Breast Cancer Detection Demonstration Project Research Articles

Reply to ‘Sleep duration and breast cancer risk in the breast cancer detection demonstration project follow-up cohort: true associations or bias?’

Sir, We thank Yang et al (2015) for their interest in and thoughtful review of our study. We agree with the correspondents that certain limitations should be considered when interpreting findings on sleep duration and breast cancer risk. As we acknowledged in our paper, self-reported sleep duration involving measurement error could lead to misclassification of our main exposure. We agree with Yang et al that misclassification can lead to bias in either direction. However, in our case, we believe the bias is more likely to be towards the null. A validation study by Lauderdale et al (2008) compared self-reported sleep duration to an objective measure (actigraphy), and found that the validity of self-reported sleep varied by the amount of sleep recorded. In general people tended to over-report their sleep duration, but the extent of over-reporting increased as sleep duration decreased. Therefore, short sleepers were at a higher risk of being misclassified as normal or long sleepers, which might have led to an inability to detect an increased risk of breast cancer among such individuals. Of course, regardless of the direction of the bias, misclassification of exposure is an important problem to consider, and we appreciate that Yang et al highlighted this particular element of our report. Moreover, we also agree with the correspondents that it is important to measure sleep at different time points in order to get a better estimate of long-term sleep duration, and to consider other sleep characteristics and sleep-related factors, such as sleep quality and exposure to light at night. We are aware of the discrepancy between our findings and the melatonin hypothesis, which suggests that short sleep duration is associated with decreased levels of melatonin. Because melatonin is a molecule with anti-oestrogenic effects, decreased levels of melatonin may increase the risk of ER+ tumours (Blask, 2009). We found no association between sleep duration and hormone receptor-positive tumours, which is consistent with the only two studies that examined sleep duration in relation to breast cancer subtypes defined by hormone receptor status. Notably, both studies, an Australian case–control study and a study in the Women's Health Initiative, showed no relationship between sleep duration and ER+ tumours (Girschik et al, 2013; Vogtmann et al, 2013). In contrast, we found an increased risk associated with short sleep durations for hormone receptor-negative breast cancers. Although we cannot exclude the possibility that our finding is due to bias or chance, we believe that there are biological mechanisms that support this observed association. For example, short sleep and sleep deprivation have been associated with factors that may influence breast cancer risk independent of oestrogen pathways, such as metabolic dysfunction (Gangwisch et al, 2007) and chronic inflammation (Irwin et al, 2006). Again, we thank Yang et al for this letter and are glad that more studies, such as the population-based case–control study in Jiujiang city mentioned by Yang et al, are using objective measures along with questionnaires to better assess both the quantity and quality of sleep in relation to breast cancer risk and other health outcomes.

Sleep duration and breast cancer risk in the Breast Cancer Detection Demonstration Project follow-up cohort.

Background:Short sleep has been hypothesised to increase the risk of breast cancer. However, little is known about the association between sleep and different subtypes of breast cancer defined by hormone receptor status.Methods:Among 40 013 women in the Breast Cancer Detection Demonstration Project, including 1846 incident breast cancer cases, we prospectively examined self-reported weekday and weekend sleep duration in relation to breast cancer risk. We used multivariate Cox proportional hazards regression models to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results:We found no association between sleep and overall breast cancer. However, we observed a decreased risk of ER+PR+ breast cancer (RR <6 vs 8 – 9 h (95% CI): 0.54 (0.31, 0.93), P for trend, 0.003) with shorter sleep duration.Conclusions:Our finding does not support an association between sleep duration and overall breast cancer risk. However, the effect of sleep on different subtypes of breast cancer deserves further investigation.

