Exogenous hormone use and the risk of postmenopausal breast cancer: results from the Netherlands Cohort Study

The association between the use of exogenous hormones as either oral contraceptives (OC) or hormone replacement therapy (HRT) in relation to postmenopausal breast cancer incidence was examined in the Netherlands Cohort Study (NLCS) among 62,573 women aged 55 to 69 years. Information on these types of exogenous hormone use and other risk factors was collected by mailed questionnaire. During 3.3 years of follow-up, 471 incident breast cancer cases were identified. After adjustment for traditional breast cancer risk factors, the relative risk (RR) of breast cancer was 1.09 (95 percent confidence interval [CI]=0.79–1.48) for women who ever used OCs cf women who never used OCs. The relative rates (with CIs) for women who used OCs for a period < 5 years, 5–9 years, 10–14 years, and 15+ years were 0.97 (0.61–1.55), 1.20 (0.69–2.07), 1.03 (0.60–1.77), and 1.96 (0.99–3.89), respectively. The test for trend was not significant (P=0.13). There was no evidence of any association between the number of years between the first and the last use of OCs and breast cancer incidence. In the subgroup of women with first-degree relatives with breast cancer, the RR for breast cancer associated with ever use of OCs was 1.51 (CI=0.67–3.41), whereas in the remaining women, the RR was 0.97 (CI=0.73–1.27). Ever-use of HRT compared with never-use was not associated with an increase in breast cancer risk in the multivariate analysis (RR=0.99, CI=0.68–1.43). Also, the number of years of HRT use was not associated with an increased breast cancer risk (trend P=0.83), nor was the number of years between the first and the last use of HRT and breast cancer incidence. One subgroup of women in which the use of HRT seemed associated (but not significantly) with an increase in breast cancer risk was women with an induced menopause (RR=1.72, CI=0.95–3.12). The RR of breast cancer for women who had ever used both OCs and HRT, compared with women who never used these exogenous hormones was 1.00 (CI=0.51–1.94). From this study, it cannot be concluded that the use of exogenous hormones is a strong risk factor for the development of postmenopausal breast cancer.Since the acceptance of this paper, two other papers have been published on HRT and breast cancer. For HRT (estrogen alone), one supports our finding of no association (Stanford et al, JAMA 1995; 274: 137–42) and one did find a positive association for current use (Colditz et al, New Engl J Med 1995; 332: 1589–93), most pronounced in older women with longer durations of use. With regard to use of combined estrogen-progestin HRT, the results in both papers were comparable to those for estrogen alone. More research on (combinations of) types of hormones is needed.This work was supported by the Dutch Cancer Society.     

Reproductive factors,exogenous female hormone use and breast cancer risk in Japanese: the Miyagi Cohort Study

The incidence of breast cancer among Japanese women is substantially increasing. This population-based prospective cohort study in Japan evaluated the associations of reproductive factors and exogenous female hormone use with breast cancer risk, both overall and separately among premenopausal and postmenopausal women. A total of 24,064 women aged 40–64 were followed from 1990 to 2003. During 309,424 person-years of follow-up, 285 breast cancer cases were documented. In overall evaluation, nulliparity was significantly associated with an increased risk of breast cancer. There was a significant decrease in risk with increasing parity number among parous women (trend P = 0.008). No association was observed between age at menarche or age at first birth and breast cancer risk. Neither oral contraceptive (OC) use nor the use of exogenous female hormones other than OC was associated with breast cancer risk. The evaluation according to menopausal status revealed that nulliparity and parity number were significantly related to breast cancer risk only among postmenopausal women. Later age at natural menopause was associated with an increased risk of breast cancer among postmenopausal women (trend P = 0.02). Our findings suggest that parity number and age at menopause have great effects on breast cancer risk among Japanese women.     

Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

OBJECTIVE: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. METHODS: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case-control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. RESULTS: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01-1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97-1.03). CONCLUSIONS: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.     

