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The Gail model is used to predict the risk of breast cancer in women of diverse race/ethnic groups for clinical trial protocols. However, this model has only been validated in US white women. Using a nested case-control study design, we evaluated the diagnostic accuracy of the original Gail model (GM) and that of the revised Gail model algorithm for blacks/African-Americans (GM-B) in the Black Women's Health Study (BWHS). Risk profiles were derived via a self reported questionnaire at the time of enrollment into the BWHS in 1995. Biennial questionnaires were obtained from the participants to determine the incident cases of breast cancer. The study of 725 breast cancer cases and 725 controls revealed that the 5-year risk of breast cancer based on the GM ranged from 0.2% to 15.4% among cases and 0.2% to 13.6% among the controls. Based on the GM-B, the 5-year risk of breast cancer ranged from 0.2% to 8.7% among cases and 0.2% to 7.2% among the controls. The sensitivities of the GM and GM-B model with the standard cutoff of 1.7% were 17.9% (95% CI: 15.9-19.9%) and 4.1% (95% CI: 3.0-5.2), respectively. Both the original and the modified version of the Gail model underestimate the risk of developing breast cancer in African-American women. More importantly, the modified Gail Model (GM-B) does a worse job at predicting the development of breast cancer for blacks than the original model (GM). [ABSTRACT FROM AUTHOR]

Perceived discrimination may contribute to somatic disease. The association between perceived discrimination and breast cancer incidence was assessed in the Black Women's Health Study. In 1997, participants completed questions on perceived discrimination in two domains: 'everyday' discrimination (e.g., being treated as dishonest) and major experiences of unfair treatment due to race (job, housing, and police). Cox proportional hazards models were used to estimate incidence rate ratios, controlling for breast cancer risk factors. From 1997 to 2003, 593 incident cases of breast cancer were ascertained. In the total sample, there were weak positive associations between cancer incidence and everyday and major discrimination. These associations were stronger among the younger women. Among women aged less than 50 years, those who reported frequent everyday discrimination were at higher risk than were women who reported infrequent experiences. In addition, the incidence rate ratio was 1.32 (95% confidence interval: 1.03, 1.70) for those who reported discrimination on the job and 1.48 (95% confidence interval: 1.01, 2.16) for those who reported discrimination in all three situations-housing, job, and police-relative to those who reported none. These findings suggest that perceived experiences of racism are associated with increased incidence of breast cancer among US Black women, particularly younger women. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of this study was to evaluate the prognostic significance of the basal cell–like molecular breast cancer subtype with respect to locoregional recurrence and distant metastasis in African American women treated for breast cancer. Methods: A retrospective analysis was performed of the tumor registry database for all African American women diagnosed and treated for breast cancer from 1998 to 2005 who had assessable data for all 3 markers: estrogen, progesterone, and Her-2/neu. Results: A total of 372 patients were included in our study sample. Of these, 22 (6.1%) had locoregional recurrence, 35 (9.8%) had distant metastasis, and 301 (84.1%) had no evidence of breast tumor recurrence. The median follow-up time was 36 months. Compared with the other molecular subtypes the basal cell–like subtype showed a statistically significant association to distant metastasis: 15 (42.9%) vs 13 (37.1%), 4 (11.4%), and 3 (8.6%) (P < .001), respectively, for luminal A, Her-2/neu, and luminal B subtypes. The basal cell–like subtype was an independent predictor of distant metastasis (odds ratio, 5.8; 95% confidence interval, 1.5–22.0, P = .009). The molecular subtypes showed no statistically significant difference with respect to locoregional treatment administered and tumor stage at time of diagnosis. Conclusions: The basal cell–like molecular breast cancer subtype is an independent predictor of distant metastasis in African American women. [Copyright &y& Elsevier]

