Soy isoflavone intake and breast cancer risk in Japan: From the Takayama study

The effects of soy or isoflavone intake on breast cancer need to be examined further in epidemiologic studies. We assessed the associations of soy and isoflavone intake with breast cancer incidence in a population‐based prospective cohort study in Japan. Participants were members from the Takayama study, aged 35 years or older in 1992. The follow‐up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008. Cancer incidence was mainly confirmed through regional population‐based cancer registries. Breast cancer was defined as code C50 according to ICD‐10. Soy and isoflavone intakes were assessed with a validated food frequency questionnaire. Using the Cox proportional hazard models, the association of soy and isoflavone intake with breast cancer was assessed after adjustments for age, body mass index, physical activity, smoking, alcohol consumption, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy. Among the 15,607 women analyzed, 172 had developed breast cancer. The relative risks of postmenopausal breast cancer were lower among women with higher intakes of soy (trend p = 0.023) and isoflavone (trend p = 0.046), although the relative risks of premenopausal breast cancer were not associated with intakes of soy and isoflavone. Decreased risks of breast cancer were found even among women with a moderate intake of soy and isoflavone. These results suggested that soy and isoflavone intakes have a protective effect on postmenopausal breast cancer.     

Dietary advanced glycation end products and cancer risk in Japan: From the Takayama study

Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site‐specific cancers in a population‐based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE N ^ε‐carboxymethyl‐lysine (CML) was estimated using databases of CML content in foods determined using ultraperformance liquid chromatography–tandem mass spectrometry. Cancer incidence was confirmed through regional population‐based cancer registries. During a mean follow‐up period of 13.3 years, 1954 men and 1477 women developed cancer. We did not observe a significant association between CML intake and the risk of total cancer in men or women. In men, compared with the lowest quartile of CML intake, the hazard ratios of liver cancer for the second, third, and highest quartiles were 1.69 (95% CI: 0.92–3.10), 1.48 (95% CI: 0.77–2.84), and 2.10 (95% CI: 1.10–3.98; trend p = 0.04). Conversely, a decreased relative risk of male stomach cancer was observed for the second and highest quartiles of CML intake versus the lowest quartile, with hazard ratios of 0.73 and 0.67, respectively (trend p = 0.08). Our finding on the potential harmfulness of consuming AGEs on liver cancer risk is intriguing and warrants further study.     

Soy isoflavone intake and stomach cancer risk in Japan: From the Takayama study

Although several experimental studies suggested that soy isoflavone intake inhibits the growth of stomach cancer, previous epidemiological studies have observed inconsistent results. We evaluated the associations of soy or isoflavone intake with stomach cancer incidence after considering several lifestyle factors, including salt intake, in a population‐based prospective cohort study in Japan. Subjects were 14,219 men and 16,573 women aged 35 years or older in September 1992. Soy and isoflavone intakes, assessed with a validated food‐frequency questionnaire, were controlled for the total energy intake. Cancer incidence was mainly confirmed through regional population‐based cancer registries. Until March 2008, 441 men and 237 women developed stomach cancer. After adjustments for multiple confounders, a significantly decreased relative risk of stomach cancer was observed in the highest vs. lowest quartile of soy intake; the estimated hazard ratios were 0.71 (95% CI: 0.53, 0.96) for men (p for trend = 0.039) and 0.58 (95% CI: 0.36, 0.94) for women (p for trend = 0.003). Similar inverse associations between isoflavone intake and stomach cancer risk were also observed in women. Higher intake of non‐fermented soy foods was significantly associated with a lower risk of stomach cancer (p for trend: 0.022 in men and 0.005 in women), whereas there was no significant association between the intake of fermented soy foods and a risk of stomach cancer. These results suggest that a high intake of soy isoflavone, mainly nonfermented soy foods, have a protective effect against stomach cancer.     

Dietary melatonin and liver cancer incidence in Japan: From the Takayama study

There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population-based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography–tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow-up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin-containing foods might play a role in the prevention of liver cancer.     

Meat consumption and colorectal cancer risk in Japan: The Takayama study

Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population‐based prospective cohort study in Japan. Participants were 13 957 men and 16 374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population‐based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest versus lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03, 1.79) for total meat (P for trend = 0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (P for trend = 0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer.     

