Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants.

PURPOSE: To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene. PATIENTS AND METHODS: Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model. RESULTS: Overall, women with the highest one-third estradiol levels (> or = 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P <.05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P =.005 and P =.015, respectively). CONCLUSION: The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen.     

Physical activity and breast cancer risk among Asian-American women in Los Angeles: a case-control study

BACKGROUND: To the authors' knowledge, there have been few studies published to date regarding physical activity patterns and breast cancer risk in Asian and Asian-American women. METHODS: The authors conducted a population-based case-control study of 501 Asian-American women with incident breast cancer and a control group of 594 Asian-American women in Los Angeles County to evaluate the role of lifetime physical activity on breast cancer risk. Information concerning lifetime recreational physical activity (i.e., type of activity, duration [years], and frequency [average hours per week]) and occupational physical activity was obtained using a structured questionnaire that was administered in person. RESULTS: Increasing years and levels (average metabolic equivalent [MET] hours per week) of lifetime recreational activity were associated with a significantly reduced risk of breast cancer after adjusting for demographic factors, migration history, and menstrual and reproductive factors. Compared with women who had no lifetime recreational physical activity, 3-6 MET hours per week, > 6-12 MET hours per week, and > 12 MET hours per week of activity were associated with significantly reduced risk, with odds ratios (and 95% confidence intervals) of 0.91 (0.55-1.49), 0.65 (0.39-1.10), 0.53 (0.31-0.90), and 0.47 (0.28-0.80), respectively (P value for trend < 0.001). The risk of breast cancer was associated inversely with occupational physical activity, although the result was not statistically significant. CONCLUSIONS: The findings of the current study provide further support for the finding that physical activity has a protective role in breast cancer.     

Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women

Objective Lifetime cumulative number of menstrual cycles is related to breast cancer risk. The aim of this study is to investigate the relation between this index and serum sex hormone levels in postmenopausal women. Methods Cross-sectional study including 860 naturally postmenopausal Dutch participants of the European Prospective Investigation into Cancer and Nutrition. Lifetime cumulative number of menstrual cycles was computed using questionnaire data on ages at menarche and menopause, number of pregnancies, breastfeeding, oral contraceptive use (OC) and regularity pattern. Measurements of hormones included estrone (E1), estradiol (E2), andostrenedione, testosterone, sex-hormone binding globulin (SHBG) and dehydroepiandrostenedione sulfate (DHEAS). The relation between the lifetime cumulative number of menstrual cycles and hormone levels was assessed using analysis of covariance. Relations between reproductive characteristics and hormone levels were also studied. Adjustments for characteristics at blood collection included age, years since menopause, BMI, hormone replacement therapy use, OC use, smoking habits, alcohol intake and physical activity were done. Results Lifetime cumulative number of cycles was related with SHBG; participants in the lowest category had higher SHBG levels. For the separate characteristics, DHEAS and androstenedione increased significantly with increasing age at menarche, while androstenedione and testosterone decreased with increasing age at menopause. For the parity characteristics, SHBG levels increased according to the number of live births. Conclusions Lifetime cumulative number menstrual cycles was related only to SHBG. Therefore, free levels of estrogens or androgens may be related to this number of menstrual cycles estimate, reflecting lifetime exposure to ovarian hormones.     

Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study

The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence, we analyzed data from the Shanghai Breast Cancer Study, a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews were completed for 1,459 women newly diagnosed with breast cancer between ages 25 and 64 and for 1,556 controls frequency-matched to cases by age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) related to menstrual and reproductive factors. Earlier menarcheal age, nulliparity, and later age at first live birth were associated with increased risk of breast cancer among both pre- and post-menopausal women, while never having breast-fed and later age at menopause were associated with elevated risk only among post-menopausal women. Among controls, 32% of younger women (40 years) reported starting menarche at age of 13 or younger, and this factor contributed to 44% of cases diagnosed among younger women and 26% to 28% of cases in older women. Older age at first live birth or at menopause explained a considerable portion of cases diagnosed in older, but not younger, women. Our study suggests that the changes in menstrual and reproductive patterns among women in Shanghai have contributed to the recent increase in breast cancer incidence, particularly among younger women.     

