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Mammographic density, i.e., the radiographic appearance of the breast, is a strong predictor of breast cancer risk. To determine whether the association of breast density with breast cancer is modified by a first-degree family history of breast cancer (FHBC) in women of white and Asian ancestry, we analyzed data from four case–control studies conducted in the USA and Japan. The study population included 1,699 breast cancer cases and 2,422 controls, of whom 45 % reported white (N = 1,849) and 40 % Asian (N = 1,633) ancestry. To standardize mammographic density assessment, a single observer re-read all mammograms using one type of interactive thresholding software. Logistic regression was applied to estimate odds ratios (OR) while adjusting for confounders. Overall, 496 (12 %) of participants reported a FHBC, which was significantly associated with breast cancer risk in the adjusted model (OR 1.51; 95 % CI 1.23–1.84). There was a statistically significant interaction on a multiplicative scale between FHBC and continuous percent density (per 10 % density: p = 0.03). The OR per 10 % increase in percent density was higher among women with a FHBC (OR 1.30; 95 % CI 1.13–1.49) than among those without a FHBC (OR 1.14; 1.09–1.20). This pattern was apparent in whites and Asians. The respective ORs were 1.45 (95 % CI 1.17–1.80) versus 1.22 (95 % CI 1.14–1.32) in whites, whereas the values in Asians were only 1.24 (95 % CI 0.97–1.58) versus 1.09 (95 % CI 1.00–1.19). These findings support the hypothesis that women with a FHBC appear to have a higher risk of breast cancer associated with percent mammographic density than women without a FHBC.

Objective To identify factors that mediate or moderate the effects of exercise on postmenopausal sex hormone concentrations. Methods Postmenopausal women were randomized to 12 months of aerobic exercise for 200 min/week (n = 160) or to a control group (n = 160). Intention-to-treat analyses were performed using general linear models with sex hormone concentrations at 6 and 12 months as the outcome. Mediation by adiposity and insulin was investigated by examining changes in effect estimates after adjustment for changes in these factors over 12 months. Moderation was studied as the interaction between group assignment and eight baseline characteristics. Results Intervention effects on sex hormone–binding globulin (SHBG) and estradiol changes were attenuated with adjustment for change in overall body fat, while there was less attenuation adjusting for intra-abdominal fat change. Intervention effects on SHBG levels were unaffected by adjustment for insulin change. Significant interactions were identified between treatment and physical fitness (for SHBG and testosterone) and age (for testosterone), implying subgroup differences in intervention effect. Conclusions Our data suggest that overall fat loss partially mediated exercise-induced changes in estradiol and SHBG concentrations. No previous RCT in postmenopausal women has studied moderators of exercise-induced sex hormone changes; therefore, future studies are needed to corroborate our results.

The main objective was to examine the association between simple hysterectomy (without bilateral oophorectomy) and breast cancer risk. Because hysterectomy prevalence varies by ethnicity, the secondary objective was to examine whether inclusion of women with hysterectomies affects the estimates of breast cancer risk by ethnicity.The Multiethnic Cohort study was assembled between 1993 and 1996 and included 68,065 women from Hawaii and Los Angeles, aged 45-75 years, without any missing information or bilateral oophorectomy. Hysterectomy status was self-reported. After 7.7 years median follow-up, 1,862 cases of invasive breast cancer were identified. Proportional hazards models were used to estimate relative risks (RR) while controlling for known risk factors.Prevalence of simple hysterectomy varied from 12% to 29% among the ethnic groups (White, African American, Native Hawaiian, Japanese American, and Latina). Overall, hysterectomy was not associated with breast cancer risk (RR = 0.98). Although the RRs were nonsignificantly elevated by 15% in White women and nonsignificantly reduced by 15% in Latinas of non-US origin, the variation by ethnicity was not significant (p(interaction) = 0.48). The breast cancer risk associated with ethnicity was very similar when estimated with and without women with hysterectomies.This study suggests that simple hysterectomy status does not alter breast cancer risk. Therefore, inclusion of women with simple hysterectomies does not substantially change estimated risk of breast cancer by ethnicity.