Long-term overweight and weight gain in early adulthood in association with risk of endometrial cancer

Long-term overweight and substantial weight gain over adulthood are known risk factors of endometrial cancer, but the timing of weight gain in relation to risk and the effect of weight change on age at diagnosis remain unclear. A population-based case-control study was conducted to evaluate the long-term effect of body weight on endometrial cancer risk. The study enrolled 668 incident cases and 674 population controls. Anthropometric features in each decade of adult life were ascertained through in-person interview and analyzed for their associations with endometrial cancer using unconditional logistic regression. As expected, high body mass index (BMI) was significantly associated with increased risk. Women who were overweight or obese at the time of interview had adjusted odds ratios of 1.54 (95%CI 1.13-2.10) and 4.76 (95%CI 3.50-6.49), respectively, compared to women of normal weight. Similar associations were observed for BMI assessed at each decade of adult life. More importantly, women who were overweight (BMI ≥ 25) in their 20s or 30s and maintained the overweight throughout life had significantly higher risk than those who became overweight at ages 40s or 50s. Women with substantial weight gain (≥35%) in early adulthood (age 20s) developed the disease 10 years earlier than those without such weight change in early life. These observations further confirm the critical link between body weight and development of endometrial cancer.     

Anthropometry, physical activity, and endometrial cancer risk: results from the Netherlands Cohort Study

Although obesity is an established risk factor for endometrial cancer, evidence linking risk to height, weight change since age 20, and physical activity is limited. In this case-cohort study, 62 573 women from The Netherlands Cohort Study on Diet and Cancer were followed up from 1986 to 1995, and 226 endometrial cancer case patients were identified. In Cox proportional hazards analyses, women 175 cm or taller had an increased risk of endometrial cancer compared with those less than 160 cm (rate ratio [RR] = 2.57, 95% confidence interval [CI] = 1.32 to 4.99). Compared with women with a body mass index (BMI; kg/m2) between 20 and 22.9, women with a BMI of 30 or greater had a higher risk (RR = 4.50, 95% CI = 2.62 to 7.72; P(trend)<.001). Moreover, BMI at age 20 and BMI gain since age 20 were positively associated with endometrial cancer risk (P(trend) = .02 and <.001, respectively). Women who spent 90 minutes per day or more doing nonoccupational physical activities had a lower risk (RR = 0.54, 95% CI = 0.34 to 0.85; P(trend) = .002) compared with those who spent less than 30 minutes per day. High BMI and low physical activity were strong and independent risk factors for endometrial cancer.     

Body weight in early adulthood,adult weight gain,and risk of endometrial cancer in women not using postmenopausal hormones

Purpose

High body mass index (BMI) measured in middle age or later is an established risk factor for endometrial cancer. However, whether BMI measured in early adulthood and adult weight change are associated with endometrial cancer risk is less clear, particularly among nonusers of postmenopausal hormones (PMH).

Methods

These associations were investigated among women in the Cancer Prevention Study II Nutrition Cohort. Women taking PMH (n = 11,624, 12 % of all women) were excluded, and the analysis was limited to 33,057 postmenopausal women who did not take PMH. Between enrollment in 1992/1993 and 30 June 2009, 447 women were diagnosed with endometrial cancer. Cox proportional hazards regression was used to calculate hazard rate ratios (RR) and corresponding 95 % confidence intervals (CI) for the association of BMI at age 18, calculated from recalled weight, and weight change between age 18 and 1992, with endometrial cancer incidence.

Results

BMI at age 18 was associated with higher risk of endometrial cancer in multivariable models adjusted for other risk factors (RR 1.29, 95 % CI 1.12–1.49 per 5 BMI units). Similarly, adult weight change was associated with higher risk of endometrial cancer (RR 1.81, 95 % CI 1.66–1.98 per 5 BMI unit change) in multivariable models adjusted for other risk factors.

Conclusions

High BMI at age 18 and greater adult weight gain were strongly associated with risk of endometrial cancer. These results underscore the importance of both avoiding overweight/obesity in young adulthood and preventing weight gain thereafter to minimize risk of this cancer.     