Long-term overall and disease-specific mortality associated with benign gynecologic surgery performed at different ages

As bilateral salpingo-oophorectomy is frequently performed with hysterectomy for nonmalignant conditions, defining health outcomes associated with benign bilateral salpingo-oophorectomy performed at different ages is critical. We assessed mortality risk associated with benign total abdominal hysterectomy or bilateral salpingo-oophorectomy among 52,846 Breast Cancer Detection Demonstration Project follow-up study participants. Surgery and risk factor data were ascertained via baseline interview (1979-1986) and three questionnaires (1987-1998). During follow-up through December 2005 (mean, 22.1 y), 13,734 deaths were identified. We estimated hazard ratios (HRs) and 95% CIs for overall and disease-specific mortality for total abdominal hysterectomy or bilateral salpingo-oophorectomy performed by age 35, 40, 45, 50, or 55 years, compared with not having surgery, using landmark analyses and multivariable Cox regression. Undergoing bilateral salpingo-oophorectomy by age 35 years was associated with increased mortality risk (HR35 y, 1.20; 95% CI, 1.08-1.34), which decreased with age (HR40 y, 1.12; 95% CI, 1.04-1.21; HR45 y, 1.10; 95% CI, 1.03-1.17). Total abdominal hysterectomy alone performed by age 40 years was associated with increased mortality risk to a lesser extent (HR40 y, 1.08; 95% CI, 1.01-1.15). Analyses based on matched propensity scores related to having gynecologic surgery yielded similar results. Elevated mortality risks were largely attributable to noncancer causes. Benign gynecologic surgeries among young women are associated with increased mortality risk, which attenuates with age.

Abstract ES02-1: Pathology and biology of early breast lesions

Abstract It has been almost three decades since Dupont and Page published their seminal study relating breast cancer risk to the histologic findings in benign breast biopsies. Their initial observation, that proliferative lesions without atypia are associated with a 1.5-2-fold increase in breast cancer risk whereas atypical hyperplasias are associated with a 4-5-fold increase in risk, has been confirmed by other groups, including the Breast Cancer Detection Demonstration Project, the Nurses’ Health Study and the Mayo Clinic, among others. In aggregate, these groups have evaluated the relationship between the findings in benign breast biopsies and breast cancer risk in over 15,000 women and have additionally shown that several clinical, epidemiologic and histologic factors such as patient age, menopausal status, family history, time since biopsy, type and extent of atypical hyperplasia, and even the extent of involution of normal breast lobules modify the breast cancer risk among women with benign breast disease. More recent studies have examined the expression of various biomarkers and molecular alterations to determine their impact on breast cancer risk among women with benign breast lesions. While the expression of some biomarkers (including ERa, ERβ, TGFβ receptor II, COX2, and Ki67) has been reported to further stratify risk among women with proliferative breast lesions with and without atypia, all of these studies are limited by small patient numbers, due in part to the difficulty in capturing the microscopic lesions of interest for biomarker analysis. Given these limitations, an alternative approach is to study expression of biomarkers and molecular alterations in histologically normal breast tissue since normal epithelium is typically more abundant in benign breast biopsies than is lesional tissue. Using this approach, one recent study suggested that cytoplasmic expression of IGF-1R in normal breast epithelial cells identifies woman with benign breast disease at a particularly high risk for the subsequent development of breast cancer. This raises the possibility that targeting the IGF-1 pathway could be a novel strategy for breast cancer risk reduction. Other studies evaluating gene expression in normal breast epithelium have identified signatures that distinguish histologically normal breast epithelium obtained from reduction mammaplasty specimens from that obtained from breast cancer patients and, further, that distinguish normal breast epithelium in breasts with ER-positive cancers from that in breasts with ER-negative tumors. Data such as these raise the possibility that there may be identifiable, subtype-specific changes in gene expression within normal breast epithelial cells before histologic abnormalities are evident. It is likely that an integrated approach that combines epidemiology, histopathology, biomarker analysis and evaluation of molecular alterations will permit refinement of breast cancer risk assessment beyond that currently available and will, in turn, lead to new risk reduction strategies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES02-1.

