A pooled case-only analysis of obesity and breast cancer subtype among Black women in the southeastern United States.

PURPOSE: To evaluate the association between obesity and the relative prevalence of tumor subtypes among Black women with breast cancer (BC). METHODS: We conducted a pooled case-only analysis of 1,793 Black women with invasive BC recruited through three existing studies in the southeastern US. Multivariable case-only polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between obesity, measured by pre-diagnostic body mass index (BMI), and human epidermal growth factor receptor 2 + (HER2 +) and triple negative BC (TNBC) subtype relative to hormone receptor (HR) + /HER2- status (referent). RESULTS: Among 359 premenopausal women, 55.4% of cases were HR + /HER2 -, 20.1% were HER2 + , and 24.5% were TNBC; corresponding percentages among 1,434 postmenopausal women were 59.3%, 17.0%, and 23.6%. Approximately, 50-60% of both pre- and postmenopausal women were obese (BMI > 30 kg/m2), regardless of BC subtype. We did not observe a significant association between obesity and BC subtype. Among postmenopausal women, class I obesity (BMI 35 + kg/m2) was not associated with the development of HER2 + BC (OR 0.69; 95% CI 0.42-1.14) or TNBC (OR 0.93; 95% CI 0.60-1.45) relative to HR + /HER2- tumors. Corresponding estimates among premenopausal women were 1.03 (95% CI 0.43-2.48) and 1.13 (95% CI 0.48-2.64). CONCLUSION: In this large study of Black women with BC, there was no evidence of heterogeneity of BMI by BC subtype.

Evaluating breast cancer predisposition genes in women of African ancestry.

PURPOSE: Studies conducted primarily among European ancestry women reported 12 breast cancer predisposition genes. However, etiologic roles of these genes in breast cancer among African ancestry women have been less well-investigated. METHODS: We conducted a case-control study in African American women, which included 1117 breast cancer cases and 2169 cancer-free controls, and a pooled analysis, which included 7096 cases and 8040 controls of African descent. Odds ratios of associations with breast cancer risk were estimated. RESULTS: Using sequence data, we identified 61 pathogenic variants in 12 breast cancer predisposition genes, including 11 pathogenic variants not yet reported in previous studies. Pooled analysis showed statistically significant associations of breast cancer risk with pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, TP53, NF1, RAD51C, and RAD51D (all P < .05). The associations with BRCA1, PALB2, and RAD51D were stronger for estrogen receptor (ER)-negative than for ER-positive breast cancer (P heterogeneity < .05), whereas the association with CHEK2 was stronger for ER-positive than for ER-negative breast cancer. CONCLUSION: Our study confirmed previously identified associations of breast cancer risk with BRCA1, BRCA2, PALB2, ATM, TP53, NF1, and CHEK2 and provided new evidence to extend the associations of breast cancer risk with RAD51C and RAD51D, which was identified previously in European ancestry populations, to African ancestry women.

Discovery of structural deletions in breast cancer predisposition genes using whole genome sequencing data from > 2000 women of African-ancestry.

Single germline nucleotide pathogenic variants have been identified in 12 breast cancer predisposition genes, but structural deletions in these genes remain poorly characterized. We conducted in-depth whole genome sequencing (WGS) in genomic DNA samples obtained from 1340 invasive breast cancer cases and 675 controls of African ancestry. We identified 25 deletions in the intragenic regions of ten established breast cancer predisposition genes based on a consensus call from six state-of-the-art SV callers. Overall, no significant case-control difference was found in the frequency of these deletions. However, 1.0% of cases and 0.3% of controls carried any of the eight putative protein-truncating rare deletions located in BRCA1, BRCA2, CDH1, TP53, NF1, RAD51D, RAD51C and CHEK2, resulting in an odds ratio (OR) of 3.29 (95% CI 0.74-30.16). We also identified a low-frequency deletion in NF1 associated with breast cancer risk (OR 1.93, 95% CI 1.14-3.42). In addition, we detected 56 deletions, including six putative protein-truncating deletions, in suspected breast predisposition genes. This is the first large study to systematically search for structural deletions in breast cancer predisposition genes. Many of the deletions, particularly those resulting in protein truncations, are likely to be pathogenic. Results from this study, if confirmed in future large-scale studies, could have significant implications for genetic testing for this common cancer.

Feasibility of precision smoking treatment in a low-income community setting: results of a pilot randomized controlled trial in The Southern Community Cohort Study.

