their estimated breast cancer risk by 25.7% while women without such a family history decreased their risk by 42.8%. A significant (P<0.001) increase in SHBG with a 4.0 to 7.4 kg weight loss was seen in both pre and postmenopausal women (P<0.05). No significant change in total or free estradiol levels was observed.     

Body size and composition and risk of postmenopausal breast cancer.

BACKGROUND: Studies of postmenopausal breast cancer have reported positive associations with body size and composition but it is uncertain whether these are due to non-adipose, adipose mass, or central adiposity, and whether they are limited to subgroups defined by age or tumor characteristics.METHODS: In a prospective cohort study of women ages 27 to 75, body measurements were taken directly; fat mass and fat-free mass being estimated by bioelectrical impedance analysis, and central adiposity by waist circumference. Among 13,598 women followed on average for 9.1 years, 357 invasive breast cancers were ascertained via the population cancer registry. Data were obtained on estrogen receptor and progesterone receptor status, grade, and stage.RESULTS: Estimates of body size such as fat-free mass [hazard ratio per 10 kg increase = 1.45, 95% confidence interval (CI) 1.16-1.82], fat mass (hazard ratio per 10 kg increase = 1.18, 95% CI, 1.06-1.31), and waist circumference (hazard ratio per 10 cm increase = 1.13, 95% CI, 1.03-1.24) were associated with breast cancer risk. There was no association with risk before 15 years postmenopause. About 15 years after menopause, risk increased sharply and remained elevated. There was some evidence that this association might be stronger for estrogen receptor-positive and poorly differentiated tumors but no evidence that it differed by stage.CONCLUSION: Given that elements of body size and composition are positively associated with breast cancer risk, although not until 15 or more years postmenopause, it is possible that women could reduce risk by maintaining ideal body weight after menopause.