Relapsed/refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. Anti-CD19 chimeric antigen receptor (CAR) T cells, effective in systemic large B-cell lymphoma (LBCL), have shown responses in PCNSL and SCNSL in early reports, but with limited sample size. We, therefore, performed a comprehensive systematic review and meta-analysis of all published data describing CAR T-cell use in PCNSL and SCNSL. This identified 128 patients with PCNSL (30) and SCNSL (98). Our primary objectives were to evaluate CAR T-cell specific toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS] and cytokine release syndrome [CRS]) as well as response rates in these 2 populations. Seventy percent of patients with PCNSL had CRS of any grade (13% grade 3-4) and 53% had ICANS of any grade (18% grade 3-4). Comparatively, 72% of the SCNSL cohort experienced CRS of any grade (11% grade 3-4) and 48% had ICANS of any grade (26% grade 3-4). Of the patients with PCNSL, 56% achieved a complete remission (CR) with 37% remaining in remission at 6 months. Similarly, 47% of patients with SCNSL had a CR, with 37% in remission at 6 months. In a large meta-analysis of central nervous system (CNS) lymphomas, toxicity of anti-CD19-CAR T-cell therapy was similar to that of registrational studies in systemic LBCL with no increased signal of neurotoxicity observed. Encouraging efficacy was demonstrated in patients with CNS lymphoma with no discernible differences between PCNSL and SCNSL., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Objective: Sociodemographic and lifestyle factors, physical activity, diet, and nutrients are important in the understanding of obesity. The possibly direct or indirect nature of the associations among these factors and the eventual link to obesity is not well understood. In this study, we assess the indirect association between socio-demographic factors and obesity., Design: A case-control study involving African American women conducted at Howard University Cancer Center., Participants and Methods: One hundred ninety eight participants gave information on anthropometric measurements, intake of dietary supplements and nutrients, socio-demographic factors (age, marital status, income and education) and physical activity. Path analysis was utilized to assess associations between socio-demographic factors and obesity through physical activity, dietary supplements and nutrients, smoking or alcohol consumption., Main Results: The mean age of the participants was (55 ± 12 years), with 50% being obese (BMI ≥ 30 kg/m 2 ). Obesity level decreased by approximately 7% for every one level increase in education via its prior effect on vigorous physical activity. Age had a significant positive indirect effect on obesity through vigorous physical activity - with obesity levels increasing by approximately 6% for every one year increase in age via its prior effect on vigorous physical activity., Conclusions: Vigorous physical activity mediates the association between education and age on obesity., (Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: This study examined the effects of supervised and home-based exercise interventions on changes in metabolic syndrome (MetS) according to breast cancer risk (high vs low) in black women enrolled in the Focused Intervention on Exercise to Reduce Cancer (FIERCE) trial., Methods: Postmenopausal, obese, metabolically unhealthy black women, 45 to 65 years old, were randomized to supervised aerobic exercise (73 women), home-based walking-based exercise (69 women), or a control arm (71 women). Participants in the exercise arms underwent a 6-month intervention with study assessments conducted at the baseline and 6 months. The primary outcome measure was MetS (fasting glucose, waist circumference, blood pressure, serum triglycerides, and high-density lipoprotein [HDL]). The intervention effects on MetS, stratified by breast cancer risk as measured by the family history of breast cancer and model-based projected breast cancer risk, were examined with intent-to-treat analyses using generalized estimating equation models., Results: Among women with a family history of breast cancer, the exercise arms had lower mean MetS z scores, which suggested an improvement in the metabolic profile, than controls at 6 months (controls, + 0.55; home-based arm, -0.97, P < .01; supervised arm, -0.89, P < .01). Stratified analyses by projected breast cancer risk suggested similar but statistically nonsignificant findings, with those at high risk having more favorable changes in the MetS z score in the exercise arms versus the control arm. These changes were primarily attributable to changes in blood pressure, triglycerides, and HDL., Conclusions: Short-term aerobic activity regimens may improve the metabolic profile and thereby reduce breast cancer risk in obese, metabolically unhealthy black women at high risk for cancer. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Protein expression of Distal-less homeobox 4 (DLX4) was analyzed in inflammatory breast cancer (IBC) cases from an African-American (AA) population to determine if a) DLX4 gene over expression exists in this cohort and b) if the overexpression is associated with breast cancer clinicopathological characteristics (ER, PR, HER2, triple-negative). Twenty-nine blocks of formalin-fixed paraffin-embedded (FFPE) tissue from well-characterized human IBC cases were used for immunohistochemical staining (IHC). IHC results were assigned an intensity and percentage score. Percentage scores were assigned as 0, 1, 2, 3, or 4 and intensity scores were assigned 0, 1+, 2+ or 3+. For the analysis of the IHC, a percentage score of 3 or 4 and an intensity score of 2+ or 3+ were categorized as high. Chi-square or Fisher's exact tests were used to compare the high and low groups. In this cohort, 89.7% (26 out of 29) of IBC cases showed high percentages of positive cells staining for the DLX4 protein, while 40.0% (12 out of 30) of normal breast tissue from reduction mammoplasty cases demonstrated DLX4 expression ( p < 0.01). In IBC patients, 65.5% of cases showed a high level of staining intensity, compared to 20.0% of normal breast tissues (test, p = 0.001). Intensity to DLX4 was higher in the HER2 negative status (78.3%) than the HER2 positive status (16.7%) (test, p = 0.011). DLX4 expression is higher in the IBC cases in this study of an urban AA population than in normal breast tissue cases. HER2 negative status is positively associated with high intensity of DLX4., Competing Interests: CONFLICTS OF INTEREST All authors declare no competing interests.