Abstract A42: Intake of vitamins A, C, E, and folate and risk of ovarian cancer in a pooled analysis of 10 cohort studies

Abstract Vitamins A, C, E and folate have properties, such as modulation of DNA synthesis and repair, control of cellular differentiation and proliferation, as well as antioxidation, which are potentially cancer preventive. In a 2007 international panel review of the epidemiological literature published through 2006, the available data on the associations between intake of these vitamins and ovarian cancer risk were judged to be limited and inconclusive. Relatively few studies had been published and statistical power may have been limited in most studies. Among subsequent studies, sample sizes have been large in some though results remain inconsistent. In this project, we examined vitamin intakes from food only (dietary) and from food and supplements together (total) in relation to ovarian cancer risk by pooling the primary data from the following studies: Breast Cancer Detection Demonstration Project Follow-up Study, Canadian National Breast Screening Study, Cancer Prevention Study II Nutrition Cohort, Iowa Women's Health Study, Netherlands Cohort Study, New York State Cohort, New York University Women's Health Study, Nurses' Health Study, Nurses' Health Study II, and Swedish Mammography Cohort. Vitamin intakes were ascertained from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model, and then combined using a random-effects model. Multivariate models included total energy intake and other potential ovarian cancer risk factors. Among 501,857 women, 1,973 cases of ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies. When analyzed as continuous variables the RRs for dietary and total intakes of each of the vitamins were not significantly associated with ovarian cancer. For increments of intake defined by the mean of the standard deviation of the mean intake across studies, the pooled multivariate RRs (95% CI) for total intake of each vitamin were 1.02 (0.97-1.07) for each 1300 mcg/day increase in vitamin A, 1.01 (0.99-1.04) for each 400 mg/day increase in vitamin C, 1.02 (0.97-1.06) for each 130 mg/day increase in vitamin E and 1.01 (0.96-1.07) for each 250 mcg/day increase in folate. When vitamin intakes were analyzed as categorical variables defined by study-specific quintiles of intake, the results were consistent with the continuous analyses and indicated no significant association. There was no evidence of statistically significant heterogeneity between studies in any of the analyses. Also, the pooled RRs did not vary greatly by levels of parity, oral contraceptive use, postmenopausal hormone use, smoking status or alcohol consumption, nor did associations greatly differ by histological type. We also examined use of specific vitamin supplements and multivitamins and did not observe a significant association with risk of ovarian cancer overall; the pooled multivariate RR (95% CI) for multivitamin use versus non-use was 1.00 (0.89-1.12). This large pooled analysis suggests that vitamins A, C, E and folate are not associated with the risk of ovarian cancer. Citation Format: Anita Koushik, Stephanie A. Smith-Warner. Intake of vitamins A, C, E, and folate and risk of ovarian cancer in a pooled analysis of 10 cohort studies. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A42.

Beyond Breast Cancer: Mammographic Features and Mortality Risk in a Population of Healthy Women

BackgroundBreast fibroglandular (dense) tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features.MethodsWe evaluated relationships between nondense (fatty) breast area and dense area with all-cause mortality in 4,245 initially healthy women from the Breast Cancer Detection Demonstration Project; 1,361 died during a mean follow-up of 28.2 years. Dense area and total breast area were assessed using planimeter measurements from screening mammograms. Percent density reflects dense area relative to breast area and nondense area was calculated as the difference between total breast area and dense area. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.ResultsIn age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference) while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference). Associations were not attenuated with adjustment for race, education, mammogram type (x-ray or xerogram), smoking status, diabetes and heart disease. With additional adjustment for body mass index, associations were diminished for all features but remained statistically significant for dense area (HR 0.94, 95% CI 0.89-0.99, per SD difference) and percent density (HR 0.93, 95% CI 0.87-0.98, per SD difference).ConclusionsThese data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk.

Frequency, Digital Technology, and the Efficiency of Screening Mammography

Editorials18 October 2011Frequency, Digital Technology, and the Efficiency of Screening MammographyPhilippe Autier, MDPhilippe Autier, MDFrom International Prevention Research Institute, 69006 Lyon, France.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-8-201110180-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The optimal frequency of screening mammography has been a topic of debate for decades. In the wake of the Greater New York Health Insurance Plan trial, which tested annual mammography plus breast physical examination, the Breast Cancer Detection Demonstration Project (conducted from 1973 to 1981 in 283 222 U.S. women aged 35 to 74 years from 29 U.S. centers) also adopted an annual screening schedule (1). In 1985, the Swedish Two-County Trial (2) provided the first evidence that mammography screening alone could reduce breast cancer mortality. The screening schedule in this trial was mammography 2 to 4 times every 24 months ...