Role and impact of menstrual and reproductive factors on breast cancer risk in Japan.

The aim of this study was to clarify the role and impact of menstrual and reproductive factors in relation to breast cancer and its hormone receptor-defined subtype, overall and separately among premenopausal and postmenopausal women in a low-risk population, using data from the Japan Public Health Center-based Prospective study. A total of 55 537 women aged 40-69 years completed a self-administered questionnaire, which included items about menstrual and reproductive history. During 1990-2002, 441 newly diagnosed cases of breast cancer were identified. Early age at menarche for premenopausal women, late age at natural menopause, nulliparity and low parity for both premenopausal and postmenopausal women, and late age at first birth for postmenopausal women were significantly associated with an increased risk of breast cancer. No overall significant associations were seen between the use of exogenous female hormones or breast feeding and breast cancer risk. Age at menarche and age at natural menopause were somewhat more closely associated with the risk of progesterone receptor-negative than positive breast cancer although no difference was observed for estrogen receptor status. Risks associated with parity, number of births and age at first birth did not significantly differ by hormone receptor-defined breast cancer. Our findings suggest that menstrual and reproductive factors may play an important role in the development of breast cancer among low-risk populations, similarly as they do in Western populations, and that risk factors might differ by hormone receptor status.     

Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer. PATIENTS AND METHODS: Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women. RESULTS: Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women. CONCLUSIONS: The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.     

Does hormone therapy counter the beneficial effects of physical activity on breast cancer risk in postmenopausal women?

Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether this association is stronger among non-hormone users or former users of menopausal hormone therapy (HT) is of interest given the marked decline in HT use since 2002. The Women's Contraceptive and Reproductive Experiences Study, a population-based case-control study of invasive breast cancer, recruited white women and black women ages 35-64 years and collected histories of lifetime recreational physical activity and HT use including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT). Among postmenopausal women (1,908 cases, 2,013 control participants), breast cancer risk declined with increasing levels of lifetime physical activity among never HT users; among short-term HT users (fewer than 5 years); and among current ET users; P (trend) values ranged from 0.004 to 0.016. In contrast, physical activity had no significant association with risk among long-term and past HT users and among current EPT users. No statistical evidence of heterogeneity was demonstrated for duration or currency of HT use. Breast cancer risk decreases with increasing lifetime physical activity levels among postmenopausal women who have not used HT, have used HT for less than 5 years, or are current ET users, yet this study was unable to demonstrate statistically that HT use modifies the relationship between physical activity and breast cancer. With profound changes in HT use occurring since 2002, it will be important in future studies to learn whether or not any association between physical activity and breast cancer among former HT users is a function of time since last HT use.     

Lifetime Physical Activity and Breast Cancer a Case-Control Study in Kelantan,Malaysia

Background Physical inactivity has been identi ed as the fourth leading risk factor for global mortality and is associated with increased breast cancer diagnosis and recurrence. Purpose To examine the association between adult lifetime physical activity and breast cancer risk in a case-control analysis. Materials and Methods This study involved 122 cases of breast cancer and 121 controls in the state of Kelantan in Malaysia. A comprehensive measure of lifetime physical activity was used to assess occupational, household, and recreational/sports activity. For every type of activity, a metabolic equivalent (MET) score was assigned using the compendium of physical activities. MET-hours/week per year for all types of activities at different levels of intensities for different age groups were calculated. Logistic regression analysis was used to estimate odds ratios between various measures of physical activity and breast cancer risk. Conclusions The mean MET-hours/week per year for all activities were 120.0 and 132.9 of MET-hours/week per year for cases and controls respectively. Household activities accounted about 70% of the total lifetime physical activities. Only about 2.5% of the total lifetime physical activities were in the form of recreational/sports. This study found no association between lifetime occupational and recreational/sports physical activities with breast cancer risk among the Kelantanese women. However, higher intensity lifetime household activities seemed to signi cantly reduce risk of breast cancer.     

