Background:The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures.Objective:The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer.Methods:A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors.Results:The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35–74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m2 (70%). Few (5%) reported any cancer prior to enrollment.Conclusions:The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923

The HER2 codon 655 polymorphism may be one of many low-penetrant genes that make a minor contribution to breast cancer, particularly in subgroups of women. Additional large studies, as well as data pooling, will be needed to estimate the contribution of such genes to breast cancer risk.

Introduction Much recent work has focused on hypotheses that very early life exposures influence adult cancer risk. For breast cancer it has been hypothesized that high in utero estrogen exposure may increase risk.

Dietary factors that contribute to chronic low‐grade metabolic acidosis have been linked to breast cancer risk, but to date no epidemiologic study has examined diet‐dependent acid load and breast cancer. We used data from 43,570 Sister Study participants who completed a validated food frequency questionnaire at enrollment (2003–2009) and satisfied eligibility criteria. The Potential Renal Acid Load (PRAL) score was used to estimate diet‐dependent acid load. Higher scores reflect greater consumption of protein and phosphorus, and lower consumption of potassium, calcium and magnesium. The association between PRAL and breast cancer was evaluated using multivariable Cox proportional hazards regression. We identified 1,614 invasive breast cancers diagnosed at least 1 year after enrollment (mean follow‐up, 7.6 years). The highest PRAL quartile, reflecting greater acid‐forming potential, was associated with increased risk of breast cancer (HRhighest vs. lowest quartile: 1.21 [95% CI, 1.04–1.41], ptrend = 0.04). The association was more pronounced for estrogen receptor (ER)‐negative (HRhighest vs. lowest quartile: 1.67 [95% CI, 1.07–2.61], ptrend = 0.03) and triple‐negative breast cancer (HRhighest vs. lowest quartile: 2.20 [95% CI, 1.23–3.95], ptrend = 0.02). Negative PRAL scores, representing consumption of alkaline diets, were associated with decreased risk of ER‐negative and triple‐negative breast cancer, compared to a PRAL score of 0 representing neutral pH. Higher diet‐dependent acid load may be a risk factor for breast cancer while alkaline diets may be protective. Since PRAL scores are positively correlated with meat consumption and negatively correlated with fruit and vegetable intake, results also suggest that diets high in fruits and vegetables and low in meat may be protective against hormone receptor negative breast cancer.

Introduction Chemotherapy for breast cancer has been associated with cognitive problems; however, the impact of adjuvant hormone therapy is less clear. No studies have explored provider discussions about cognitive concerns or factors associated with neurocognitive treatment. This study examined cognitive problems, factors associated with having a provider discussion, and receipt of neurocognitive treatment. Methods Female breast cancer survivors (N=2,537) from the Sister Study and the Two Sister Study who were at least 1 year post-treatment were surveyed in 2012 about their cancer therapies (confirmed by medical records), cognitive concerns, related provider discussions, and neurocognitive treatment. A total of 2,296 women were included in the current 2014 analysis. Extensive covariate information was also ascertained for predictive multivariate models. Results The prevalence of self-reported cognitive problems after treatment was 60%. Of those reporting cognitive problems, only 37% had discussed those concerns with a provider and 15% had been treated for cognitive symptoms. The odds of reported cognitive concerns that started during and after treatment were elevated for those who received only hormone therapy and no chemotherapy (OR=1.64, 95% CI=1.15, 2.33), chemotherapy and no hormone therapy (OR=5.63, 95% CI=3.52, 9.00), or both (OR=6.33, 95% CI=4.21, 9.54) compared with those reporting neither treatment. Conclusions The high prevalence of cognitive concerns underscores the importance of monitoring breast cancer survivors for potential neurocognitive effects of hormone and chemotherapy, discussions with survivors about those concerns, and treatment referrals. Monitoring changes over time can help to evaluate both psychosocial and neurocognitive care provided for survivors.