Hormone replacement therapy and breast cancer in former users of oral contraceptives--The Norwegian Women and Cancer study

Combined estrogen-progestin menopausal therapy (HRT) and combined estrogen-progestin contraceptives (OC) both increase breast cancer risk during current use and a few years after. We investigated risk of breast cancer in women who were users of HRT dependant on former history of OC use in a large, national population-based cohort study, the Norwegian Women and Cancer study (NOWAC). Exposure information was collected through postal questionnaires. Based on follow-up of 30,118 postmenopausal women by linkage to national registers of cancer, deaths, and emigration we revealed 540 incident breast cancer cases between 1996 and 2004. Compared to never users of either drugs current use of HRT gave a significant (p = 0.002) higher risk of breast cancer in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for estrogen only and combinations with progestin added in ever users of OCs. The increased risk of breast cancer in current HRT users with a history of former OC use could have potential great impact on postmenopausal breast cancer risk as the proportion of postmenopausal women with former OC use will continue to increase.     

Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh-day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow-up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12-2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00-1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71-2.85).     

Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer

Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan? allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p<0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47T>C and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.     

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

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

Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States)

Objective: The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. Methods: Using data from an incident population-based case (n = 1972) and control (n = 2386) study of colon cancer we evaluated if estrogen modifies the association between BMI and risk of colon cancer. Results: Women who were estrogen-negative (postmenopausal women not taking hormone replacement therapy, HRT) were at increased risk of colon cancer regardless of indicator of estrogen status used (i.e. estrogen-negative compared to estrogen-positive women defined as either being premenopausal or postmenopausal women using HRT, OR 1.54, 95% CI 1.23–1.93; no recent exposure to estrogens compared to current or HRT use within the past 2 years, OR 1.58, 95% CI 1.24–2.00; postmenopausal women not currently using HRT compared to postmenopausal women taking HRT, OR 1.65, 95% CI 1.29–2.12). BMI (kg/m²) was not associated with an increased risk of colon cancer among women who were estrogen-negative. However, women who were estrogen-positive experienced a greater than two-fold increase in colon cancer risk if they had a BMI of > 30 relative to those who had a BMI of <23 (for estrogen-positive, OR, 2.50, 95% CI 1.51–4.13; premenopausal, OR 2.19, 95% CI 0.94–5.07; postmenopausal using HRT, OR 3.36, 95% CI 1.58–7.13). Among men the colon cancer risk associated with BMI decreased with advancing age. Physical activity modified the increased colon cancer risk associated with a large BMI. Conclusions: These data suggest the importance of estrogen in colon cancer etiology. Being estrogen-negative resulted in a significant increased risk of colon cancer. However, BMI significantly increased the risk of colon cancer among women who were estrogen-positive. We hypothesize that estrogen up-regulates IGF-I receptors and IRS-I levels in the colon, which in turn increases susceptibility to obesity-induced increased levels of insulin. We further hypothesize that androgens may have similar effects in men given the decline in colon cancer risk associated with BMI with advancing age.     

Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project

The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women.     

Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study.

Excess adiposity and hormone replacement therapy (HRT) are important contributors to postmenopausal breast cancer risk. HRT has been shown to modify the association between body weight and breast cancer risk, although few studies are sufficiently large to examine the risk of breast cancer associated with body mass index (BMI) and weight gain separately among current HRT users and nonusers. This study includes 1,934 incident breast cancer cases occurring among 62,756 postmenopausal women in the Cancer Prevention Study-II Nutrition Cohort. Age-adjusted incidence rates were calculated, and Cox proportional hazards models were used to examine the association of BMI and adult weight gain (since age 18 years) with breast cancer risk stratified by HRT use. Total adult weight gain strongly predicted breast cancer risk among former and never HRT users (P for trend < 0.0001). Weight gain of 21-30 pounds was associated with a rate ratio of 1.4 (95% confidence interval 1.1-1.8); rates doubled among women gaining >70 pounds compared with women who maintained their weight within 5 pounds of their weight at age 18. After accounting for weight gain, neither recent BMI nor BMI at age 18 were independent predictors of risk. Among current HRT users, no association was seen between breast cancer and either BMI or weight gain. Adult weight gain is strongly associated with postmenopausal breast cancer only among non-HRT users in this study. These data illustrate the importance of examining breast cancer risk factors separately by HRT use; the effects of other risk factors may be attenuated or obscured among women taking HRT.     