Association of physical activity with reproductive hormones: the Penn Ovarian Aging Study.

BACKGROUND: Physical activity is associated with reduced risk for breast cancer, perhaps through reductions in circulating reproductive hormones (estrogens and androgens). There may also be a role for physical activity in regulating menopausal symptoms. Few studies have examined associations of physical activity on hormone levels. None have examined the potential effect of the menopausal transition on the associations between physical activity and reproductive hormone levels. MATERIALS AND METHODS: Data from the Penn Ovarian Aging Study were used for this analysis. Self-reported physical activity was assessed in 391 women up to four times over 10 years and extending across the menopausal transition. Other assessments included reproductive hormones via RIA (estradiol, luteinizing hormone, follicle-stimulating hormone, testosterone, DHEA sulfate), body weight, and height. Multivariate repeated measures regression models were developed to compare reproductive hormone levels within physical activity tertiles, adjusting for age, follow-up time, smoking, and ethnicity. RESULTS: Activity level was inversely associated with estradiol in the subgroup in the late transition stage. Adjusted means for estradiol were 24.6 and 37.9, a relative difference of 54% in estradiol when comparing highest to lowest activity tertile (P = 0.02). Similarly, in this subgroup, there was an inverse association between physical activity and testosterone levels (means of 11.1 and 15.94 in the highest and lowest tertile, a 47% relative difference; P = 0.01). There were no significant associations of activity with any other reproductive hormone. CONCLUSIONS: These results identify a particular window of the menopausal transition during which physical activity is associated with reduced estradiol and/or testosterone levels.     

Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.     

Postmenopausal breast cancer risk and cumulative number of menstrual cycles.

OBJECTIVE: To explore whether the lifetime cumulative number of menstrual cycles, as an index for total exposure to endogenous estrogens, and the number of menstrual cycles until a first full-term pregnancy (FFTP), are associated with breast cancer risk in postmenopausal women. METHODS: Population-based study with data from the Prospect-European Prospective Investigation into Cancer and Nutrition study. Naturally menopausal participants were eligible (n = 6,718). The cumulative number of menstrual cycles was computed in 6,031 (90%) women. We calculated the number of cycles until FFTP among parous participants. The number of menstrual cycles was impossible to compute in women who reported to be always irregular; therefore, we added the "always irregular" category in the analysis. During the 46,746 person-years of follow-up, 168 breast cancer cases were identified. Cox regression models were used and adjustments were made to account for potential confounders. RESULTS: Even when our data does not show a clear linear gradient, we observed an increased breast cancer risk in women with a higher number of cumulative menstrual cycles in their lifetime. Using < or = 415 cycles as reference, the hazard ratio for the irregular group, 416-453, 454-490, and > or = 491 cycles was 1.11 (.56, 2.19), 1.88 (1.14, 3.12), 1.74 (1.05, 2.87), and 1.80 (1.09, 2.96), respectively. Although not statistically significant, and of less magnitude, the risk estimates for the number of cycles before FFTP showed the same tendency. CONCLUSION: Among women who underwent natural menopause, a higher number of menstrual cycles in lifetime, reflecting a longer exposure to endogenous estrogens, is associated with an increased breast cancer risk.     