Active cigarette smoking and risk of breast cancer

Although epidemiological evidence on the role of active cigarette smoking in breast cancer risk has been inconsistent, recent literature supports a modest association between smoking and breast cancer. This association is particularly observed in women who smoke for a long duration, or who smoke for a long time prior to their first pregnancy. Here, we provide updated results on cigarette smoking and breast cancer risk in the Canadian National Breast Screening Study (NBSS). The NBSS is a large cohort of 89,835 women, aged 40–59, who were followed for a mean of 22.1 years, resulting in the ascertainment of 6,549 incident cases of breast cancer. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cigarette smoking variables with breast cancer risk. We found breast cancer to be associated with duration (40 years vs. 0: HR = 1.57; 95%CI = 1.29–1.92), intensity (40 cigarettes per day vs. 0: HR = 1.21; 95%CI = 1.04–1.40), cumulative exposure (40 pack‐years vs. 0: HR = 1.19; 95%CI = 1.06–1.13) and latency (40 years since initiation vs. 0: HR = 1.19; 95%CI = 1.10–1.53) of cigarette smoking. Number of years smoked prior to first full‐term pregnancy was associated with higher risk of breast cancer than comparative years smoked post‐pregnancy (among parous women, 5 years pre pregnancy vs. 0: HR = 1.18; 95%CI = 1.10–1.26). These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.     

Chemical exposures in the workplace and breast cancer risk: A prospective cohort study

We investigated the relationship between workplace chemical exposures and breast cancer risk among women enrolled in the Sister Study, a prospective cohort study of US and Puerto Rican women. A total of 47,640 participants reported work outside of the home. Workplace exposure to eleven agents (acids, dyes or inks, gasoline or other petroleum products, glues or adhesives, lubricating oils, metals, paints, pesticides, soldering materials, solvents and stains or varnishes) was characterized based on self‐reports of frequency and duration of use. Approximately 14% of the study population reported exposure to only one agent and 11% reported working with two or more of the 11 agents in their lifetime. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for each agent, adjusting for established breast cancer risk factors. During follow‐up, 1,966 cases of breast cancer were reported. Although there were no significant associations between ever use of the eleven agents evaluated and breast cancer risk, women with cumulative exposure to gasoline or petroleum products at or above the highest quartile cutoff had an elevated risk of total (HR: 2.3, 95%CI: 1.1–4.9) and invasive (HR: 2.5, 95%CI: 1.1–5.9) breast cancer compared with women in the lowest quartile group (p_trend = 0.03). Workplace exposure to soldering materials was associated with an increased risk of premenopausal breast cancer (HR = 1.8, 95% CI = 1.1–3.0). Findings support the need for further studies to elucidate the role of occupational chemicals in breast cancer etiology.     

Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort

There are several biologic mechanisms whereby coffee might reduce breast cancer risk. Caffeine and caffeic acid, major coffee constituents, have been shown to suppress mammary tumor formation in animal models and to inhibit DNA methylation in human breast cancer cells, respectively. Coffee may also reduce risk through decreasing inflammation and influencing estrogen metabolism. However, epidemiologic studies have been inconsistent and few studies have examined the association by estrogen and progesterone receptor (ER/PR) status. We evaluated coffee intake for its effect on incident breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort, which included 198,404 women aged 50-71 with no history of cancer, who in 1995-1996 completed a questionnaire capturing usual coffee intake over the past year. State cancer registry and mortality index linkage identified 9,915 primary incident breast carcinomas through December 2006; available information on hormone receptor (HR) status identified 2,051 ER+/PR+ and 453 ER-/PR- cancers. In multivariable proportional hazards models, coffee intake was not associated with breast cancer risk (p-value for trend = 0.38; relative risk = 0.98, 95% confidence interval: 0.91-1.07, for four or more cups per day as compared to women who never drank coffee), and results did not vary by body mass index or history of benign breast biopsy (p-value for interaction > 0.10). We found no evidence of a relationship with either caffeinated or decaffeinated coffee. Null findings persisted for risk of both HR-positive and -negative breast cancers. These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis.     

Cigarette smoking and breast cancer risk: a population-based study in Sweden

In a Swedish population-based case-control study, smoking showed no convincing association with risk of postmenopausal breast cancer - regardless of timing or level of smoking exposure - either overall or among subgroups.     

Association between ambient air pollution and breast cancer risk: The multiethnic cohort study

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NO_x, NO₂, PM₁₀, PM_2.5), land use regression (LUR, NO_x, NO₂) and California Line Source Dispersion model (CALINE4, NO_x, PM_2.5) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993–1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NO_x (per 50 parts per billion [ppb]) and NO₂ (per 20 ppb) determined by kriging and LUR and with PM_2.5 and PM₁₀ (per 10 μg/m³) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NO_x (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02–1.79), NO₂ (HR = 1.44, 95% CI: 1.04–1.99), PM₁₀ (HR = 1.29, 95% CI: 1.07–1.55) and PM_2.5 (HR = 1.85, 95% CI: 1.15–2.99) determined by kriging and NO_x (HR = 1.21, 95% CI:1.01–1.45) and NO₂ (HR = 1.26, 95% CI: 1.00–1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NO_x and NO₂ among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted.     

