Search

To maximize statistical power in studies of mammographic density and breast cancer, it is advantageous to combine data from several studies, but standardization of the density assessment is desirable. Using data from 4 case-control studies, we describe the process of reassessment and the resulting correlation between values, identify predictors of differences in density readings, and evaluate the strength of the association between mammographic density and breast cancer risk using different representations of density values. The pooled analysis included 1,699 cases and 2,422 controls from California (1990-1998), Hawaii (1996-2003), Minnesota (1992-2001), and Japan (1999-2003). In 2010, a single reader reassessed all images for mammographic density using Cumulus software (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada). The mean difference between original and reassessed percent density values was -0.7% (95% confidence interval: -1.1, -0.3), with a correlation of 0.82 that varied by location (r = 0.80-0.89). Case status, weight status, age, parity, density assessment method, mammogram view, and race/ethnicity were significant determinants of the difference between original and reassessed values; in combination, these factors explained 9.2% of the variation. The associations of mammographic density with breast cancer and the model fits were similar using the original values and the reassessed values but were slightly strengthened when a calibrated value based on 100 reassessed radiographs was used.

Female steroid hormones are hypothesized to play a protective role in pancreatic cancer risk. However, results from epidemiologic studies that examined hormone-related exposures have been inconsistent. The California Teachers Study is a cohort study of female public school professionals that was established in 1995-1996. Of the 118,164 eligible study participants, 323 women were diagnosed with incident invasive pancreatic cancer through December 31, 2009. Multivariable Cox proportional hazards regression methods were used to estimate hazard ratios and 95% confidence intervals for the association of pancreatic cancer risk with reproductive factors and exogenous hormone use. Current users of estrogen-only therapy at baseline (1995-1996) had a lower risk of pancreatic cancer than did participants who had never used hormone therapy (hazard ratio = 0.59, 95% confidence interval: 0.42, 0.84). Use of estrogen-plus-progestin therapy was not associated with the risk of pancreatic cancer. A longer duration of oral contraceptive use (≥10 years of use compared with never use) was associated with an increased risk of cancer (hazard ratio = 1.72, 95% confidence interval: 1.19, 2.49). Reproductive factors, including age at menarche, parity, breastfeeding, and age at menopause, were not associated with pancreatic cancer risk. Our results suggest that increased estrogen exposure through estrogen-only therapy may reduce pancreatic cancer risk in women.

Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P(trend) < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years.

Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.

Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995-1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18-22 years, at ages 30-35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.

Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22-84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61-1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.

Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.

Mammographic density is an independent risk factor for breast cancer. In postmenopausal women, higher levels of endogenous sex steroids are associated with an increased risk of breast cancer. Limited prior data suggest that endogenous sex steroids either are not associated (total estradiol and progesterone) or are negatively associated (free estradiol) with higher mammographic density. To analyze the associations between endogenous sex steroids and mammographic density, the authors conducted a 1998-2005 cross-sectional analysis of baseline clinical trial data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial for US women who had not used hormone therapy for at least 3.1 months prior to baseline. In models adjusted for age, body mass index, parity, prior use of hormone therapy, time since last use of hormone therapy, and the interaction between prior hormone therapy use and time since last hormone therapy use, higher levels of estrone (beta = 0.0013, p = 0.014), estradiol (beta = 0.0009, p = 0.009), and bioavailable estradiol (beta = 0.0021, p = 0.018) were statistically significantly related to greater mammographic density. (Beta coefficients express the increment in mammographic density per-unit increment (pg/ml) of each hormone.) These results suggest that some sex steroids may increase the risk of breast cancer by stimulating breast epithelial or stromal proliferation, which appears on a mammogram as higher density.

Breast cancer incidence rates in the United States are substantially lower among Asian-American women than among White or African-American women. The authors determined whether mammographic density reflects these ethnic differences by evaluating mammograms from 442 White, African-American, and Asian-American women without breast cancer who served as controls in one of two population-based, breast cancer case-control studies conducted in Los Angeles, California, in 1994-1998. Absolute and percent mammographic densities were determined with a previously developed and validated computer-assisted method. Data were analyzed using multiple regression methods. Mean age-adjusted percent mammographic density was significantly higher in Asian Americans (35.9%) than in African Americans (27.8%, p < 0.05) but was no longer significant after further adjustment for body mass index. After adjustment for age, body mass index, selected menstrual/reproductive factors, and family history, absolute mammographic density was statistically significantly lower in Asian Americans than in African Americans (p < 0.05) but not than in Whites. The ethnic difference in absolute mammographic density was particularly evident among women older than age 50 years. Additional adjustment for breast size reduced these ethnic differences. This study suggests that absolute but not percent mammographic density reflects the lower breast cancer incidence rates of Asian Americans in relation to those of African Americans and Whites.

Breast cancer incidence has historically been 4-7 times higher in the United States than in Asia. A previous study by the authors in Asian-American women demonstrated a substantial increase in breast cancer risk in women who migrated from Asia to the United States, with the risk almost doubling during the first decade after migration. Increased use of oral contraceptives soon after migration to the United States could possibly explain this rapid rise in risk. In a population-based case-control study of Chinese, Filipino, and Japanese-American women, aged 20-55 years, who lived in San Francisco-Oakland, California; Los Angeles, California; and Oahu, Hawaii during 1983-1987, 597 cases (70% of those eligible) and 966 controls (75%) were interviewed. Controls were matched to cases on age, ethnicity, and area of residence. Oral contraceptive (OC) use increased with time since migration; 15.0% of Asian-born women who had been in the West <8 years, 33.4% of Asian-born women who had been in the West > or =8 years, and 49.6% of Asian women born in the West had ever used OCs. However, duration of OC use (adjusted for age, ethnicity, study area, years since migration, education, family history of breast cancer and age at first full-term birth) was not associated with increased risk of breast cancer. Moreover, neither OC use before age 25 years nor before first full-term birth was associated with increased risk. Results were unchanged when restricted to women under age 45 years or under age 40 years. After adjustment for duration of OC use, women who had been in the United States > or =8 years were still at almost twice the risk of breast cancer compared with women who had been in the United States 2-7 years. This study suggests that OC use cannot explain the elevated risk observed in Asian women who migrated to the United States > or =7 years ago.

To identify systematically the nutrient and food group intakes associated with a low-fat diet, the authors used the detailed dietary information collected from 10,306 individuals aged 32-86 years in the 1982-1984 National Health Epidemiologic Follow-up Study. Intakes of vitamin C and percentages of calories from carbohydrates, dietary fiber, poultry, low-fat dairy products, fruits, vegetables, cereals, and whole grains were markedly higher, while intakes of protein, total fat, saturated fat, oleic and linoleic acids, cholesterol, sodium, all red meats, high-fat dairy products, eggs, nuts, white bread, fried potatoes, desserts, fats, and oils were much lower in the quartile with the lowest percentage of calories from fat. These dietary patterns associated with a low-fat diet were essentially constant across strata of age, sex, race, and socioeconomic status. This study suggests that individuals on a low-fat diet substitute certain carbohydrate-rich foods such as fruits and vegetables for fat. Given these associations between low-fat diets and other dietary factors independently associated with certain cancers, these dietary factors should be considered potential confounders in studies of dietary fat and these cancers.