The international variation in breast cancer rates: An epidemiological assessment

Part of the international differences in breast cancer incidence rates can be explained by geographic variation in reproductive and other breast cancer risk factors. Age at menarche and age at onset of regular ovulatory menstrual cycles are two such factors; both vary across populations directly according to breast cancer risk, and both are acknowledged as breast cancer risk factors. Consideration of the body of evidence on these factors, as well as that on age at menopause, suggests that the cumulative frequency of ovulatory menstrual cycles is a critical determinant of breast cancer risk. Although age at first term pregnancy explains the majority of the protective effect of parity on breast cancer risk, two recent studies have demonstrated a small residual protective effect of increasing number of births. It appears that pregnancy hasparadoxical effects on breast cancer risk in terms of hormone production and metabolism. The initial effect is an increased risk associated with first trimester estrogen exposure. However, the hormonal consequences of completing the pregnancy counteract this negative effect of early pregnancy. The effect of body weight, a breast cancer risk factor for postmenopausal women, can be explained in terms of increased extraglandular conversion of androstenedione to estrone. Further evidence supporting a pathogenic role of estrogens in the development of breast cancer comes from international studies of endogenous hormones in populations with differing risks of breast cancer. These risk factors have been incorporated into a mathematical model which is based on the concept that breast tissue ages according to hormonal (primarily estrogen) exposure; this model closely predicts the incidence rates throughout the world.     

The international variation in breast cancer rates: An epidemiological assessment

Part of the international differences in breast cancer incidence rates can be explained by geographic variation in reproductive and other breast cancer risk factors. Age at menarche and age at onset of regular ovulatory menstrual cycles are two such factors; both vary across populations directly according to breast cancer risk, and both are acknowledged as breast cancer risk factors. Consideration of the body of evidence on these factors, as well as that on age at menopause, suggests that the cumulative frequency of ovulatory menstrual cycles is a critical determinant of breast cancer risk. Although age at first term pregnancy explains the majority of the protective effect of parity on breast cancer risk, two recent studies have demonstrated a small residual protective effect of increasing number of births. It appears that pregnancy hasparadoxical effects on breast cancer risk in terms of hormone production and metabolism. The initial effect is an increased risk associated with first trimester estrogen exposure. However, the hormonal consequences of completing the pregnancy counteract this negative effect of early pregnancy. The effect of body weight, a breast cancer risk factor for postmenopausal women, can be explained in terms of increased extraglandular conversion of androstenedione to estrone. Further evidence supporting a pathogenic role of estrogens in the development of breast cancer comes from international studies of endogenous hormones in populations with differing risks of breast cancer. These risk factors have been incorporated into a mathematical model which is based on the concept that breast tissue ages according to hormonal (primarily estrogen) exposure; this model closely predicts the incidence rates throughout the world.     

Benign and malignant breast disease: initial study results of serum and breast fluid analyses of endogenous estrogens

Design, methods, and study population of a long-term multidisciplinary investigation of benign and malignant breast disease were reported. This initial report focused on the relation of menstrual, reproductive, and other factors to serum and breast fluid estrogen measures [estradiol (E2), estrone (E1), percent free estrogen, and sex hormone binding globulin] among control women. After adjustment for the factors found to be related to the various estrogen measures, estrogen levels in women with benign and malignant disease were compared to those of controls. Findings were as follows: a) little evidence of any relation of most breast cancer risk factors with the various serum estrogen parameters studied; b) differences in breast fluid estrogen levels that may be relevant to the protective effect of parity on breast cancer risk; c) markedly higher levels of E2 and E1 in breast fluid than in serum and no evidence of a correlation of serum with breast fluid measures; d) no support for the hypothesis that breast cancer patients have higher serum percent free E2 than controls or women with benign breast disease; and e) higher breast fluid E2 and E1 levels in women with biopsied benign breast disease than in controls.     

Usual physical activity and endogenous sex hormones in postmenopausal women: the European prospective investigation into cancer-norfolk population study.