BACKGROUND: The feasibility of precision smoking treatment in socioeconomically disadvantaged communities has not been studied. METHODS: Participants in the Southern Community Cohort Study who smoked daily were invited to join a pilot randomized controlled trial of three smoking cessation interventions: guideline-based care (GBC), GBC plus nicotine metabolism-informed care (MIC), and GBC plus counseling guided by a polygenic risk score (PRS) for lung cancer. Feasibility was assessed by rates of study enrollment, engagement, and retention, targeting > 70% for each. Using logistic regression, we also assessed whether feasibility varied by age, sex, race, income, education, and attitudes toward precision smoking treatment. RESULTS: Of 92 eligible individuals (79.3% Black; 68.2% with household income < $15,000), 67 (72.8%; 95% CI 63.0-80.9%) enrolled and were randomized. Of these, 58 (86.6%; 95% CI 76.4-92.8%) engaged with the intervention, and of these engaged participants, 43 (74.1%; 95% CI 61.6-83.7%) were retained at 6-month follow-up. Conditional on enrollment, older age was associated with lower engagement (OR 0.83, 95% CI 0.73-0.95, p = 0.008). Conditional on engagement, retention was significantly lower in the PRS arm than in the GBC arm (OR 0.18, 95% CI 0.03-1.00, p = 0.050). No other selection effects were observed. CONCLUSIONS: Genetically informed precision smoking cessation interventions are feasible in socioeconomically disadvantaged communities, exhibiting high enrollment, engagement, and retention irrespective of race, sex, income, education, or attitudes toward precision smoking treatment. Future smoking cessation interventions in this population should take steps to engage older people and to sustain participation in interventions that include genetic risk counseling. TRIAL REGISTRATION: ClinicalTrials.gov No. NCT03521141, Registered 27 April 2018, https://www. CLINICALTRIALS: gov/study/NCT03521141.

Dispositional optimism and optimistic bias: Associations with cessation motivation, confidence, and attitudes.

OBJECTIVE: To test whether 2 conceptually overlapping constructs, dispositional optimism (generalized positive expectations) and optimistic bias (inaccurately low risk perceptions), may have different implications for smoking treatment engagement. METHOD: Predominantly Black, low-income Southern Community Cohort study smokers (n = 880) self-reported dispositional optimism and pessimism (Life Orientation Test-Revised subscales: 0 = neutral, 12 = high optimism/pessimism), comparative lung cancer risk (Low/Average/High), and information to calculate objective lung cancer risk (Low/Med/High). Perceived risk was categorized as accurate (perceived = objective), optimistically-biased (perceived < objective), or pessimistically-biased (perceived > objective). One-way ANOVAs tested associations between dispositional optimism/pessimism and perceived risk accuracy. Multivariable logistic regressions tested independent associations of optimism/pessimism and perceived risk accuracy with cessation motivation (Low/High), confidence (Low/High), and precision treatment attitudes (Favorable/Unfavorable), controlling for sociodemographics and nicotine dependence. RESULTS: Mean dispositional optimism/pessimism scores were 8.41 (SD = 2.59) and 5.65 (SD = 3.02), respectively. Perceived lung cancer risk was 38% accurate, 27% optimistically-biased, and 35% pessimistically-biased. Accuracy was unrelated to dispositional optimism (F(2, 641) = 1.23, p = .29), though optimistically-biased (vs. pessimistically-biased) smokers had higher dispositional pessimism (F(2, 628) = 3.17, p = .043). Dispositional optimism was associated with higher confidence (Adjusted odds ratio [AOR] = 1.71, 95% CI [1.42, 2.06], p < .001) and favorable precision treatment attitudes (AOR = 1.66, 95% CI [1.37, 2.01], p < .001). Optimistically-biased (vs. accurate) risk perception was associated with lower motivation (AOR = .64, 95% CI [.42, .98], p = .041) and less favorable precision treatment attitudes (AOR = .59, 95% CI [.38, .94], p = .029). CONCLUSIONS: Dispositional optimism and lung cancer risk perception accuracy were unrelated. Dispositional optimism was associated with favorable engagement-related outcomes and optimistically-biased risk perception with unfavorable outcomes, reinforcing the distinctiveness of these constructs and their implications for smoking treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Pooled Case-only Analysis of Reproductive Risk Factors and Breast Cancer Subtype Among Black Women in the Southeastern United States.

