Key PointsQuestionWhat is the association between body mass index and risk for breast cancer diagnosed before menopause?FindingIn this large pooled analysis of data on 758 592 premenopausal women, an inverse association of breast cancer risk with body mass index at 18 through 54 years of age was found, most strongly for body mass index at ages 18 through 24 years. The inverse association was strongest for hormone receptor–positive breast cancer, was evident across the entire distribution of body mass index, and did not materially vary by attained age or other characteristics of women.MeaningIncreased adiposity, in particular during early adulthood, may be associated with reductions in the risk of premenopausal breast cancer.

Background Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. Methods Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. Results Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2–4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5–<9 kg lost: HR = 0.75, 95% CI = 0.63 to 0.90; ≥9 kg lost: HR = 0.68, 95% CI = 0.50 to 0.93). Women who lost at least 9 kg and gained back some (but not all) of it were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight. Conclusions These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.

Abstract Background There is growing evidence that breast cancer survivors have higher cardiovascular disease (CVD) mortality relative to the general population. Information on temporal patterns for all-cause and CVD mortality among breast cancer survivors relative to cancer-free women is limited. Methods All-cause and CVD-related mortality were compared in 628 women with breast cancer and 3,140 age-matched cancer-free women within CLUE II, a prospective cohort. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression for all-cause mortality, and Fine and Gray models for CVD-related mortality to account for competing risks. Results Over 25 years of follow-up, 916 deaths occurred (249 CVD-related). Breast cancer survivors had an overall higher risk of dying compared to cancer-free women (HR = 1.79, 95% CI = 1.53-2.09) irrespective of time since diagnosis, tumor stage, estrogen receptor (ER) status, and older age at diagnosis (≥70 years). Risk of death was greatest among older survivors 15 or more years after diagnosis (HR = 2.69, 95% CI = 1.59-4.55). CVD (69.1% ischemic heart disease) was the leading cause of death among cancer-free women and the second among survivors. Survivors had an increase in CVD-related deaths compared to cancer-free women beginning at 8 years after diagnosis (HR = 1.65, 95% CI = 1.00-2.73) with the highest risk among older survivors (HR = 2.24, 95% CI = 1.29-3.88) and after ER-positive disease (HR = 1.85, 95% CI = 1.06-3.20). Conclusions Breast cancer survivors continue to have an elevated mortality compared to the general population for many years after diagnosis. Preventing cardiac deaths, particularly among older breast cancer patients, could lead to significant reductions in mortality.

The transcription factor 7-like 2 (TCF7L2) gene is part of the Wnt/β-catenin signaling pathway and plays a critical role in cell development and growth regulation. TCF7L2 variants rs12255372 and rs7903146 have been associated with risk of Type 2 diabetes. Few epidemiological studies have examined the association between TCF7L2 and breast cancer risk. We investigated the associations between 25 TCF7L2 single nucleotide polymorphisms (SNPs) and breast cancer in Hispanic and non-Hispanic white (NHW) women from the 4-Corner’s Breast Cancer Study, the San Francisco Bay Area Breast Cancer Study, and the Mexico Breast Cancer Study. A total of 4,703 Hispanic (2,093 cases, 2,610 controls) and 3,031 NHW (1,431 cases, 1,600 controls) women were included. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated using logistic regression to estimate the association between the TCF7L2 SNPs and breast cancer risk. We also examined effect modification by self-reported ethnicity, genetic admixture, and diabetes history. After adjusting for multiple comparisons, four TCF7L2 SNPs were significantly associated with breast cancer overall: rs7903146 (ORTT 1.24; 95 % CI 1.03–1.49), rs3750805 (ORAT/TT 1.15; 95 % CI 1.03–1.28), rs7900150 (ORAA 1.23; 95 % 1.07–1.42), and rs1225404 (ORCC 0.82; 95 % 0.70–0.94). Among women with a history of diabetes, the TT genotype of rs3750804 increased breast cancer risk (OR, 2.46; 95 % CI 1.28–4.73). However, there was no association among women without a diabetes history (OR, 1.06; 95 % CI 0.85–1.32). We did not find significant interactions by ethnicity or by genetic admixture. Findings support an association between TCF7L2 and breast cancer and history of diabetes modifies this association for specific variants.