Breast Cancer-Related Employment Disruption and Financial Hardship in the Sister Study.

Background: More than one-half of breast cancer cases are diagnosed among women aged younger than 62 years, which may result in employment challenges. This study examined whether cancer-related employment disruption was associated with increased financial hardship in a national US study of women with breast cancer. Methods: Women with breast cancer who were enrolled in the Sister or Two Sister Studies completed a survivorship survey in 2012. Employment disruption was defined as stopping work completely or working fewer hours after diagnosis. Financial hardship was defined as: 1) experiencing financial problems paying for cancer care, 2) borrowing money or incurring debt, or 3) filing for bankruptcy because of cancer. Prevalence ratios and 95% confidence intervals for the association between employment disruption and financial hardship were estimated using multivariable Poisson regression with robust variance. Results: We analyzed data from women employed at diagnosis (n = 1628). Women were a median age of 48 years at diagnosis and 5.6 years from diagnosis at survey completion. Overall, 27.3% of women reported employment disruption (15.4% stopped working; 11.9% reduced hours), and 21.0% experienced financial hardship (16.0% had difficulty paying for care; 12.6% borrowed money or incurred debt; 1.8% filed for bankruptcy). In adjusted analysis, employment disruption was associated with nearly twice the prevalence of financial hardship (prevalence ratio = 1.93, 95% confidence interval = 1.58 to 2.35). Conclusions: Women experiencing employment disruptions after breast cancer may be more vulnerable to financial hardship. Findings highlight the need to target risk factors for employment disruption, facilitate return to work or ongoing employment, and mitigate financial consequences after cancer.

Dietary inflammatory potential, oxidative balance score, and risk of breast cancer: Findings from the Sister Study.

Diet, inflammation, and oxidative stress may be important in breast carcinogenesis, but evidence on the role of the inflammatory and prooxidative potential of dietary patterns is limited. Energy adjusted-Dietary Inflammatory Index (E-DII™) and dietary oxidative balance score (D-OBS) were calculated for 43 563 Sister Study cohort participants who completed a Block 1998 food frequency questionnaire at enrollment in 2003-2009 and satisfied eligibility criteria. D-OBS was validated using measured F2 -isoprostanes and metabolites. High E-DII score and low D-OBS represent a more proinflammatory and prooxidant diet, respectively, and associations of quartiles of each index with breast cancer (BC) risk were estimated using multivariable Cox proportional hazards regression. There were 2619 BCs diagnosed at least 1 year after enrollment (mean follow-up 8.4 years). There was no overall association between E-DII and BC risk, whereas there was a suggestive inverse association for the highest vs lowest quartile of D-OBS (HR 0.92 [95% CI, 0.81-1.03]). The highest quartile of E-DII was associated with risk of triple-negative BC (HR 1.53 [95% CI, 0.99-2.35]). When the two indices were combined, a proinflammatory/prooxidant diet (highest tertile of E-DII and lowest tertile of D-OBS) was associated with increased risk for all BC (HR 1.13 [95% CI, 1.00-1.27]) and for triple-negative BC (1.72 [95% CI, 1.10-2.70]), compared to an antiinflammatory/antioxidant diet (lowest tertile of E-DII and highest tertile of D-OBS). Diets with increased inflammatory potential and reduced oxidative balance were positively associated with overall and triple-negative BC.

Employment After Breast Cancer Diagnosis and Treatment Among Women in the Sister and the Two Sister Studies.

Purpose Women undergoing diagnosis and treatment for breast cancer may face challenges in employment. We investigated the impact of demographic, clinical, workplace, and psychosocial characteristics on loss of employment after a breast cancer diagnosis and treatment. We further describe changes in work status and work environment for cancer survivors who sustain employment. Methods We analyzed responses from a survey of breast cancer survivors from the Sister Study and the Two Sister Study cohorts who reported being employed at the time of their breast cancer diagnosis and who reported employment status (lost vs. sustained employment) at the time of survey administration. Multivariate logistic regression was used to identify the effects of lymphedema, neuropathy, problems with memory or attention, social support, health insurance, and sick leave on lost employment, adjusting for demographic characteristics, cancer stage, treatment, and general health. Results Of the 1675 respondents who reported being employed at the time of diagnosis, 83.5% reported being 'currently' employed at the time of the survey. Older age, peripheral neuropathy, lack of sick leave, late stage at diagnosis, a recurrence or a new cancer, problems with memory or attention, and poor general health were significantly associated with lost employment. Conclusions The long-term effects of breast cancer treatment and workplace provisions for leave and accommodation may have a substantial effect on women's ability to sustain employment. The findings from this study highlight challenges reported by cancer survivors that may inform clinical and occupational interventions to support survivors' return to work.