Prospective study of body size throughout the life‐course and the incidence of endometrial cancer among premenopausal and postmenopausal women

Although adult obesity is known to increase endometrial cancer risk, evidence for childhood obesity is limited. We prospectively examined the association between body fatness throughout life and endometrial cancer risk. 47,289 participants in the Nurses' Health Study (NHS) and 105,386 of the Nurses' Health Study II (NHS II) recalled their body fatness at ages 5, 10 and 20 using a pictogram. Childhood and adolescent body fatness were derived as the average at ages 5 and 10 and ages 10 and 20, respectively. We obtained adult weight from concurrent questionnaires. We calculated hazard ratios (HR) of endometrial cancer using Cox proportional hazards models. During follow‐up, 757 incident cases of endometrial cancer were diagnosed. Body fatness in childhood, at age 10, in adolescence and at age 20 were positively associated with endometrial cancer risk (HR for ≥ Level 5 versus ≤ Level 2 in adolescence: 1.83 (95% CI 1.41–2.37). After adjusting for most recent BMI, none of the associations persisted. Weight change since age 18 was positively associated with endometrial cancer risk [HR for ≥ 25 kg gain versus stable: 2.54 (95% CI 1.80–3.59). Adult BMI was strongly associated with endometrial cancer risk [HR BMI ≥ 35 kg/m² versus BMI ≤ 25 kg/m²: 4.13 (95% CI 3.29–5.16)]. In postmenopausal women, the association with BMI was significantly stronger among non‐users of hormone therapy. In conclusion, obesity throughout life is positively associated with endometrial cancer risk, with adult obesity one of the strongest risk factors. Maintaining a healthy weight throughout life remains important.     

Obesity,weight gain,and ovarian cancer risk in African American women

Although there is growing evidence that higher adiposity increases ovarian cancer risk, little is known about its impact in African American (AA) women, the racial/ethnic group with the highest prevalence of obesity. We evaluated the impact of body mass index (BMI) 1 year before diagnosis and weight gain since age 18 years on ovarian cancer risk in a population‐based case‐control study in AA women in 11 geographical areas in the US. Cases (n = 492) and age and site matched controls (n = 696) were identified through rapid case ascertainment and random‐digit‐dialing, respectively. Information was collected on demographic and lifestyle factors, including self‐reported height, weight at age 18 and weight 1 year before diagnosis/interview. Multivariable logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential covariates. Obese women had elevated ovarian cancer risk, particularly for BMI ≥ 40 kg/m² compared to BMI <25 (OR = 1.72, 95% CI: 1.12‐2.66; p for trend: 0.03). There was also a strong association with weight gain since age 18 (OR: 1.52; 95% CI: 1.07–2.16; p for trend: 0.02) comparing the highest to lowest quartile. In stratified analyses by menopausal status, the association with BMI and weight gain was limited to postmenopausal women, with a 15% (95% CI: 1.05–1.23) increase in risk per 5 kg/m² of BMI and 6% (95% CI: 1.01–1.10) increase in risk per 5 kg of weight gain. Excluding hormone therapy users essentially did not change results. Obesity and excessive adult weight gain may increase ovarian cancer risk in post‐menopausal AA women.     

Racial/ethnic differences in anthropometric and hormone-related factors and endometrial cancer risk: the Multiethnic Cohort Study