Estrogen-progestin replacement therapy and breast cancer risk: the Women's Health Study (United States)

Objective: While there is substantial evidence that unopposed estrogen use increases the risk of breast cancer, there are limited data from epidemiologic studies on the impact of estrogen–progestin combinations. We therefore examined estrogen–progestin replacement therapy and breast cancer risk in the Women's Health Study. Methods: We investigated postmenopausal hormone (PMH) use among 17,835 apparently healthy postmenopausal women aged 45 years, and followed them prospectively for an average of 5.9 years. Breast cancer occurred in 411 women. Results: The multivariate relative risks of all breast cancer associated with never use of PMH, use of estrogen replacement therapy (ERT), and use of estrogen–progestin replacement therapy (HRT) were 1.00 (referent), 0.96 (95% CI 0.65–1.42), and 1.37 (95% CI 1.05–1.78). The increase in risk among users of HRT was largely limited to those women who had used estrogen–progestin replacement therapy for five years or more, and to those women who were on continuous rather than cyclic progestin combinations. Higher doses of estrogen, but not progestin, were associated with increased breast cancer risk, compared with lower doses. Conclusions: These prospective data suggest that use of estrogen–progestin replacement therapy imparts an increased risk of breast cancer in comparison with never use of PMH.     

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

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

A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden)

Objectives: Reports suggest that combined estrogen plus progestin hormone replacement therapy (HRT) confers a higher breast cancer risk than estrogen alone. We aimed to establish whether breast cancer risk depends on the type of HRT formula. Methods: The cohort consisted of 6586 women, aged 50–64 years, from the Lund area, Sweden, with no reported breast cancer upon inclusion. We obtained information such as HRT use through a questionnaire between December 1995 and February 2000. New breast cancers were identified through the South Swedish tumor registry. Results: Between inclusion and December 2001, 101 women developed breast cancer. Only ever use of the continuous combined estrogen plus progestin (CCEP) formula differed between cases and controls (45.2% versus 23.5%; p = 0.000001). Compared with never users, exclusive CCEP users had the highest age-adjusted hazard ratio HR 3.3 (95% CI: 1.9–5.6; p < 0.001), followed by users of CCEP in addition to other HRT formulas HR 2.8 (95% CI: 1.4–5.5; p = 0.003). No significant increase was seen in women who exclusively used other HRT formulas. Conclusion: Women who used CCEP had over three times the risk of developing breast cancer compared with never users and twice the risk compared with users of other types of HRT.     

Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO)

Background:

The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated.

Methods:

We performed a pooled analysis of six case–control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types.

Results:

A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68–0.97) and HRT ever users (OR=0.77; 95% CI: 0.66–0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61–0.94, and OR=0.66; 95% CI: 0.49–0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37–0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66–0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19–0.71) in HRT users. No interaction with smoking status or BMI was observed.

Conclusion:

Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women.     

Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US women

Due to its potential effects on ovarian hormone production, physical activity has been proposed as a modifiable risk factor for breast cancer. The authors analyzed data from the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort to examine the association between various measures of physical activity and postmenopausal breast cancer risk. Information on physical activity was obtained in 1992 via a self-administered questionnaire for 72,608 postmenopausal female participants who were cancer-free. During the five year prospective follow-up, 1520 incident breast cancer cases were identified among these women. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) and to adjust for potential confounding factors including mammography. Women who were most physically active (>42.0 MET-h/week) at baseline had 29% lower incidence rates than active women with the least activity (>0–7.0 MET-h/week) (95% CI, 0.49–1.02). The difference in risk was largest for localized breast cancer, and for women who did not use hormone replacement therapy (HRT) at enrollment. Our findings are consistent with other studies that show lower risk of postmenopausal breast cancer associated with regular physical activity.     