Health-related quality of life outcomes among breast cancer survivors.

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.

Fertility-related experiences after breast cancer diagnosis in the Sister and Two Sister Studies.

BACKGROUND: Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability. METHODS: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling. RESULTS: Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35 years vs ≥40 years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%). CONCLUSIONS: Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education.

Factors associated with breast MRI use among women with a family history of breast cancer.

Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85-17.06), 2.48 (95% CI, 2.27-2.71), and 2.50 (95% CI, 2.09-2.99) for positive BRCA1/2 test, lifetime breast cancer risk ≥ 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82-2.75) and OR = 1.76 (95% CI, 1.52-2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications.

Communicating with Daughters About Familial Risk of Breast Cancer: Individual, Family, and Provider Influences on Women's Knowledge of Cancer Risk.

INTRODUCTION: Women facing complex and uncertain situations such as cancer in their families may seek information from a variety of sources to gain knowledge about cancer risk and reduce uncertainty. We describe and assess the relative importance of information sources about familial breast cancer at the individual, family, and healthcare provider levels influencing women's reporting they had enough information to speak with daughters about breast cancer. This outcome we refer to as being informed about breast cancer. MATERIALS AND METHODS: Sister Study participants, a cohort of women with a family history of breast cancer, were surveyed on family cancer history, family communication, social support, and interactions with healthcare providers (n = 11,766). Adjusted percentages and 95% confidence intervals for being informed about breast cancer versus not being informed were computed for individual-, family-, and provider-level characteristics in three steps using multivariate logistic regression models. RESULTS: We found 65% of women reported being informed about breast cancer while 35% did not. Having a trusted person with whom to discuss cancer concerns, having a lower versus higher perceived risk of breast cancer, having undergone genetic counseling, and being satisfied with physician discussions about breast cancer in their families were predictors of being informed about breast cancer. CONCLUSIONS: Although acquiring objective risk information, such as through genetic counseling, may contribute to a basic level of understanding, communication with providers and within other trusted relationships appears to be an essential component in women's reporting they had all the information they need to talk with their daughters about breast cancer.

Validity of self-reported breast cancer characteristics in a nationwide cohort of women with a family history of breast cancer.

BACKGROUND: Women 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. METHODS: We 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. RESULTS: Medical 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. CONCLUSIONS: Accuracy 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.

Age- and treatment-related associations with health behavior change among breast cancer survivors.

OBJECTIVE: The aim of this study was to identify demographic and treatment-related factors associated with health-promoting behavior changes after a breast cancer diagnosis. Changes in health behaviors were also evaluated according to weight, exercise, diet and alcohol consumption patterns before breast cancer diagnosis. MATERIALS AND METHODS: We examined self-reported behavior changes among 1415 women diagnosed with breast cancer in the NIEHS Sister Study cohort. Women reported changes in exercising, eating healthy foods, maintaining a healthy body weight, drinking alcohol, smoking, getting enough sleep, spending time with family and friends, and participating in breast cancer awareness events. RESULTS: On average, women were 3.7 years from their breast cancer diagnosis. Overall, 20-36% reported positive changes in exercise, eating healthy foods, maintaining a healthy weight, or alcohol consumption. However, 17% exercised less. With each 5-year increase in diagnosis age, women were 11-16% less likely to report positive change in each of these behaviors (OR = 0.84-0.89; p < 0.05), except alcohol consumption (OR = 0.97; CI: 0.81, 1.17). Women who underwent chemotherapy were more likely to report eating more healthy foods (OR = 1.47; 95% CI 1.16-1.86), drinking less alcohol (OR = 2.01; 95% CI: 1.01, 4.06), and sleeping enough (OR = 1.41; 95% CI: 1.04, 1.91). The majority of women (50-84%) reported no change in exercise, eating healthy foods, efforts to maintain a healthy weight, alcohol consumption, sleep patterns, or time spent with family or friends. CONCLUSIONS: Many women reported no change in cancer survivorship guideline-supported behaviors after diagnosis. Positive changes were more common among younger women or those who underwent chemotherapy.

The Sister Study Cohort: Baseline Methods and Participant Characteristics.

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.

Post-treatment Neurocognition and Psychosocial Care Among Breast Cancer Survivors.

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.

The case-only independence assumption: associations between genetic polymorphisms and smoking among controls in two population-based studies.