Bone Fractures and Incident Epithelial Ovarian Cancer in a Prospective Cohort Study

Osteoporosis and osteoporotic fractures are hypothesized to reflect circulating hormone levels in older women and have been inversely associated with breast and endometrial cancers. However, associations between fractures and ovarian cancer, another hormonal cancer, have not been examined. Therefore, we conducted a prospective study among women in the Breast Cancer Detection Demonstration Project Follow-up Study. Fractures after age 45 were assessed using two questionnaires from 1987 to 1995. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models, adjusting for potential confounders. Fracture location was used to further evaluate the fractures most likely to be osteoporotic. Among 36,115 women with up to 11 years of follow-up (average follow-up was 8.3 years), there were 151 cases of incident ovarian cancer. Fractures were reported by 19% (n = 6,919) of women. Ovarian cancer risk was not associated with any (RR = 1.13, 95% CI 0.74-1.71) or likely osteoporotic (RR = 1.05, 95% CI 0.65-1.69) fractures. Among never users of postmenopausal hormones, the association between any fracture and ovarian cancer (RR = 1.21, 95% CI 0.55-2.65, n = 50 cases) also was statistically nonsignificant. Data from this large, prospective study do not support an association between fractures and ovarian cancer risk.

Menopausal Hormone Therapy and Risk of Colorectal Cancer

We evaluated colorectal cancer risk associated with the duration and recency of specific menopausal hormone therapy formulations (i.e., unopposed estrogen versus estrogen plus progestin) and regimens (i.e., sequential versus continuous estrogen plus progestin use) among 56,733 postmenopausal women participating in the Breast Cancer Detection Demonstration Project follow-up study. Hormone therapy use and other risk factors were ascertained through telephone interviews and mailed questionnaires from 1979 to 1998. The final cancer group included 960 women who were identified from self-report, medical records, state registry data, and the National Death Index. Poisson regression was used to generate multivariable rate ratios (RR) and 95% confidence intervals (95% CI). We observed a decreased risk of colorectal cancer among ever users of unopposed estrogen therapy (RR, 0.83; 95% CI, 0.70-0.99). Among estrogen users, the largest reduced risk was observed for current users (RR, 0.75; 95% CI, 0.54-1.05) and users of >or=ten years duration (RR, 0.74; 95% CI, 0.56-0.96). We found a reduced risk among users of estrogen plus progestin therapy (RR, 0.78; 95% CI, 0.60-1.02), with sequential regimen users (progestin <15 days per cycle) having the largest risk reduction (RR, 0.64; 95% CI, 0.43-0.95). Past users of >or=5 years ago (RR, 0.55; 95% CI, 0.32-0.98) had the largest risk reduction. In this study, estrogen plus progestin use, especially sequential regimen use, was associated with the largest overall reduction of colorectal cancer risk.

Abstract A79: Hormonal factors and breast cancer risk in nulliparous women

Abstract A79 Background Nulliparous women are a growing population in the U.S. that is known to be at elevated risk for breast cancer. A term pregnancy is believed to exert a protective effect on the ductal structures in the breast through terminal differentiation. It is biologically plausible that limited ductal maturation in nulliparous women renders the breast more susceptible to the effects of hormonal factors. Methods We assessed the association between hormonal and other factors and breast cancer risk by parity among postmenopausal women. Data were combined from four prospective cohort studies [The Breast Cancer Detection Demonstration Project Follow-up Study, the NIH-AARP Diet and Health Study, The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, and The United States Radiologic Technologist Study]. Each dataset was analyzed using multivariable Cox Proportional Hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) separately for nulliparous and parous women for known risk factors. Study-specific results were combined using a meta-analytic random effects model. Results A total of 1,611 breast cancers were reported among 32,636 nulliparous women and 8,284 breast cancers among 207,763 parous women. The meta-analytic HRs for the one of the strongest risk factors, current use of menopausal hormone therapy for ≥5 years, were 1.46 (95% CI: 1.10-1.82) and 1.50 (95% CI: 1.42-1.59) for nulliparous and parous women, respectively. Patterns of risk were similar for nulliparous and parous women for other factors including ages at menarche and last menstrual period, body mass index, family history of breast cancer, and benign breast disease. Some study-specific variability was detected. Conclusions Similar associations between hormonal risk factors and breast cancer were observed for nulliparous and parous women. However, given their elevated baseline risk, these risk factors are likely to contribute to a greater absolute risk of breast cancer among nulliparous women. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A79.