Education and risk of breast cancer in the Norwegian-Swedish women's lifestyle and health cohort study

A positive relationship between level of education and female breast cancer risk is well supported by scientific evidence, but few previous studies could adjust for all relevant potential confounding factors. The authors' purpose was to examine how risk for breast cancer varies with level of education and to identify factors that explain this variation, using data from a prospective cohort study including 102860 women from Norway and Sweden who responded to an extensive questionnaire in 1991/1992; 1090 incident primary invasive breast cancer cases were revealed during follow-up, which ended in December 1999. The Cox Proportional Hazards Model was used to calculate relative risks (RR) with 95% confidence intervals (CI). Women with more than 16 years of education had a 36% increased risk compared to the lowest educated (7-9 years) (Age adjusted RR=1.36, 95% CI: 1.10, 1.68). This relationship was slightly stronger among postmenopausal (RR 1.51) than among premenopausal (RR 1.25) women. In both groups, however, the relative risk estimates turned close to unity by adjustment for parity, age at first birth, body mass index (BMI), height, age at menarche, menopausal status, use of oral contraceptives and consumption of alcohol. The overall multivariate relative risk among the highest educated women was 1.04 (95% CI 0.82-1.32). The results of our study suggest a clear positive gradient in risk for breast cancer by level of education, which can be fully explained by established breast cancer risk factors.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.     

Glycemic load,glycemic index and breast cancer risk in a prospective cohort of Swedish women

High‐glycemic load diets have been hypothesized to increase the risk of breast cancer but epidemiologic studies have yielded inconsistent findings. We examined the associations of carbohydrate intake, glycemic index and glycemic load with risk of overall and hormone receptor‐defined breast cancer in the Swedish Mammography Cohort, a population‐based cohort of 61,433 women who completed a food frequency questionnaire at enrollment in 1987–1990. During a mean follow‐up of 17.4 years, we ascertained 2,952 incident cases of invasive breast cancer. Glycemic load but not carbohydrate intake or glycemic index was weakly positively associated with overall breast cancer risk (p for trend = 0.05). In analyses stratified by estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors, we observed statistically significant positive associations of carbohydrate intake, glycemic index and glycemic load with risk of ER+/PR? breast cancer; the multivariate relative risks comparing extreme quintiles were 1.34 [95% confidence interval (CI) = 0.93–1.94; p for trend = 0.04] for carbohydrate intake, 1.44 (95% CI = 1.06–1.97; p for trend = 0.01) for glycemic index and 1.81 (95% CI = 1.29–2.53; p for trend = 0.0008) for glycemic load. No associations were observed for ER+/PR+ or ER?/PR? breast tumors. These findings suggest that a high carbohydrate intake and diets with high glycemic index and glycemic load may increase the risk of developing ER+/PR? breast cancer. © 2009 UICC     

Passive smoking and breast cancer risk among non-smoking Chinese women

Our purpose was to evaluate whether passive exposure to cigarette smoke may be related to breast cancer risk. Data from the Shanghai Breast Cancer Study, a large population-based study of 1459 breast cancer cases and 1556 controls aged 25-64 years, were analyzed. Respective response rates were 91.1% and 90.3%. Passive smoking questions were added to all face-to-face interviews 7 months into the study. Women were asked about exposure to their husbands' smoke at home as well as exposure in the workplace. Analyses were restricted to the 1013 cases and 1117 controls with passive tobacco smoke exposure data who had never actively smoked. Over 60% of controls reported some exposure to a husband's smoke and over 40% reported exposure to passive smoke in the workplace. Overall, there was no apparent association between any passive smoke exposure or exposure to a husband's smoke and breast cancer risk. There was some evidence of an elevated breast cancer risk associated with passive smoking exposure of 5 hr or more per day in the workplace (OR = 1.6, 95% confidence interval 1.0-2.4; p for trend = 0.02). This association warrants further investigation.     