The independence assumption for a case-only analysis of statistical interaction, i. e. that genetic (G) and environmental exposures (E) are not associated in the source population, is often checked in surrogate populations. Few studies have examined G-E association in empirical data, particularly in controls from population-based studies, the type of controls expected to provide the most valid surrogate estimates of G-E association. We used controls from two population-based case-control studies to evaluate G-E independence for 43 selected genetic polymorphisms and smoking behavior. The odds ratio (OR(z)) was used to estimate G-E association and, therefore, the magnitude of bias introduced into the case-only odds ratio (COR). Odds ratios of moderate magnitude [mmOR(z)], defined as OR(z)≤0.7 or OR(z)≥1.4, were found at least one of the six smoking measures (ever, former, current, cig/day, years smoked, pack-years) for 45% and 59% of the SNPs examined in the control groups of two independently conducted North Carolina studies, respectively. Consequently, case-only estimates of G-E interaction in the context of a multiplicative benchmark would be biased for these SNPs and smoking measures. MmOR(z)s were found more often for smoking amount than smoking status. We recommend that a stand-alone case-only study should only be conducted when G-E independence can be verified for each polymorphism and exposure metric with population-specific data. Our results suggest that OR(z) is specific to each underlying population rather than an estimate of a 'universal' OR(z) for that SNP and smoking measure. Further, misspecification of smoking is likely to introduce bias into the COR.

Smoking and selected DNA repair gene polymorphisms in controls: systematic review and meta-analysis.

BACKGROUND: When the case-only study design is used to estimate statistical interaction between genetic (G) and environmental (E) exposures, G and E must be independent in the underlying population, or the case-only estimate of interaction (COR) will be biased. Few studies have examined the occurrence of G-E association in published control group data. METHODS: To examine the assumption of G-E independence in empirical data, we conducted a systematic review and meta-analysis of G-E associations in controls for frequently investigated DNA repair genes (XRCC1 Arg399Gln, Arg194Trp, or Arg280His, XPD Lys751Gln, and Asp312Asn, and XRCC3 Thr241Met), and smoking (ever/never smoking, current/not current smoker, smoking duration, smoking intensity, and pack-years). RESULTS: Across the 55 included studies, single nucleotide polymorphisms SNP-smoking associations in controls (OR(z)) were not reliably at the null value of 1.0 for any SNP-smoking combinations. Two G-E combinations were too heterogeneous for summary estimates: XRCC1 399 and ever-never smoking (N = 21), and XPD 751 and pack-years (N = 12). OR(z) ranges for these combinations were: [OR(z) (95% confidence interval (CI)] 0.7 (0.4, 1.2)-1.9 (1.2, 2.8) and 0.8 (0.5, 1.3)-2.3 (0.8, 6.1), respectively). Estimates for studies considered homogeneous (Cochran's Q P-value <0.10) varied 2- to 5-fold. No study characteristics were identified that could explain heterogeneity. CONCLUSIONS: We recommend the independence assumption be evaluated in the population underlying any potential case-only study, rather than in a proxy control group(s) or pooled controls. IMPACT: These results suggest that G-E association in controls may be population-specific. Increased access to control data would improve evaluation of the independence assumption.

Birthweight, parental age, birth order and breast cancer risk in African-American and white women: a population-based case-control study.

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. METHODS: We used data from the Carolina Breast Cancer Study, a population-based case-control study of incident breast cancer in North Carolina, to examine associations for three possible surrogates of high prenatal estrogen exposure: weight at birth, maternal age, and birth order. We also examined paternal age. Birthweight analyses were conducted for white and African-American women born in North Carolina on or after 1949 (196 cases, 167 controls). Maternal age was analyzed for US born participants younger than 49 years of age (280 cases, 236 controls). RESULTS: There was a weak inverse association between birthweight in the highest tertile and breast cancer overall (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.4-1.2), although associations differed by race (OR 0.5, 95% CI 0.2-1.0, and OR 1.0, 95% CI 0.5-2.1 for African-American and white women, respectively). For maternal age there was an approximately threefold increase in risk in women whose mothers were older than 22 years of age, relative to 19-22 years of age, when the women were born. After adjustment for maternal age, older paternal age increased risk in the oldest and youngest age categories (relative to 23-27 years of age at the woman's birth: OR 1.6, 95% CI 0.8-3.1 for age 15-22 years; OR 1.2, 95% CI 0.7-2.2 for age 28-34 years; and OR 1.5, 95% CI 0.7-3.2 for age 35-56 years). There was no association with older paternal age for white women alone. After adjustment for maternal age (265 cases, 224 controls), a birth order of fifth or higher relative to first had an inverse association with breast cancer for women younger than 49 years old (OR 0.6, 95% CI 0.3-1.3). CONCLUSION: Although the CIs are wide, these results lend support to the possibility that the prenatal period is important for subsequent breast cancer risk, but they do not support the estrogen hypothesis as a unifying theory for the influence of this period.