BACKGROUND: We investigated the association between reproductive risk factors and breast cancer subtype in Black women. On the basis of the previous literature, we hypothesized that the relative prevalence of specific breast cancer subtypes might differ according to reproductive factors. METHODS: We conducted a pooled analysis of 2,188 (591 premenopausal, 1,597 postmenopausal) Black women with a primary diagnosis of breast cancer from four studies in the southeastern United States. Breast cancers were classified by clinical subtype. Case-only polytomous logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for HER2+ and triple-negative breast cancer (TNBC) status in relation to estrogen receptor-positive (ER+)/HER2- status (referent) for reproductive risk factors. RESULTS: Relative to women who had ER+/HER2- tumors, women who were age 19-24 years at first birth (OR, 1.78; 95% CI, 1.22-2.59) were more likely to have TNBC. Parous women were less likely to be diagnosed with HER2+ breast cancer and more likely to be diagnosed with TNBC relative to ER+/HER2- breast cancer. Postmenopausal parous women who breastfed were less likely to have TNBC [OR, 0.65 (95% CI, 0.43-0.99)]. CONCLUSIONS: This large pooled study of Black women with breast cancer revealed etiologic heterogeneity among breast cancer subtypes. IMPACT: Black parous women who do not breastfeed are more likely to be diagnosed with TNBC, which has a worse prognosis, than with ER+/HER2- breast cancer.

Improving Community Advisory Board Engagement in Precision Medicine Research to Reduce Health Disparities.

Community Advisory Boards (CABs) are used in efforts to reduce health disparities; however, there is little documentation in the literature regarding their use in precision medicine research. In this case study, an academic-CAB partnership developed a questionnaire and patient educational materials for two precision smoking cessation interventions that involved use of genetic or genetically-informed information. The community-engaged research (CEnR) literature provided a framework for enhancing benefits to CAB members involved in developing research documents for use with a low-income, ethnically diverse population of smokers.The academic partners integrated three CEnR strategies: 1) in-meeting statements acknowledging their desire to learn from community partners, 2) in-meeting written feedback to and from community partners, and 3) a survey to obtain CAB member feedback post-meetings. Strategies 1 and 2 yielded modifications to pertinent study materials, as well as suggestions for improving meeting operations that were then adopted, as appropriate, by the academic partners. The survey indicated that CAB members valued the meeting procedure changes which appeared to have contributed to improvements in attendance and satisfaction with the meetings. Further operationalization of relevant partnership constructs and development of tools for measuring these aspects of community-academic partnerships is warranted to support community engagement in precision medicine research studies.

Attitudes toward Precision Treatment of Smoking in the Southern Community Cohort Study.

BACKGROUND: Precision interventions using biological data may enhance smoking treatment, yet are understudied among smokers who are disproportionately burdened by smoking-related disease. METHODS: We surveyed smokers in the NCI-sponsored Southern Community Cohort Study, consisting primarily of African-American, low-income adults. Seven items assessed attitudes toward aspects of precision smoking treatment, from undergoing tests to acting on results. Items were dichotomized as favorable (5 = strongly agree/4 = agree) versus less favorable (1 = strongly disagree/2 = disagree/3 = neutral); a summary score reflecting generalized attitudes was also computed. Multivariable logistic regression tested independent associations of motivation (precontemplation, contemplation, and preparation) and confidence in quitting (low, medium, and high) with generalized attitudes, controlling for sociodemographic factors and nicotine dependence. RESULTS: More than 70% of respondents endorsed favorable generalized attitudes toward precision medicine, with individual item favorability ranging from 64% to 83%. Smokers holding favorable generalized attitudes reported higher income and education (P < 0.05). Predicted probabilities of favorable generalized attitudes ranged from 63% to 75% across motivation levels [contemplation vs. precontemplation: adjusted odds ratio (AOR) = 2.10, 95% confidence interval (CI), 1.36-3.25, P = 0.001; preparation vs. precontemplation: AOR = 1.83, 95% CI, 1.20-2.78, P = 0.005; contemplation vs. preparation: AOR = 1.15, 95% CI, 0.75-1.77, P = 0.52] and from 59% to 78% across confidence (medium vs. low: AOR = 1.91, 95% CI, 1.19-3.07, P = 0.007; high vs. low: AOR = 2.62, 95% CI, 1.68-4.10, P < 0.001; medium vs. high: AOR = 0.73, 95% CI, 0.48-1.11, P = 0.14). CONCLUSIONS: Among disproportionately burdened community smokers, most hold favorable attitudes toward precision smoking treatment. Individuals with lower motivation and confidence to quit may benefit from additional intervention to engage with precision smoking treatment. IMPACT: Predominantly favorable attitudes toward precision smoking treatment suggest promise for future research testing their effectiveness and implementation.

Frequency and types of partner violence among Mexican American college women.