Prospective study of physical activity and risk of postmenopausal breast cancer

IntroductionTo prospectively examine the relation of total, vigorous and non-vigorous physical activity to postmenopausal breast cancer risk.MethodsWe studied 32,269 women enrolled in the Breast Cancer Detection Demonstration Project Follow-up Study. Usual physical activity (including household, occupational and leisure activities) throughout the previous year was assessed at baseline using a self-administered questionnaire. Postmenopausal breast cancer cases were identified through self-reports, death certificates and linkage to state cancer registries. A Cox proportional hazards regression was used to estimate the relative risk and 95% confidence intervals of postmenopausal breast cancer associated with physical activity.ResultsDuring 269,792 person-years of follow-up from 1987 to 1998, 1506 new incident cases of postmenopausal breast cancer were ascertained. After adjusting for potential risk factors of breast cancer, a weak inverse association between total physical activity and postmenopausal breast cancer was suggested (relative risk comparing extreme quintiles = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.21). That relation was almost entirely contributed by vigorous activity (relative risk comparing extreme categories = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.08). The inverse association with vigorous activity was limited to women who were lean (ie, body mass index <25.0 kg/m2: relative risk = 0.68; 95% confidence interval = 0.54 to 0.85). In contrast, no association with vigorous activity was noted among women who were overweight or obese (ie, body mass index ≥ 25.0 kg/m2: relative risk = 1.18; 95% confidence interval = 0.93 to 1.49; p for interaction = 0.008). Non-vigorous activity showed no relation to breast cancer (relative risk comparing extreme quintiles = 1.02; 95% confidence interval = 0.87 to 1.19; p for trend = 0.86). The physical activity and breast cancer relation was not specific to a certain hormone receptor subtype.ConclusionsIn this cohort of postmenopausal women, breast cancer risk reduction appeared to be limited to vigorous forms of activity; it was apparent among normal weight women but not overweight women, and the relation did not vary by hormone receptor status. Our findings suggest that physical activity acts through underlying biological mechanisms that are independent of body weight control.

Breast Cancer Relative Hazard Estimates From Case–Control and Cohort Designs With Missing Data on Mammographic Density

We analyzed data from the Breast Cancer Detection Demonstration Project (BCDDP) to obtain multivariate relative hazard models for breast cancer that included mammographic density (MD) in addition to standard risk factors. Data from the BCDDP were collected from a stratified case–control study in the screening phase (1973–1980) and from follow-up of three subcohorts in the follow-up phase (1980–1995). For both phases, MD measurements were only available for about half the women who developed breast cancer (cases) and a small fraction of noncases. We used a logistic regression model for the stratified case–control study and developed a general pseudo-likelihood approach to accommodate missing covariate data (MD) by adapting the method of Scott and Wild and Breslow and Holubkov. We showed that this method was substantially more efficient than a previously proposed weighted-likelihood method. We assumed piecewise exponential models for the analysis of each subcohort, with the missing covariate (MD) distribution conditional on the observed information modeled with polytomous logistic regression. We developed an EM algorithm for estimation, which allowed for time-varying covariates, incomplete follow-up, and left truncation. We analyzed the three follow-up subcohorts separately and then combined the relative hazard models from the case–control and cohort data. The final model included main effects for MD, weight, age at first live birth, number of previous breast biopsies, and number of sisters or mother with breast cancer and was more discriminating (higher concordance) than the original model of Gail et al., which included standard risk factors but not MD. In a separate work, we combined this relative hazard model with other data to project absolute breast cancer risk.

