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.

Background Contralateral prophylactic mastectomy (CPM) rates have been increasing in the U.S. Though some studies have reported high overall satisfaction among women who undergo CPM, it is unclear how long-term satisfaction differs from that of women who undergo unilateral mastectomy (UM). Furthermore, few studies have assessed whether the effects of CPM on body image differ from those of breast conserving surgery (BCS) or UM. Methods We analyzed responses from a survey of women with both a personal and family history of breast cancer who were enrolled in the Sister Study (n=1176). Among women who underwent mastectomy, satisfaction with mastectomy decision and reconstruction was compared between women who underwent CPM and UM. We also evaluated responses on 5 items related to body image according to surgery type (BCS, UM without reconstruction, CPM without reconstruction, UM with reconstruction, and CPM with reconstruction). Results Participants were, on average, 60.8 years old at diagnosis (SD=8.7) and 3.6 years post-diagnosis at the time of survey (SD=1.7). BCS was the most common surgical treatment reported (63%), followed by CPM (22%) and UM (15%). Satisfaction with mastectomy decision was reported by 97% of women who underwent CPM and 89% of those who underwent UM. Compared to other surgery types, women who underwent CPM without reconstruction reported feeling more self-conscious, less feminine, less whole, and less satisfied with the appearance of their breasts. Body image was consistently highest among women who underwent BCS. Conclusions In our sample of women with both a personal and family history of breast cancer, most were highly satisfied with their mastectomy decision, including those who elected to undergo CPM. However, body image was lowest among women who underwent CPM without reconstruction. Our findings may inform decisions among women considering various courses of surgical treatment.

BackgroundWomen may have incomplete understanding of a breast cancer diagnosis, leading to inaccurate reporting in epidemiological studies. However, it is not feasible to obtain consent for medical records from all women participating in a study. Therefore, it is important to determine how well self-reported breast cancer characteristics correspond with what is found in medical records, but few studies have evaluated agreement of self-reported breast cancer characteristics with abstracted medical records.MethodsWe calculated the positive predictive value (PPV) of self-reports compared to medical records and explored whether participant characteristics may have influenced reporting accuracy. We analyzed data from 2518 reported breast cancer cases from the Sister Study, a large nationwide cohort of women with a family history of breast cancer.ResultsMedical records or pathology reports were obtained for 2066 of 2518 (82%) women who reported incident breast cancer. Breast cancer was confirmed for over 99% (n = 2054) of women with medical records. Confirmation rates were high for invasive, ductal, hormone receptor positive, and HER2 negative breast cancers, with little variation by race/ethnicity or age. Self-reported in situ breast cancer had a lower PPV (64.2%), with medical records showing invasive breast cancer instead, especially for older and Hispanic women. Hormone receptor (ER and PR) negative and HER2 positive self-reports had lower PPVs (83.0%, 71.6%, and 66.1% respectively). Hispanic women and women ages 65 or older at diagnosis were less able to accurately report breast cancer stage, excluding stage I.ConclusionsAccuracy of reporting overall breast cancer and common subtypes is high. Despite having a family history of breast cancer and voluntarily enrolling in a study evaluating breast cancer risk factors, participants may have greater difficulty distinguishing between in situ and invasive breast cancer and may less accurately report other less common subtypes. Discrepancies may reflect women’s poor understanding of information conveyed by health care providers or lack of consistent terminology used to describe subtypes.

Background Data from a nationwide sample of US breast cancer survivors were used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health‐related quality of life (HRQOL). Associations between postdiagnosis HRQOL and mortality were then evaluated. Methods The authors identified female breast cancer survivors (n = 2453) from the Sister Study or Two Sister Study who were at least 1 year from breast cancer diagnosis and who had responded to a survivorship survey in 2012. HRQOL was assessed with the Patient‐Reported Outcomes Measurement Information System (PROMIS) Global 10 measures. Multivariable linear regression was used to assess predictors associated with HRQOL. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HRQOL and all‐cause mortality. Results HRQOL, assessed an average of 4.9 years after the cancer diagnosis (standard deviation of 1.9 years), was negatively associated with a higher cancer stage at diagnosis; a higher comorbidity score at the survey; experience of surgical complications; dissatisfaction with breast surgery; and experience of any recent recurrence, metastasis, or secondary malignancy. Since the completion of the survey, there were 85 deaths (3.5%) during a mean follow‐up of 4 years (standard deviation of 0.5 years). In multivariate models, decreases in PROMIS physical T scores and mental T scores were associated with increased mortality (HR for physical T scores, 1.08; 95% CI, 1.05‐1.11; HR for mental T scores, 1.03; 95% CI, 1.01‐1.06). Conclusions Prognostic and cancer treatment–related factors affect HRQOL in breast cancer survivors and may inform targeted survivorship care. PROMIS global health measures may offer additional insights into patients' well‐being and mortality risk. Lay Summary Findings from a study suggest that prognostic and cancer treatment–related factors affect health‐related quality of life (HRQOL) in breast cancer survivors and that poor HRQOL may increase the mortality risk. The evaluation of HRQOL is important because it may hold potential as a tool for optimizing survivorship care.