BACKGROUND: Short-term trials indicate that intensive physical activity may influence endogenous sex hormone concentrations. However, the relationship between usual daily physical activity and endogenous hormones in postmenopausal women in the general population is still uncertain. OBJECTIVE AND METHODS: To determine the relationship between usual physical activity and endogenous sex hormones in postmenopausal women. A cross-sectional population-based study of 2,082 postmenopausal women ages 55 to 81 years, residing in the general community of Norfolk, United Kingdom, and not currently using hormone replacement therapy were chosen to participate. Physical activity in the past 1 year was assessed using a validated questionnaire, and endogenous sex hormone and sex hormone-binding globulin (SHBG) concentrations were determined. RESULTS: Usual physical activity levels were inversely associated with circulating concentrations of testosterone and estradiol, testosterone/SHBG ratio, and positively associated with SHBG. These associations were only slightly attenuated after adjusting for potential covariates including body mass index, smoking status, alcohol intake, and reproductive variables. Testosterone concentrations and testosterone/SHBG ratios were 19% [95% confidence interval (95% CI), 9-27%, P < 0.001] and 24.0% (95% CI, 13-34% P < 0.001) lower, respectively, whereas estradiol concentrations were 6% (95% CI, 0-12%; P < 0.05) lower in the highest compared with lowest activity levels, respectively. A decreasing trend for the estradiol/SHBG ratio and 17alpha-hydroxyprogesterone concentrations was also observed. Androstenedione levels did not differ significantly according to physical activity. CONCLUSIONS: Higher usual physical activity levels among postmenopausal women seem to be related to lower endogenous testosterone and estradiol concentrations. This may be one mechanism that could partly explain the reported inverse relationship between physical activity and breast cancer risk in some studies.     

Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.

We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR=0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.     

Circadian Disruption, Shift Work and the Risk of Cancer: A Summary of the Evidence and Studies in Seattle

There is increasing interest in the possibility that disruption of normal circadian rhythm may increase the risk of developing cancer. Persons who engage in nightshift work may exhibit altered nighttime melatonin levels and reproductive hormone profiles that could increase the risk of hormone-related diseases, including breast cancer. Epidemiologic studies are now beginning to emerge suggesting that women who work at night, and who experience sleep deprivation, circadian disruption, and exposure to light-at-night are at an increased risk of breast cancer, and possibly colorectal cancer as well. Several studies have been conducted in Seattle recently to investigate the effects of factors that can disrupt circadian rhythm and alter normal nocturnal production of melatonin and reproductive hormones of relevance to breast cancer etiology. Studies completed to date have found: (1) an increased risk of breast cancer associated with indicators of exposure to light-at-night and night shift work; and (2) decreased nocturnal urinary levels of 6-sulphatoxymelatonin associated with exposure to 60-Hz magnetic fields in the bedroom the same night, and a number of other factors including hours of daylight, season, alcohol consumption and body mass index. Recently completed is an experimental crossover study designed to investigate whether exposure to a 60-Hz magnetic field under controlled conditions in the home sleeping environment is associated with a decrease in nocturnal urinary concentration of 6-sulphatoxymelatonin, and an increase in the urinary concentration of luteinizing hormone, follicle stimulating hormone, and estradiol in a sample of healthy women of reproductive age. Presently underway is a study to determine whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased urinary concentrations of the reproductive hormones listed above in a sample of healthy women of reproductive age, and to elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified. A proposal is under review to extend these studies to a sample of healthy men to investigate whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased concentrations of urinary cortisol and cortisone, urinary levels of a number of androgen metabolites, and serum concentrations of a number of reproductive hormones. Secondarily, the proposed study will elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified, as well as investigate whether polymorphisms of the genes thought to regulate the human circadian clock are associated with the ability to adapt to night shift work. It is anticipated that collectively these studies will enhance our understanding of the role of circadian disruption in the etiology of cancer.     