A prospective study of physical activity and the risk of pancreatic cancer among women (United States)

BackgroundSeveral epidemiologic studies have examined the association between physical activity and pancreatic cancer risk; however, the results of these studies are not consistent.MethodsThis study examined the associations of total, moderate, and vigorous physical activity to pancreatic cancer in a cohort of 33,530 U.S. women enrolled in the Breast Cancer Detection Demonstration Project (BCDDP). At baseline (1987–1989), information on physical activity over the past year was obtained using a self-administered questionnaire. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals of pancreatic cancer risk.Results70 incident cases of pancreatic cancer were ascertained during 284,639 person years of follow-up between 1987–1989 and 1995–1998. After adjustment for age, body mass index, smoking status, history of diabetes, and height, increased physical activity was related to a suggestively decreased risk of pancreatic cancer. The RRs for increasing quartiles of total physical activity were 1.0, 0.80, 0.66, 0.52 (95% CI = 0.26, 1.05; ptrend = 0.05). This association was consistent across subgroups defined by body mass index and smoking status. We also observed statistically non-significant reductions in pancreatic cancer risk for women in the highest quartile of moderate (RR = 0.57; 95% CI = 0.26, 1.26) and highest quartile of vigorous physical activity (RR = 0.63; 95% CI = 0.31, 1.28) compared to their least active counterparts.ConclusionOur study provides evidence for a role of physical activity in protecting against pancreatic cancer.

Dietary carbohydrate, glycemic index, and glycemic load and the risk of colorectal cancer in the BCDDP cohort

There is considerable support for associations between insulin and IGF-I levels and colorectal cancer. Diet may relate to colorectal cancer through this mechanism, for example, diets high in glycemic index, glycemic load and/or carbohydrate are hypothesized to increase insulin load and the risk of insulin resistance, hyperinsulinemia. Case-control studies support this hypothesis, but prospective cohorts have had mixed results. In the Breast Cancer Detection Demonstration Project (BCDDP) follow-up cohort of 45,561 women, we used Cox proportional hazards regression to assess the distribution of 490 incident cases of colorectal cancer ascertained during 8.5 years of follow-up across quintiles of carbohydrate intake, glycemic index, and glycemic load. We also stratified by combined BMI and physical activity levels. We found reductions in colorectal cancer risk for diets high in carbohydrate (RR for Q5 vs. Q1 = 0.70, 95% CI: 0.50-0.97) and glycemic index (0.75, 95% CI: 0.56-1.00), and no significant association for glycemic load (0.91, 95% CI: 0.70-1.20). Inverse associations were weakest in normal weight active persons. The inverse association for glycemic index was strongest for the portion from dairy food. These results do not support an association between diets high in carbohydrate, glycemic index or glycemic load and colorectal cancer.

Weight, Height, and Body Mass Index and Risk for Ovarian Cancer in a Cohort Study

Reported associations between ovarian cancer and body size are inconsistent. We assessed ovarian cancer and anthropometry in the Breast Cancer Detection Demonstration Project Follow-Up Study. The 46,026 participants completed a baseline interview and mailed questionnaires between 1979 and 1998. By using multiple sources, we identified 346 incident ovarian cancers during follow-up. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) to estimate relative risks for developing ovarian cancer associated with height and weight (measured 1973 to 1980) and self-reported current and usual adult weight (collected during follow-up). Neither taller height (> or =66 versus <62 inches; RR, 0.90; 95% CI, 0.64-1.26) nor greater weight (> or =161 versus < or =120 lbs; RR, 1.09; 95% CI, 0.77-1.55) was associated with ovarian cancer. Compared with normal weight (body mass index [BMI], 18.5 to 24.9 kg/m(2)), overweight (BMI, 25 to 29.9 kg/m(2); RR, 1.00; 95% CI, 0.78-1.29) and obesity (BMI, 30 to 34.9 kg/m(2); RR, 0.94; 95% CI, 0.59-1.48) were not associated with ovarian cancer. Severe obesity (BMI > or = 35 kg/m(2)) produced a nonsignificantly elevated RR (1.55; 95% CI, 0.84-2.84). Associations with histologic types and statistical interactions with menopausal status and hormone therapy use were null. Based on height and weight measured before baseline, overweight and obesity were not significantly associated with ovarian cancer in this cohort.