Background Anthropometric and hormone-related factors are established endometrial cancer risk factors; however, little is known about the impact of these factors on endometrial cancer risk in non-White women.Methods Among 110,712 women participating in the Multiethnic Cohort (MEC) Study, 1150 incident invasive endometrial cancers were diagnosed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with endometrial cancer risk for race/ethnicity and for risk factors across racial/ethnic groups were calculated.Results Having a higher body mass index (BMI) at baseline or age 21 years was strongly associated with increased risk (p_int race/ethnicity ≥ 0.36). Parity (vs nulliparity) was inversely associated with risk in all the groups except African Americans (p_int 0.006). Current use of postmenopausal hormones at baseline (PMH-E; vs never use) was associated with increased risk in Whites and Japanese Americans (p_int 0.002). Relative to Whites, endometrial cancer risk was lower in Japanese Americans and Latinas and non-significantly higher in Native Hawaiians. Risk in African Americans did not differ from that in Whites.Conclusions Racial/ethnic differences in endometrial cancer risk were not fully explained by anthropometric or hormone-related risk factors. Further studies are needed to identify reasons for the observed racial/ethnic differences in endometrial cancer risk.Subject terms: Cancer epidemiology, Endometrial cancer, Risk factors     

Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study

We examined the relationship of body mass index (BMI), diabetes and smoking to endometrial cancer risk in a cohort of 36 761 Norwegian women during 15.7 years of follow-up. In multivariable analyses of 222 incident cases of endometrial cancer, identified by linkage to the Norwegian Cancer Registry, there was a strong increase in risk with increasing BMI (P-trend <0.001). Compared to the reference (BMI 20-24 kg m(-2)), the adjusted relative risk (RR) was 0.53 (95% confidence interval (CI): 0.19-1.47) for BMI<20 kg m(-2), 4.28 (95% CI: 2.58-7.09) for BMI of 35-39 kg m(-2) and 6.36 (95% CI: 3.08-13.16) for BMI>or=40 kg m(-2). Women with known diabetes at baseline were at three-fold higher risk (RR 3.13, 95% CI: 1.92-5.11) than those without diabetes; women who reported current smoking at baseline were at reduced risk compared to never smokers (RR 0.55, 95% CI: 0.35-0.86). The strong linear positive association of BMI with endometrial cancer risk and a strongly increased risk among women with diabetes suggest that any increase in body mass in the female population will increase endometrial cancer incidence.     

Prospective cohort study of general and central obesity,weight change trajectory and risk of major cancers among Chinese women

General obesity, typically measured using body mass index (BMI), has been associated with an increased risk of several cancers. However, few prospective studies have been conducted in Asian populations. Although central obesity, often measured using waist–hip ratio (WHR), is more predictive for type 2 diabetes and cardiovascular diseases (CVD) risk than BMI, knowledge of its association with cancer incidence is limited. In a cohort of 68,253 eligible Chinese women, we prospectively investigated the association of BMI, WHR and weight change during adulthood with risk of overall cancer and major site‐specific cancers using multivariate Cox proportional hazard models. Compared to the BMI group of 18.5–22.9 kg/m², obese (BMI ≥ 30 kg/m²) women were at an increased risk of developing overall cancer (hazard ratio = 1.36, 95% confidence interval = 1.21–1.52), postmenopausal breast cancer (HR: 2.43, 95% CI: 1.73–3.40), endometrial cancer (HR: 5.34, 95% CI: 3.48–8.18), liver cancer (HR: 1.93, 95% CI: 1.14–3.27) and epithelial ovarian cancer (HR: 2.44, 95% CI: 1.37–4.35). Weight gain during adulthood (per 5 kg gain) was associated with increased risk of all cancers combined (HR: 1.05, 95% CI: 1.03–1.08), postmenopausal breast cancer (HR: 1.17, 95% CI: 1.10–1.24) and endometrial cancer (HR: 1.37, 95% CI: 1.27–1.48). On the other hand, WHR was not associated with cancer risk after adjustment for baseline BMI. These findings suggest that obesity may be associated with cancer risk through different mechanisms from those for type 2 diabetes and CVD and support measures of maintaining health body weight to reduce cancer risk in Chinese women.     

Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer

AimObesity is an established risk factor for endometrial cancer. Associations tend to be stronger for the endometrioid subtype. The role of adult weight change and weight cycling is uncertain. Our study aimed to determine whether there is an association between different adult weight trajectories, weight cycling and risk of endometrial cancer overall, and by subtype.MethodsWe analysed data from the Australian National Endometrial Cancer study, a population-based case–control study that collected self-reported information on height, weight at three time points (age 20, maximum and 1 year prior to diagnosis [recent]), intentional weight loss/regain (weight cycling) from 1398 women with endometrial cancer and 1538 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis.ResultsRelative to women who maintained a stable weight during adulthood, greater weight gain after the age of 20 was associated with increased risk of endometrial cancer (OR for gain 40+kg all subtypes 5.3, 95% CI 3.9–7.3; endometrioid 6.5, 95% CI 4.7–9.0). The strongest associations were observed among women who were continually overweight from the age of 20 (all subtypes OR 3.6, 95% CI 2.6–5.0). Weight cycling was associated with increased risk, particularly among women who had ever been obese (OR 2.9 95% CI 1.8–4.7), with ～3-fold risks seen for both endometrioid and non-endometrioid tumour subtypes. Women who had intentionally lost weight and maintained that weight loss were not at increased risk.ConclusionThese results suggest that higher adult weight gain, and perhaps weight cycling, independently increase the risk of endometrial cancer, however women who lost weight and kept that weight off were not at increased risk.     

Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden)

Objective: To measure the association between endometrial cancer risk and obesity at age 18 and recently, adult weight gain, diabetes mellitus and hypertension. Methods: We performed a population-based, nationwide case–control study among postmenopausal women aged 50–74 years in Sweden, including 709 incident cases with histopathologically verified endometrial cancer and 3368 controls. Results: Compared to lean women (recent body mass index (BMI), i.e. kg/m² below 22.5), overweight women (recent BMI 28–29.99) had a 50% increase in risk for endometrial cancer (OR 1.5, 95% CI 1.0–2.1). Obese women (recent BMI 30–33.99) had a 3-fold increased risk (OR 2.9, 95% CI 2.0–4.0), and markedly obese women (recent BMI 34) a 6-fold increased risk (OR 6.3, 95% CI 4.2–9.5). The OR for Type 2 diabetes mellitus was 1.5 (95% CI 1.0–2.1) and for Type 1 diabetes mellitus it was 13.3 (3.1–56.4). The effect of recent BMI was similar for tumors having different degrees of differentiation and myometrial invasion, and did not vary with age, time since menopause, smoking status, diabetes mellitus, and use of contraceptives. Hypertension increased risk only among obese women. BMI at age 18, height, and adult weight change were not independent risk factors. Conclusions: Recent overweight/obesity and diabetes mellitus (Types 1 and 2) are associated with endometrial cancer risk. Hypertension increases risk among obese women.     

Night shift work and the risk of endometrial cancer

Melatonin has several oncostatic properties, including possible anti-estrogenic and anti-aromatase activity, and seems to be linked with fat metabolism. Night workers have lower levels of melatonin, which may predispose them to develop cancer. Endometrial cancer risk is influenced significantly by hormonal and metabolic factors; therefore, we hypothesize that night workers may have an increased risk of endometrial cancer. Of the 121,701 women enrolled in a prospective cohort study, 53,487 women provided data on rotating night shift work in 1988 and were followed through on June 1, 2004. A total of 515 women developed medical record-confirmed invasive endometrial cancer. We used Cox regression models to calculate multivariate relative risks (MVRRs), controlling for endometrial cancer risk factors. Women who worked 20+ years of rotating night shifts had a significantly increased risk of endometrial cancer [MVRR, 1.47; 95% confidence interval (95% CI), 1.03-1.14]. In stratified analyses, obese women working rotating night shifts doubled their baseline risk of endometrial cancer (MVRR, 2.09; 95% CI, 1.24-3.52) compared with obese women who did no night work, whereas a nonsignificant increase was seen among non-obese women (MVRR, 1.07; 95% CI, 0.60-1.92). Women working rotating night shifts for a long duration have a significantly increased risk of endometrial cancer, particularly if they are obese. We speculate that this increased risk is attributable to the effects of melatonin on hormonal and metabolic factors. Our results add to growing literature that suggests women who work at night may benefit from cancer prevention strategies.     