OBJECTIVE AND PARTICIPANTS: The authors studied the prevalence of partner violence, by type, among Mexican American college women aged 18 to 35 years (N = 149; response rate = 85%). RESULTS: Twelve percent of women who reported a dating partner in the past year were physically or sexually assaulted, 12.1% were stalked, and 9.1% scored as psychologically abused. Among those experiencing partner violence, almost half experienced stalking and 89% reported psychological abuse. Few women (25%) who experienced physical violence believed violence was a problem in their relationship. CONCLUSIONS: Partner violence was prevalent in this population, and participants experienced many forms of violence. Because few women experiencing physical violence report that violence is a problem in their relationship, interventions must address perceptions of violence and its impact on women's mental and physical health in college populations.

Partner violence screening in rural health care clinics.

OBJECTIVES: We sought to determine the frequency of intimate partner violence by type in a large, clinic-based, nurse-administered screening and services intervention project. METHODS: A brief intimate partner violence screen, which included items to measure sexual and physical assaults and psychological battering (using the Women's Experience With Battering scale) was administered to consenting women receiving care at 1 of 8 rural clinics in South Carolina. RESULTS: Between April 2002 and August 2005, 4945 eligible women were offered intimate partner violence screening, to which 3664 (74.1%) consented. Prevalence of intimate partner violence in a current (ongoing) relationship was 13.3%, and 939 women (25.6%) had experienced intimate partner violence at some point in the past 5 years. Of those ever experiencing intimate partner violence, the majority (65.6%) experienced both assaults and psychological battering; 10.1% experienced assault only, and 24.3% experienced psychological battering only. Most women (85.5%) currently experiencing both psychological battering and assaults stated that violence was a problem in their current relationship. CONCLUSIONS: The intimate partner violence screening technique we used was feasible to implement, acceptable to women seeking health care at the targeted clinics, and indicated a high proportion of women reporting intimate partner violence in the past 5 years, with a majority of those women stating that such violence was a problem in their relationships. These findings demonstrated the viability of the screening technique, which supports the growing importance of implementing intimate partner violence screenings in clinical settings in order to reduce the prevalence of violence in intimate relationships.

Serum leptin concentration, adiposity, and body fat distribution in Mexican-Americans.

BACKGROUND: Leptin is strongly associated with adiposity and few studies have investigated its role in Mexican-Americans. The aims of this study were to examine the association of serum leptin concentration with adiposity and body fat distribution in Mexican-Americans and to develop a predictive model of serum leptin concentration for this ethnic group. METHODS: Three hundred fifty-two college students (242 women, 110 men; age 18-30 years) were evaluated in this cross-sectional study. Body fat content was assessed using bioelectrical impedance analysis. Correlation between serum leptin levels and several markers of adiposity and body fat distribution were examined in both men and women. Multiple regression analysis was performed to create the predictive model. RESULTS: Women had higher serum leptin concentrations than men for the same levels of adiposity. After controlling for gender and body fat, only fat mass (FM) expressed in kg, was significantly correlated with serum leptin concentration in men (partial rho = 0.811, p <0.001), whereas body mass index (BMI), hip circumference (HC), and FM expressed in kg, were significantly correlated with serum leptin concentration in women (partial rho = 0.214, p <0.001; partial rho = 0.201, p <0.01; and partial rho = 0.818, p <0.001, respectively). Percent body fat (PBF) was the only significant predictor of serum leptin concentration among men, explaining 42% of the variance in serum leptin concentration. In addition to PBF, waist circumference (WC) and HC were significant predictors of serum leptin concentration among women explaining 65% of the variance in serum leptin concentration. CONCLUSIONS: Serum leptin concentration is a function of adiposity as determined by PBF in both Mexican-American men and women. HC and WC are associated with serum leptin concentration in Mexican-American women but not in men. BMI alone should not be used in evaluating the association of serum leptin concentration with body fatness in Mexican-Americans.

Time from Screening Mammography to Biopsy and from Biopsy to Breast Cancer Treatment among Black and White, Women Medicare Beneficiaries Not Participating in a Health Maintenance Organization.