The risk of cancer due to PCB exposure in humans is highly debated. In eastern Slovakia, high exposure of the population to organochlorines (especially PCBs) was associated with various disease and disorder pathways, viz., endocrine disruption, metabolic disorder & diabetes, and cancer, thereby disturbing several cellular processes, including protein synthesis, stress response, and apoptosis. We have evaluated a Slovak cohort (45-month children, at lower and higher levels of PCB exposure from the environment) for disease and disorder development to develop early disease cancer biomarkers that could shed new light on possible mechanisms for the genesis of cancers under such chemical exposures, and identify potential avenues for prevention.Microarray studies of global gene expression were conducted from the 45-month-old children on the Affymetrix platform followed by Ingenuity Pathway Analysis (IPA®) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR TaqMan low-density array (TLDA) was performed to further validate the selected genes on the whole blood cells of the most highly exposed children from the study cohort (n = 71). TP53, MYC, BCL2, and LRP12 differential gene expressions suggested strong relationships between potential future tumor promotion and PCB exposure in Slovak children. The IPA analysis further detected the most important signaling pathways, including molecular mechanism of cancers, prostate cancer signaling, ovarian cancer signaling, P53 signaling, oncostatin M signaling, and their respective functions (viz., prostate cancer, breast cancer, progression of tumor, growth of tumor, and non-Hodgkin's disease). The results suggest that PCB exposures, even at the early age of these children, may have lifelong consequences for the future development of chronic diseases.

Background: Oxidative stress and chronic inflammation can increase cellular levels of reactive oxygen species and lipid peroxidation (LPO) when associated with the pathogenesis of hepatocellular carcinoma (HCC), which can develop following the progression of steatosis, fibrosis and cirrhosis. Using a monoclonal antibody for cyclic γ-hydroxy-1, N 2 -propanodeoxyguanosine (γ-OHPdG), a promutagenic DNA adduct formed endogenously by LPO, we examined its formation across liver disease stages to understand it's potential role in HCC development., Methods: Formalin-fixed paraffin embedded (FFPE) liver tissue samples from 49 patients representing normal, steatosis, fibrosis, cirrhosis and HCC were stained for γ-OHPdG and 8-hydroxydeoxyguanosine (8-oxo-dG), an oxidative damage biomarker. Quantification of immunohistochemical (IHC) staining was performed using histological scoring of intensity and distribution. Using primary human hepatocytes (HH) and a stellate cell (SC) co-culture, immunocytochemical staining of γ-OHPdG and Nile Red was performed to determine if the formation of γ-OHPdG was consistent between the clinical sample disease stages and the in vitro steatotic and fibrotic conditions., Results: γ-OHPdG levels varied significantly between the stages of normal and steatosis, steatosis and fibrosis, and steatosis and cirrhosis (P≤0.005). There was a trend, although not significant, of increased levels of γ-OHPdG in HCC compared to the other groups. A strong correlation was observed (Pearson's, R 2 =0.85) between levels of γ-OHPdG and 8-oxo-dG across the disease spectrum. The increase of γ-OHPdG in steatosis and decrease in fibrosis was a pattern confirmed in an in vitro model using primary HH co-cultured with human SCs., Conclusions: γ-OHPdG was detected in FFPE liver tissues of patients with different stages of liver disease and in vitro studies, demonstrating that its formation is consistent with LPO in early stages of liver disease and suggesting that it may be a source of mutagenic DNA damage in liver disease progression., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics., Methods: We analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification. Utilizing immune histochemical analysis estrogen receptor (ER), progesterone receptor (PR), and (HER2/neu), were assessed. Cases were Luminal A (ER or PR+, Ki-67 < 14%), Luminal B (ER or PR+, Ki-67 = > 14% or ER or PR+ HER2+), HER2 (ER-, PR-, HER2+), and Triple Negative (ER-, PR-, HER2-) with basal-like phenotype. The relationship between MYC amplification and prognostic clinico-pathological characteristics was determined using chi square and logistic regression modeling., Results: Sixty-five (97%) of the tumors showed MYC gene amplification (MYC: CEP8 > 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p < 0.0001), stage (p < 0.001), metastasis (p < 0.001), and positive lymph node status (p = 0.039). MYC amplification was associated with HER2 status (p = 0.01) and tumor size (p = 0.01). High MYC amplification was seen in grade III carcinomas (MYC: CEP8 = 2.42), pre-menopausal women (MYC: CEP8 = 2.49), PR-negative status (MYC: CEP8 = 2.42), and ER-positive status (MYC: CEP8 = 2.4)., Conclusions: HER2 positive BCas in AA women are likely to exhibit MYC amplification. High amplification ratios suggest that MYC drives HER2 amplification, especially in HER2 positive, Luminal B, and subtypes of BCa.