Migraine History, Nonsteroidal Anti-inflammatory Drug Use, and Risk of Postmenopausal Endometrial Cancer

Endometrial cancer is primarily a hormonally mediated disease. As such, factors that mediate or reflect exposure to estrogens, or that mediate response to such exposure, may plausibly be associated with endometrial cancer risk. History of migraines, another hormonally mediated condition, has recently been associated with a reduced risk of hormone receptor-positive breast cancer; however, the relationship between migraines and endometrial cancer has not previously been explored. We evaluated the relationship between migraine history and endometrial cancer risk in postmenopausal women, considering also the potential impact of nonsteroidal anti-inflammatory drug (NSAID) use, given the relationship of NSAIDs to hormones and to migraine history. We identified 93,384 women participating in the Women??s Health Initiative prospective cohort who had an intact uterus at the time of study entry. Using Cox proportional hazards regression, we assessed risk of endometrial cancer during study follow-up according to history of migraines and according to current NSAID use at the time of study entry, adjusting for age, study arm, race, and hormone therapy use. We also evaluated interaction in these associations by body mass index. Having a history of migraines was not associated with endometrial cancer risk [hazard ratio (HR)?=?0.91, 95?% confidence interval (CI)?=?0.75?C1.11], regardless of body mass index (BMI) or NSAID use status. Similarly, current NSAID use was not associated with endometrial cancer risk (HR?=?1.01, 95?% CI?=?0.88?C1.16), regardless of BMI. Migraine history and NSAID use do not appear to be associated with risk of endometrial cancer.     

Racial/ethnic differences in colorectal cancer risk: the multiethnic cohort study

Incidence rates in the United States show clear racial/ethnic disparities for colorectal cancer. We examined the extent to which ethnic differences in risk factors could explain the age-adjusted variation in the risk of colorectal cancer, overall and by stage at diagnosis, among 165,711 African Americans, Japanese Americans, Latinos, Native Hawaiians and whites participating in the Multiethnic Cohort Study. Over a median follow-up period of 10.7 years, 2,564 incident cases of colorectal cancer were identified through surveillance, epidemiology and end result tumor registry linkages in Hawaii and California. Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for each ethnic group compared to whites. After accounting for known/suspected risk factors, Japanese Americans (men, RR = 1.27, 95% CI = 1.09-1.48; women, RR = 1.49, 95% CI = 1.24-1.78) and African American women (RR = 1.48, 95% CI = 1.23-1.79) remained at increased risk of colorectal cancer relative to whites; African American and Japanese American women were also at increased risk of advanced disease compared to whites. In site-specific analyses, after multivariable adjustment, African Americans (both sexes) and Japanese American women remained at increased risk for colon cancer, and Japanese Americans (both sexes) and Native Hawaiian men for rectal cancer compared to whites. The results of our study suggest that differences in the distribution of known/suspected risk factors account for only a modest proportion of the ethnic variation in colorectal cancer risk and that other factors, possibly including genetic susceptibility, are important contributors to the observed disparities in incidence.     

Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition

Objective To examine the association between anthropometry and endometrial cancer, particularly by menopausal status and exogenous hormone use subgroups. Methods Among 223,008 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during 6.4 years of follow-up. The analysis was performed with Cox proportional hazards modeling. Results Weight, body mass index (BMI), waist and hip circumferences and waist–hip ratio (WHR) were strongly associated with increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30– < 40 kg/m²) compared to normal weight (BMI < 25) women was 1.78, 95% CI = 1.41–2.26, and for morbidly obese women (BMI ≥ 40) was 3.02, 95% CI = 1.66–5.52. The RR for women with a waist circumference of ≥88 cm vs. <80 cm was 1.76, 95% CI = 1.42–2.19. Adult weight gain of ≥20 kg compared with stable weight (±3 kg) increased risk independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11–2.77). These associations were generally stronger for postmenopausal than premenopausal women, and oral contraceptives never-users than ever-users, and much stronger among never-users of hormone replacement therapy compared to ever-users. Conclusion Obesity, abdominal adiposity, and adult weight gain were strongly associated with endometrial cancer risk. These associations were particularly evident among never-users of hormone replacement therapy.     