Reproductive factors, exogenous hormone use and bladder cancer risk in a prospective study

Sex is a consistent predictor of bladder cancer: men experience 2-4-fold higher age-adjusted rates than women in the U.S. and Europe. The objective of this study was to examine whether hormone-related factors are associated with bladder cancer in women. We examined parity, age at menarche, age at first birth, age at menopause, oral contraceptive use and menopausal hormone therapy (HT) use and bladder cancer risk in the Breast Cancer Detection Demonstration Project Follow-Up Study. Endpoint and exposure information was collected on 54,308 women, using annual telephone interviews (1980-86) and 3 mailed, self-administered questionnaires (1987-98). During an average follow-up time of 15.3 years, 167 cases of bladder cancer were identified. Univariate and adjusted rate ratios (RRs) were estimated using Poisson regression. Parity, age at menarche, age at first birth, age at menopause, and oral contraceptive use were not associated with bladder cancer risk. The majority of menopausal women who took HT used estrogen therapy (ET). Postmenopausal women with less than 4 years, 4-9 years, 10-19 years and 20 or more years of ET use had RRs of 1.55 (95% CI = 0.96-2.51), 1.00 (95% CI = 0.49-2.04), 1.23 (95% CI = 0.62-2.43) and 0.57 (95% CI = 0.14-2.34), respectively, compared with nonusers (p = 0.50). Findings from this study are not consistent with the hypothesis that hormone-related factors in women are associated with bladder cancer.

Projecting Absolute Invasive Breast Cancer Risk in White Women With a Model That Includes Mammographic Density

To improve the discriminatory power of the Gail model for predicting absolute risk of invasive breast cancer, we previously developed a relative risk model that incorporated mammographic density (DENSITY) from data on white women in the Breast Cancer Detection Demonstration Project (BCDDP). That model also included the variables age at birth of first live child (AGEFLB), number of affected mother or sisters (NUMREL), number of previous benign breast biopsy examinations (NBIOPS), and weight (WEIGHT). In this study, we developed the corresponding model for absolute risk. We combined the relative risk model with data on the distribution of the variables AGEFLB, NUMREL, NBIOPS, and WEIGHT from the 2000 National Health Interview Survey, with data on the conditional distribution of DENSITY given other risk factors in BCDDP, with breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, and with national mortality rates. Confidence intervals (CIs) accounted for variability of estimates of relative risks and of risk factor distributions. We compared the absolute 5-year risk projections from the new model with those from the Gail model on 1744 white women. Attributable risks of breast cancer associated with DENSITY, AGEFLB, NUMREL, NBIOPS, and WEIGHT were 0.779 (95% CI = 0.733 to 0.819) and 0.747 (95% CI = 0.702 to 0.788) for women younger than 50 years and 50 years or older, respectively. The model predicted higher risks than the Gail model for women with a high percentage of dense breast area. However, the average risk projections from the new model in various age groups were similar to those from the Gail model, suggesting that the new model is well calibrated. This new model for absolute invasive breast cancer risk in white women promises modest improvements in discriminatory power compared with the Gail model but needs to be validated with independent data.

