Background: Factors related to improving outcomes in breast cancer survivors are of increasing public health significance. We examined postdiagnosis weight change in relation to mortality risk in a cohort of breast cancer survivors. Methods: We analyzed data from a cohort of 3,993 women with ages 20 to 79 years living in New Hampshire, Massachusetts, or Wisconsin with invasive nonmetastatic breast cancers diagnosed in 1988 to 1999 identified through state registries. Participants completed a structured telephone interview 1 to 2 years after diagnosis and returned a mailed follow-up questionnaire in 1998 to 2001 that addressed postdiagnosis weight and other factors. Vital status information was obtained from the National Death Index through December 2005. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models and adjusted for prediagnosis weight, age, stage, smoking, physical activity, and other important covariates.

The authors investigated secular trends in age at menarche, age at menopause, and reproductive life span within a population-based cohort of US women. Study subjects were 22,774 women selected randomly as controls for a case-control study. Eligible controls were residents of Wisconsin, Massachusetts, or New Hampshire born between 1910 and 1969. Subjects completed telephone interviews in 1988-2001 and answered questions regarding reproductive and lifestyle factors. Birth cohorts were created using 5- and 10-year periods, and statistical comparisons were performed with analysis of variance. The mean age at menarche decreased by approximately 6 months for those born between 1910 and 1949 (13.1 vs. 12.7 years; p < 0.001), with a subsequent increase to 13.0 years among women born between 1960 and 1969 (p < 0.001). Among naturally menopausal women aged 60 or more years who reported never use of postmenopausal hormone therapy, the authors observed a 17-month increase in the mean age at menopause for those born between 1915 and 1939 (49.1 vs. 50.5 years; p = 0.001) after adjustment for potential confounders. They also observed an increase in the average number of reproductive years (subtracting age at menarche from age at natural menopause), from 36.1 years among women born between 1915 and 1919 to 37.7 years among the 1935-1939 cohort (p = 0.0001). These findings have implications for women's lifetime exposure to circulating endogenous hormones.

A B S T R A C T PurposeContralateral breast cancer (CBC) is the most frequent new malignancy among women diagnosed with a first breast cancer. Although temporal trends for first breast cancers have been well studied, trends for CBC are not so well established. Patients and MethodsWe examined temporal trends in CBC incidence using US Surveillance, Epidemiology, and End Results database (1975 to 2006). Data were stratified by estrogen receptor (ER) status of the first breast cancer for the available time period (1990ϩ). We estimated the annual percent change (EAPC) in CBC rates using Poisson regression models adjusted for the age at and time since first breast cancer diagnosis. ResultsBefore 1985, CBC incidence rates were stable (EAPC, 0.27% per year; 95% CI, Ϫ0.4 to 0.9), after which they declined with an EAPC of Ϫ3.07% per year (95% CI, Ϫ3.5 to Ϫ2.7). From 1990 forward, the declines were restricted to CBC after an ER-positive cancer (EAPC, Ϫ3.18%; 95% CI, Ϫ4.2 to Ϫ2.2) with no clear decreases after an ER-negative cancer. Estimated current age-specific CBC rates (per 100/year) after an ER-positive first cancer were: 0.45 for first cancers diagnosed before age 30 years and 0.25 to 0.37 for age 30 years or older. Rates after an ER-negative cancer were higher: 1.26 before age 30 years, 0.85 for age 30 to 35 years, and 0.45 to 0.65 for age 40 or older. ConclusionResults show a favorable decrease of 3% per year for CBC incidence in the United States since 1985. This overall trend was driven by declining CBC rates after an ER-positive cancer, possibly because of the widespread usage of adjuvant hormone therapies, after the results of the Nolvadex Adjuvant Trial Organisation were published in 1983, and/or other adjuvant treatments. Oncol 29:1564Oncol 29: -1569 J Clin

Background Greater body mass index (BMI), a measure of overall adiposity, is associated with higher risk of postmenopausal breast cancer. The role of central adiposity, often measured by waist circumference, is less well understood especially among premenopausal women. We aimed to examine multiple measures of adiposity in relation to breast cancer in a prospective cohort study. Methods 50,884 Sister Study cohort participants ages 35–74 were enrolled from 2003–2009. Inclusion criteria for the cohort included having a sister previously diagnosed with breast cancer. Trained study personnel measured height, weight, waist and hip circumference during a home visit and study participants completed a detailed questionnaire. Using Cox regression, we estimated multivariable hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk associated with adiposity measurements, considering tumor subtype and menopausal status. Results In total, 2,009 breast cancers were diagnosed during follow-up (mean=5.4 years). Weight, BMI, waist circumference and waist-hip-ratio were positively associated with overall breast cancer risk and HRs were greater among postmenopausal women, those with hormonally responsive tumors and non-current postmenopausal hormone users. In models that adjusted for BMI, waist circumference associations persisted among both postmenopausal women (81–88cm vs ≤80cm, HR=1.16, 95%CI 1.01, 1.35; >88cm vs ≤80cm, HR=1.30, 95% CI 1.10, 1.54) and premenopausal women (81–88cm vs ≤80cm, HR=1.56, 95%CI 1.19, 2.04; >88cm vs ≤80cm, HR=1.30, 95% CI 0.91, 1.87). Conclusions Findings from this large, prospective study with examiner-measured body size indicate that waist circumference is independently and positively associated with both premenopausal and postmenopausal breast cancer risk.

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.

Live births to AYA cancer survivors may have an increased risk of preterm birth and low birth weight, suggesting that additional surveillance of pregnancies in this population is warranted. Our findings may inform the reproductive counseling of female AYA cancer survivors.

Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (≥88 cm); elevated blood pressure (≥130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol-lowering medication use. During follow-up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m2 with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m2 and ≥1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR=1.26, 95% CI:1.01–1.56), as did women with a BMI ≥25 kg/m2 and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR=1.24, 95% CI:0.99–1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ≥88 cm, waist circumference ≥80 cm, and waist-hip ratio ≥0.85 of 1.58, 95% CI:1.02–2.46; 1.38, 95% CI:1.09–1.75; and 1.38, 95% CI:1.02–1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR=0.71, 95% CI:0.52–0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI.

This study suggests that family history of breast cancer as well as potentially modifiable characteristics including body weight, alcohol intake, and postmenopausal hormone use may be associated with risk of a second cancer diagnosis among breast cancer cases.