Increased risk of second cancers following breast cancer: Role of the initial treatment

Objectives and methods.The risk of second primary malignancies (SMN) was studied in a cohort of 4,416 one-year survivors of a breast cancer. The role of the menopausal status and of the initial treatment modalities (surgery, radiotherapy, and chemotherapy) was investigated. Results.Excluding second primary breast cancer and non-melanoma skin cancer, a total of 193 (4.4%) patients developed a SMN between 1973 and 1992, compared with 136 expected (Standardised Incidence Ratio, SIR=1.4, 95% CI (1.2–1.6)). No trend towards either an increase or a decrease was noted in the SIR with time after treatment (p=0.2). The greatest increase in the relative risk concerned soft tissue cancers (SIR=13.0, 95% CI: 6.8–22.3), followed by leukaemia (SIR=3.1, 95% CI: 1.7–5.0), melanoma (SIR = 2.7, 95% CI: 1.4–4.8), kidney (SIR=2.5, 95% CI: 1.2–4.5), ovary (SIR=2.0, 95% CI: 1.2–3.1) and uterine tumours (SIR=1.9, 95% CI: 1.4–2.5). The SIR was 3.0 (95% CI 1.8–4.7) in women under 40 at the time of the breast cancer, 1.9 (95% CI : 1.4 – 2.4) in those aged 40–49 and 1.2 (95% CI 1.0–1.4) in those aged 50 or more. In the 2,514 women who had received radiotherapy as initial treatment without chemotherapy, the SIR for all SMN was 1.6 (95% CI: 1.1–2.3) fold higher than in those who had not received radiotherapy as initial treatment. Conclusion.In conclusion, this study confirms the increased risk of second malignancies in women treated for a breast cancer, and particularly in those who were younger at the time of treatment for breast cancer. Our results also suggest that radiotherapy may play a role in the onset of these second lesions.     

Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan

In a pooled analysis of two prospective studies with 35004 Japanese women, green-tea intake was not associated with a lower risk of breast cancer (222 cases), the multivariate relative risk for women drinking >or=5 cups compared with <1 cup per day being 0.84 (95% confidence interval 0.57-1.24, Trend P=0.69).     

Exposure to road traffic and railway noise and postmenopausal breast cancer: A cohort study

Exposure to traffic noise may result in stress and sleep disturbances. Studies on self‐reported sleep duration and breast cancer risk have found inconsistent results. In a population‐based Danish cohort of 29,875 women aged 50–64 years at enrolment in 1993–1997, we identified 1219 incident, postmenopausal breast cancer cases during follow‐up through 2010. Mean follow‐up time was 12.3 years. Road traffic and railway noise was calculated for all present and historical residential addresses from 1987 to 2010. We used Cox proportional hazard model for analyses and adjusted for hormone replacement therapy use, parity, alcohol consumption and other potential confounders. We found no overall association between residential road traffic or railway noise and breast cancer risk. Among women with estrogen receptor negative breast cancer, a 10‐dB higher level of road traffic noise (continuous scale) during the previous 1, 5 and 10 years were associated with 28% (95% CI: 1.04–1.56), 23% (95% CI: 1.00–1.51) and 20% (95% CI: 0.97–1.48) higher risks of estrogen receptor negative breast cancer, respectively, in fully adjusted models. Similarly, a 10‐dB increase in railway noise (1‐year mean at diagnosis address) increased risk for estrogen receptor negative breast cancer by 38% (95% CI: 1.01–1.89). There was no association between road traffic or railway noise and estrogen receptor positive breast cancer. In conclusion, these results suggest that residential road traffic and railway noise may increase risk of estrogen receptor negative breast cancer. As the first study on traffic noise and breast cancer results should be treated with caution.     

A nationwide epidemiologic study of breast cancer incidence following breast reduction surgery in a large cohort of Swedish women

Summary While it has been demonstrated that prophylactic mastectomy reduces breast cancer incidence among women at high risk, many women often consider this disfiguring surgery unacceptable. One alternative approach may be breast reduction surgery. In order to evaluate the long-term incidence of breast cancer following surgical removal of breast tissue, we have extended by 9 years the follow-up period of our earlier retrospective cohort study of Swedish women electing cosmetic breast reduction surgery (n=30,444) between 1965 and 1993, yielding an average of nearly 16 years of follow-up. Cancer incidence through 2002 was ascertained via the Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated comparing women who underwent breast reduction surgery with women in the general Swedish population. Breast cancer was observed in 443 women versus 624 expected for a statistically significant reduced SIR of 0.71 (95% CI=0.65–0.78). Analyses by age at surgery, time since surgery or calendar year of surgery revealed similar reductions in risk. Our study of over 30,000 women with long-term follow-up offers further evidence that women undergoing breast reduction surgery have reduced breast cancer risk. As the evidence from large-scale cohort studies accumulates, direct testing of this reduction in risk through clinical trials should be considered.     

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.