PURPOSE: There is a breast cancer mortality gap adversely affecting Black women in the United States. This study assessed the relationship between number of days between abnormal mammogram, biopsy, and treatment among Medicare (Part B) beneficiaries ages 65 to 74 and 75 to 84 years, accounting for race and comorbidity. METHODS: A cohort of non-Hispanic Black and non-Hispanic White women residing in the continental United States and receiving no services from a health maintenance organization was randomly selected from the Center for Medicare and Medicaid Services denominator file. The cohort was followed from 2005 to 2008 using Center for Medicare and Medicaid Services claims data. The sample included 4,476 women (weighted n = 70,731) with a diagnosis of breast cancer. Cox proportional hazard modeling was used to identify predictors of waiting times. FINDINGS: Black women had a mean of 16.7 more days between biopsy and treatment (p < .001) and 15.7 more days from mammogram to treatment (p = .003) than White women. Median duration from abnormal mammogram to treatment exceeded National Quality Measures for Breast Centers medians regardless of race, age, or number of comorbidities (overall 43 days vs. the National Quality Measures for Breast Centers value of 28 days). CONCLUSIONS: Medical care delays may contribute, in part, to the widening breast cancer mortality gap between Black women and White women. Further study, with additional clinical and social information, is needed to broaden scientific understanding of racial determinants and assess the clinical significance of mammogram to treatment times among Medicare beneficiaries.

Physical partner violence and medicaid utilization and expenditures.

OBJECTIVES: Little research has addressed differences in health care expenditures among women who are currently experiencing intimate partner violence (IPV) compared with those who are not. The purpose of this work is to provide estimates of direct medical expenditure for physician, drug, and hospital utilization among Medicaid-eligible women who screened as currently experiencing IPV compared with those who are not currently experiencing IPV. METHODS: In this family practice-based cross-sectional study, women were screened for current IPV using a 15-item Index of Spouse Abuse-Physical (ISA-P) between 1997 and 1998. Consents were obtained from study subjects to review Medicaid expenditure and utilization data for the same time period. RESULTS: Mean physician, hospital, and total expenditures were higher for those women with higher IPV scores compared with those who scored as not currently experiencing IPV, after adjusting for confounders. Higher IPV scores were associated with a three-fold increased risk of having a total expenditure over $5,000 (95% confidence interval [CI] 1.3, 8.4). The mean total expenditure difference between the high IPV and no IPV groups was $1,064 (95% CI $623, $1506). The adjusted risk ratio for high IPV score and the log of total Medicaid expenditures was 2.3 (95% CI 1.2, 4.4). CONCLUSIONS: Women screened as experiencing higher IPV scores had higher Medicaid expenditures compared with women not currently experiencing IPV. Early IPV assessment partnered with effective clinic or community-based interventions may help to identify IPV earlier and reduce the health impact and cost of IPV.

Intimate partner violence incidence and continuation in a primary care screening program.

There are few longitudinal estimates of intimate partner violence (IPV) incidence and continuation. This report provides estimates of IPV incidence and continuation in women receiving health care in clinics participating in an IPV assessment and services intervention study. The Women's Experience with Battering Scale was used in combination with questions addressing physical and sexual assault to annually screen women for IPV. Between April 2002 and August 2005, 657 women in rural South Carolina consented and were screened at least twice. Among those with a current partner (n = 530), the majority (86.2%) had never experienced IPV. Among prevalent victims, IPV continued over time for 37%. IPV continuation rates were higher among older women and those who considered abuse as a problem in their relationship. Of those women who were IPV negative at time 1, IPV incidence at time 2 was 4.2%. A higher score on the Women's Experience with Battering Scale at time 1, a marker of psychological abuse, was a strong predictor of physical IPV incidence (p(trend) = 0.0001). These data suggest that the incidence of IPV over a short follow-up period is relatively low and that the majority of IPV desists over this short follow-up period.

Missed opportunities: intimate partner violence in family practice settings.

BACKGROUND: For women experiencing partner violence, women health care visits represent opportunities for physicians and patients to address intimate partner violence (IPV), a significant health threat for women. OBJECTIVES: The objectives were to estimate rates of physician documentation of IPV in medical records; characterize IPV+ women most likely to have IPV documented; and determine whether IPV screening increased IPV documentation. METHODS: Subjects were women ages 18-65 receiving primary care in two large family practice clinics. All were screened for IPV by study staff using a modified Index of Spouse Abuse and the Women's Experience with Battering scales. We selected and abstracted medical records for all women experiencing current IPV (N = 144) and a random sample of women never experiencing IPV (N = 147). RESULTS: Of 144 women screened as currently experiencing IPV, 14.7% were documented. Women most likely to have IPV documented were Caucasian, with higher WEB scores, and more likely to have an event that could trigger posttraumatic stress syndrome. Although the majority (41/56) of women currently in physically violent relationships did not plan to disclose IPV, those disclosing were significantly more likely to have IPV documented and documentation occurred after screening for 60% of women experiencing IPV. CONCLUSION: IPV screening increased documentation. IPV screening can provide the opportunity for patients to disclose IPV. Physicians then have the opportunity to compassionately connect patients with appropriate resources.