Passive and active smoking and breast cancer risk in Canada, 1994–97

Background: Studies comparing ever smokers with never smokers have found little increase in breast cancer risk. However, the five published studies examining passive smoking and breast cancer have all suggested associations with both passive and active smoking, particularly premenopausal risk. Methods: We analyzed data collected through the Canadian National Enhanced Cancer Surveillance System, from 805 premenopausal and 1512 postmenopausal women with newly diagnosed (incident), histologically confirmed, primary breast cancer and 2438 population controls. The mailed questionnaire included questions on breast cancer risk factors and a lifetime residential and occupational history of exposure to passive smoking. Results: Among premenopausal women who were never active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer odds ratio (OR) of 2.3 (95% confidence interval [CI] 1.2–4.6). Passive exposure showed a strong dose–response trend (test for trend p=0.0007) with an OR of 2.9 (95% CI 1.3–6.6) for more than 35 years of passive residential and/or occupational exposure. When premenopausal women who had ever actively smoked were compared with women never regularly exposed to passive or active smoke, the adjusted OR for breast cancer was also 2.3 (95% CI 1.2–4.5). Among postmenopausal women who were never-active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer OR of 1.2 (95% CI 0.8–1.8) and an OR of 1.4 (95% CI 0.9–2.3) for the most highly exposed quartile of women. The adjusted OR for postmenopausal breast cancer risk for ever-active smokers compared with women never regularly exposed to passive or active smoke was 1.5 (95% CI 1.0–2.3). Statistically significant dose–response relationships were observed with increasing years of smoking, increasing pack-years and decreasing years since quitting. Women with 35 or more years of smoking had an adjusted OR of 1.7 (95% CI 1.1–2.7). Conclusions: Active and passive smoking may be associated with increased breast cancer risk, particularly premenopausal risk.     

Intake of whole grain products and risk of breast cancer by hormone receptor status and histology among postmenopausal women

No clear relationship between whole grain products and risk of breast cancer has been established. In a large prospective cohort study, we investigated the association between intake of whole grain products and risk of breast cancer by tumour receptor status [oestrogen receptor (ER) and progesterone receptor (PR)] and tumour histology (ductal/lobular). It was further investigated whether the association differed by use of hormone replacement therapy (HRT). The study included 25,278 postmenopausal women participating in the Danish Diet, Cancer and Health cohort study (1993–1997). During a mean follow‐up time of 9.6 years, 978 breast cancer cases were diagnosed. Associations between intake of whole grain products and the breast cancer rate were analysed using Cox's regression model. A higher intake of whole grain products was not associated with a lower risk of breast cancer. Per an increment in intake of total whole grain products of 50 g per day the adjusted incidence rate ratio (95% confidence interval) was 1.01 (0.96–1.07). Intake of rye bread, oatmeal and whole grain bread was not associated with breast cancer risk. No association was observed between the intake of total or specific whole grain products and the risk of developing ER+, ER?, PR+, PR?, combined ER/PR status, ductal or lobular breast cancer. Furthermore, there was no interaction between intake of whole grain products and use of HRT on risk of breast cancer. In conclusion, intake of whole grain products was not associated with risk of breast cancer in a cohort of Danish postmenopausal women. © 2008 Wiley‐Liss, Inc.     

Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study

Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.     

Oral contraceptive use and breast cancer risk among African-American women

Recent epidemiologic studies, most of them in predominantly White populations, have suggested that long duration of oral contraceptive (OC) use may increase the risk of breast cancer at young ages. We assessed the relationship of OC use to the risk of breast cancer in African-American women aged 25 to 59 years, using interview data from a multipurpose hospital-based case-control study. Five hundred and twenty-four cases hospitalized for invasive breast cancer were compared with 1,021 controls with nonmalignant conditions unrelated to OC use. Relative risks (RR) and 95 percent confidence intervals (CI) were estimated relative to a reference category of use for less than 12 months; potential confounders were controlled by multiple logistic regression analysis. Among women under age 45, three or more years of OC use was associated with an increased risk of breast cancer: the RR estimate was 2.8 (CI=1.5–5.0) for three to four years of use, and declined to 1.5 (CI=0.8.3.0) for 10 or more years of use. Recency and timing of use did not explain the observed association. Among women aged 45 to 59, OC use was associated with little or no increase in risk: the RR estimate for three or more years of use was 1.3 (CI=0.7–2.4). The findings add to the evidence from studies of White women and a recent study of Black women which have suggested an increased risk of breast cancer at young ages for moderate or long duration use of OCs.This research was supported by the US National Cancer Institute (grants R01 CA55766 and R01 CA45762). Additional support was provided by the US Food and Drug Administration (FD-U-000082); the views expressed do not necessarily represent the views of the Food and Drug Administration. The Slone Epidemiology Unit also receives support from Hoffmann-La Roche, Inc., and Marion Merrell Dow Inc.