Does the increase of endogenous steroid hormone levels also affect breast cancer risk in Chinese women? A case–control study in Chongqing,China

Accumulating epidemiological evidence suggests that sex steroid hormones are positively associated with the development of breast cancer. However, most of these studies were conducted among Caucasian women and few have been carried out in China. To determine whether the associations of sex steroid hormone levels with breast cancer risk observed by and large in Caucasian populations are also evident in Chinese women, we conducted a case–control study in Chongqing, China. The study included 367 incident breast cancer patients and 367 healthy controls matched on menstrual status, age and periods of blood collection in the menstrual cycle. Plasma concentrations of estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were determined by electrochemiluminescene immunoassay (ECLIA). Conditional logistic regression analysis was performed to examine their associations with breast cancer risk. From comparisons of upper and lower tertiles, we observed statistically significant positive associations with breast cancer risk for plasma estradiol levels in follicular phase (adjusted odds ratio [OR] = 5.48, 95% confidence interval [CI] = 1.58–18.97), luteal phase (OR = 4.23, CI = 1.65–10.87) and postmenopausal (OR = 2.67, CI = 1.20–5.93); for progesterone levels in luteal phase (OR = 3.11, CI = 1.28–7.56), and for testosterone levels in postmenopausal (OR = 2.83, CI = 1.26–6.35). No significant association was found with DHEAS or SHBG. Our study suggests that high circulating levels of estradiol and testosterone are positively associated with increased breast cancer risk in Chinese women, which are generally consistent with the observations in Caucasian populations. © 2008 Wiley‐Liss, Inc.     

Leisure-time physical activity in relation to breast cancer among young women (Washington, United States)

It has been hypothesized that women who participate in vigorous physical activity may have lower risk of breast cancer due to lower lifetime exposure to ovarian hormones. A population-based case-control study was conducted to investigate the association between leisure-time physical activity and risk of breast cancer among women aged 21 to 45 years. Cases were 747 women diagnosed with invasive breast cancer between 1983 and 1990 in three counties of western Washington state (United States), and were identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry. Controls were 961 women selected from the same area by random-digit telephone dialing. Physical activity was assessed through personal interview, with questions on frequency and duration of each type of recreational activity during the two-year period immediately prior to reference date (date of diagnosis for cases and a comparable assigned date for controls) and between ages 12 and 21. For the two-year time period before diagnosis, there was no association with frequency of activity (age-adjusted odds ratio [OR]=0.93, 95 percent confidence interval [CI]=0.71-1.22 for four or more episodes per week cf none), total hours spent in physical activity (age-adjusted OR=0.92, CI=0.71-1.22 for four or more hours per week cf none) or MET (metabolic equivalent energy expenditure unit) (age-adjusted OR=0.95, CI=0.73-1.23 for 18 or more METs per week cf none), nor any trend in risk with increasing activity levels. Similarly, there was no association between leisure activity during adolescence and breast cancer risk. These results were not confounded further by body mass index (wt/ht2), age at menarche, age at first full-term pregnancy, parity, family history of breast cancer, or other measured health behaviors. Our findings do not support a protective effect of leisure-time physical activity either in the adolescent years or in adulthood on breast cancer in young women.     

Energetic factors, ovarian steroids and the risk of breast cancer.

In industrial countries, women often have excess metabolic energy due to high food consumption and low physical activity. High lifetime energy availability results in high lifetime levels of ovarian steroid hormones. Oestrogens and progesterone are hypothesized to play a crucial role in the development and prognosis of breast cancer. Epidemiological studies document the importance of physical activity and caloric limitations in reducing breast cancer risk. The risk of breast cancer is much higher in industrial countries than in developing countries, where women are characterized by lower energy intake and higher energy expenditure. It is likely, that the beneficial effects of physical activity and of negative energy balance are mediated by the reduced levels of ovarian steroids. While both weight loss and physical activity may have similar efficacy in suppressing ovarian function and, therefore, in reducing the risk of breast cancer, we suggest that it may be more advantageous for premenstrual women to achieve lifetime reduction in steroid levels by increasing their physical activity, rather than by weight loss due to caloric restriction alone.