Aspirin, NSAID, and acetaminophen use and the risk of endometrial cancer

To date, no prospective studies have explored the relationship between the use of aspirin, other nonsteroidal anti-inflammatory medications (NSAID), and acetaminophen and endometrial adenocarcinoma. Of the 82,971 women enrolled in a prospective cohort study, 747 developed medical record-confirmed invasive endometrial cancer over a 24-year period. Use of aspirin was ascertained from 1980 to 2004, and for other NSAIDs and acetaminophen, from 1990 to 2004. Cox regression models calculated multivariate relative risks (MV RR), controlling for body mass index (BMI), postmenopausal hormone (PMH) use, and other endometrial cancer risk factors. Currency, duration, and quantity of aspirin were not associated with endometrial cancer risk overall [current use: MV RR, 1.03; 95% confidence interval (CI) 0.83-1.27; >10 years of use: MV RR, 1.01; 95% CI, 0.78-1.30; and cumulative average >7 tablets per week: (MV RR, 1.10; 95% CI, 0.84-1.44)]. However, stratified analyses showed that a lower risk of endometrial cancer among obese (BMI, >or=30 kg/m(2)) women was seen with current aspirin use (MV RR, 0.66; 95% CI, 0.46-0.95). The greatest risk reduction for current aspirin users was seen in postmenopausal obese women who had never used PMH (MV RR, 0.43; 95% CI, 0.26-0.73). The use of other NSAIDs or acetaminophen was not associated with endometrial cancer. Our data suggest that use of aspirin or other NSAIDs does not play an important role in endometrial cancer risk overall. However, risk was significantly lower for current aspirin users who were obese or who were postmenopausal and had never used PMHs; these subgroup findings require further confirmation.     

Association of gain and loss of weight before and after menopause with risk of postmenopausal breast cancer in the Iowa women's health study.

Obesity and adult weight gain are well-established risk factors for postmenopausal breast cancer. Although there are a few studies demonstrating the contribution of adult weight gain to breast cancer risk, whether weight gain during a critical time period is specifically associated with risk, or whether subsequent weight loss among women who have gained weight will reduce the excess risk, is not firmly established. We investigated the association of changes in weight (loss or gain in excess of 5% of body weight) using two risk factor models: (a) age 18 to 30 years and age 30 years to menopause and (b) age 30 years to menopause and after the menopause to the baseline study in 1986 on risk of postmenopausal breast cancer in a prospective cohort of 33,660 postmenopausal women in Iowa. Over 15 years of follow-up, 1,987 cases of breast cancer occurred. Data were analyzed using proportional hazards regression models adjusted for established breast cancer risk factors. The most frequently observed pattern of body weight over time was a consistent increase; these women were observed to have the highest rates of breast cancer and served as the reference category for all comparisons. The lowest-risk groups were (a) women who maintained or lost weight from age 18 to 30 years and then lost weight from age 30 years to menopause [risk ratio (RR), 0.36; 95% confidence interval (95% CI), 0.22-0.60] and (b) women who maintained or lost weight from age 30 years to menopause and then lost weight after the menopause (RR, 0.48; 95% CI, 0.22-0.65). Women who gained weight from age 30 years to menopause but then lost weight after the menopause experienced risk reductions (RR, 0.77; 95% CI, 0.64-0.92) although perhaps slightly smaller in magnitude than women who maintained their weight in both time intervals (RR, 0.63; 95% CI, 0.55-0.73). Women who gained weight from age 18 to 30 years and then lost weight from age 30 years to menopause had comparable risk reductions (RR, 0.61; 95% CI, 0.46-0.8) with women who maintained their weight in both time intervals (RR, 0.73; 95% CI, 0.64-0.84). Women who gained weight during the period from age 30 years to menopause but who had stable weight after menopause had rates similar to the reference group. These data suggest prevention of weight gain between age 18 years and menopause or weight loss and maintenance during these years reduces risk of postmenopausal breast cancer.     