Relationship Between Calcium, Lactose, Vitamin D, and Dairy Products and Ovarian Cancer

: Few prospective studies of the relationship between intake of dairy foods, calcium, vitamin D, and lactose and ovarian cancer have been conducted, and results have been largely inconsistent. Two recent studies found significant increased risk with frequent dairy consumption and perhaps with high intakes of calcium or lactose. The authors investigated the association between these foods and nutrients and ovarian cancer risk among 31,925 subjects in the Breast Cancer Detection Demonstration Project follow-up cohort. Multivariable (MV) relative risks (RRs) adjusted for age, parity, and other factors were estimated using Cox proportional hazards models. Over an average follow-up of 8.3 yr, 146 incident ovarian cancer cases were confirmed. Higher intakes of total dairy food (comparing four or more servings per day vs. less than one serving per day) were associated with a statistically significant decreased risk of ovarian cancer, although the trend was not significant (MV RR = 0.42; 95% confidence interval (CI) = 0.20–0.89; P for trend = 0.07). Comparing extreme quartiles, we observed a statistically nonsignificant inverse association between high dietary calcium intake and ovarian cancer (RR = 0.67; 95% CI = 0.43, 1.04; P for trend = 0.08). No statistically significant relations were found for consumption of specific dairy foods, lactose, or vitamin D and ovarian cancer risk. The possibility of a decreased risk of ovarian cancer for dietary calcium merits further evaluation.

Family history of breast cancer as a risk factor for ovarian cancer in a prospective study

A family history of breast cancer has been associated with increased ovarian cancer risk. However, few studies have assessed risk according to characteristics that suggest an inherited cancer susceptibility disorder, such as earlier-than-usual age at cancer diagnosis, family members with double primary cancers of different types, multiple relatives with cancer, and cancer in both members of paired organs. Ovarian cancer risk was assessed according to a detailed breast cancer family history among 49,975 participants in the Breast Cancer Detection Demonstration Project Breast Cancer Defection Demenstration Project (BCDDP) Follow-up Study (1979-1998). In all, 362 incident ovarian cancers were identified during follow-up and rate ratios (RRs) were calculated by Poisson regression. RESULTS.: Breast cancer in a first- or second-degree relative was associated with increased risk of ovarian cancer (RR = 1.4; 95% confidence interval [CI] = 1.1-1.7). Having 2 or more affected first-degree relatives was associated with increased risk (RR = 1.8; 95% CI = 1.1-2.8), especially for women diagnosed with ovarian cancer before age 60 (RR = 4.2; 95% CI = 1.9-9.2) or with a personal history of breast cancer (RR = 3.7; 95% CI 1.8-7.7). Risk was also particularly high for women with 2 or more first-degree relatives with breast cancer and at least 1 affected relative diagnosed before age 50 (RR = 2.6; 95% CI = 1.4-4.8) or with bilateral breast cancer (RR = 4.2; 95% CI = 1.7-10). A detailed breast cancer family history as well as an individual's age and personal history of breast cancer are useful for identifying women at elevated genetic risk of ovarian cancer.

Physical activity and the risk of colon cancer among women: A prospective cohort study (United States)

Physical activity has frequently been reported to decrease the risk of colon cancer in men, but data on the relation of physical activity to colon cancer risk in women have generally been less consistent. To further investigate the relationship of physical activity with colon cancer risk in women, we studied a cohort of 31,783 US women participating in the Breast Cancer Detection Demonstration Project Follow-up Study. Information on daily physical activity over the past year was ascertained using a self-administered questionnaire at study baseline. The Cox proportional hazards model was used to estimate relative risks (RRs) relating physical activity to the risk of incident colon cancer. During 270,325 person-years of follow-up, 243 colon cancer cases were identified. No association was observed between physical activity and the subsequent risk of colon cancer. The multivariable RRs of colon cancer across increasing quintiles of total physical activity were 1.0, 1.45, 1.16, 1.27 and 1.15 (95% CI: 0.76, 1.75; p(trend) = 0.77). The multivariable RRs comparing women at the extremes of moderate and vigorous physical activity, respectively, were 1.07 (95% CI: 0.70, 1.62) and 1.10 (95% CI: 0.78, 1.55). The relationship between physical activity and colon cancer risk did not vary by anatomic subsite or across subgroups defined by age, body mass, dietary fiber intake, menopausal status, menopausal hormone use or aspirin use. The results of this large prospective cohort study among women do not support the hypothesis that physical activity is related to a lower incidence of colon cancer.