Body size and breast cancer risk: the Multiethnic Cohort

The influence of body size on postmenopausal breast cancer risk was investigated among five racial/ethnic groups in the Multiethnic Cohort. Participants were 45-75 years old at recruitment (1993-1996), living in Hawaii and California. Of the 82,971 White, African American, Native Hawaiian, Japanese and Latina women included in this analysis, 3,030 were diagnosed with invasive breast cancer. Body mass index (BMI), height, weight and adulthood weight gain were associated with a significantly higher risk and, with the exception of height, were found to vary across ethnic groups. Native Hawaiians and Japanese with a BMI≥30.0 compared to 20.0-24.9 kg/m2 had the highest risk (hazard ratio=1.82, 95% confidence interval: 1.31, 2.54, p-trend=0.001, and hazard ratio=1.59, 95% confidence interval: 1.24, 2.05, p-trend<0.0001, respectively). Current hormone replacement therapy use modified the impact of a high BMI, as non- and former users had a significantly higher risk compared to current users. BMI also had a more pronounced risk for advanced tumors compared to localized tumors. When both BMI and adult weight gain were analyzed simultaneously, adult weight gain, rather than BMI, was a significant risk factor overall. These findings emphasize the significance of maintaining a healthy weight throughout adulthood for the prevention of postmenopausal breast cancer.     

Reproductive history,breast‐feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study

Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population‐based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast‐feeding. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two‐fold for parous women who never breast‐fed compared to nulliparous women (OR = 2.02, 95% CI = 1.12–3.63). For younger parous women, longer duration of lifetime breast‐feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR = 0.52, 95% CI = 0.26–1.04, P_trend = 0.06). Considering the joint effect of parity and breast‐feeding, risk was increased two‐fold for women with ≥3 full‐term pregnancies (FTPs) and no or short‐term (<12 months) breast‐feeding compared to women with 1–2 FTPs and breast‐feeding ≥12 months (OR = 2.56, 95% CI = 1.22–5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short‐term breast‐feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%) and non‐Hispanic whites (6%). Breast‐feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of FTPs in women under age 50 years.     

Tamoxifen therapy for breast cancer and endometrial cancer risk.

BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.     

Carbohydrate intake, glycemic index and glycemic load in relation to risk of endometrial cancer: A prospective study of Swedish women

The associations of carbohydrate intake, glycemic index and glycemic load with endometrial cancer risk were examined among 61,226 participants of the Swedish Mammography Cohort who were cancer-free at enrollment between 1987 and 1990 and completed a food frequency questionnaire. During a mean follow-up of 15.6 years, through June 2005, 608 incident cases of endometrial adenocarcinoma were diagnosed. We observed no overall association between carbohydrate intake, glycemic index or glycemic load and incidence of endometrial cancer; the rate ratios (RRs) for the highest versus the lowest quintile were 1.12 (95% CI, 0.85-1.47) for carbohydrate intake, 1.00 (95% CI, 0.77-1.30) for glycemic index and 1.15 (95% CI, 0.88-1.51) for glycemic load. However, among obese women (body mass index, BMI > or =30 kg/m2), endometrial cancer incidence was nonsignificantly elevated in the top versus bottom quintiles of carbohydrate intake (RR, 1.68; 95% CI, 0.86-3.29) and glycemic load (RR, 1.57; 95% CI, 0.82-2.99). In a subanalysis of women who completed a follow-up questionnaire in 1997, which collected information on physical activity, carbohydrate intake and glycemic load were positively related to endometrial cancer risk among overweight women (BMI > or =25 kg/m2) with low physical activity. In this subgroup, the multivariate RRs comparing extreme quartiles were 1.90 (95% CI, 0.84-4.31) for carbohydrate intake and 2.99 (95% CI, 1.17-7.67) for glycemic load. Results from this cohort study suggest that a high carbohydrate intake and a high glycemic load may increase the risk of endometrial cancer among overweight women with low physical activity.