Objective: We conducted a cluster-randomized trial evaluating an intervention that trained Chinese-American primary care physicians to increase their Chinese patients' colorectal cancer (CRC) screening., Methods: Twenty-five physicians (13 randomized to the intervention arm and 12 to the control arm) and 479 of their patients (aged 50-75 and nonadherent to CRC screening guidelines) were enrolled. The intervention, guided by Social Cognitive Theory, included a communication guide and 2 in-office training sessions to enhance physicians' efficacy in com- municating CRC screening with patients. Patients' CRC screening rates (trial outcome) and rating of physician communication before intervention and at 12-month follow-up were assessed. Intention-to-treat analysis for outcome evaluation was conducted., Results: Screening rates were slightly higher in the intervention vs. the control arm (24.4% vs. 17.7%, p = .24). In post hoc analyses, intervention arm patients who perceived better communication were more likely to be screened than those who did not (OR = 1.09, 95% CI: 1.03, 1.15). This relationship was not seen in the control arm., Conclusions: This physician-focused intervention had small, non-significant effects in increasing Chinese patients' CRC screening rates. Physician communication appeared to explain intervention efficacy. More intensive interventions are needed to enhance Chinese patients' CRC screening.

Self-rated health is a concept that has been linked to objective health outcomes but has not received much attention with regard to African-American men. The purpose of this study is to examine the relation of multiple factors (sociodemographic, health behaviors, personal health measures, and personality traits) with self-rated health in a sample of African-American men. The role personality plays in self-rated health in combination with other variables among African-American males has not thoroughly been explored. One hundred and seventy African-American men, ages 30-70 years old, were recruited for this study and completed a questionnaire assessing self-rated health, sociodemographics, health behaviors, personal health measures, and personality traits. Block-wise regression modeling was employed. The blocks were sociodemographics, health behaviors, personal health measures, and personality traits. Variables significantly associated with self-rated health in block-wise regression analyses at P < .05 (household income, BMI, number of health conditions, and neuroticism) were entered into the final multiple logistic regression model. Being obese was associated with greater odds of poor/fair self-rated health compared to being normal weight (OR = 9.02, 95 % CI 2.85-28.51, P < .001). Compared to reporting no health conditions, having more than one health condition was associated with greater odds of reporting poor/fair self-rated health (OR = 4.82, 95 % CI 1.18-19.69, P = .029). This study shows that existing medical conditions are important determinants of self-rated health among African-American men.

Background: Triple negative breast cancer (TNBC) tumors are estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor-negative. TNBC is responsive to chemotherapy, but chemotherapy might be underused in some patient subgroups. The goal of the present study was to characterize the patterns of chemotherapy use (uptake and completion) in TNBC patients., Patients and Methods: Women with primary invasive, nonmetastatic breast cancer were recruited in Washington, DC, and Detroit. Data were collected using a standardized telephone survey that captured sociocultural and health care process factors. Clinical data were abstracted from the medical records. We used χ 2 tests to access the association between the receipt of chemotherapy use (initiation and completion) and categorical variables, and t tests were used for continuous variables. Logistic regression models were used to evaluate the factors associated with chemotherapy uptake., Results: Women with TNBC (16% of sample) were more likely to be black than white (68% vs. 32%; P < .05). Among women with TNBC, 60% underwent chemotherapy. Chemotherapy uptake was greater for black than for white women (48.3% vs. 11.7%; P = .01) and in women without (vs. with) healthcare discrimination (35% vs. 25%; P = .04). In multivariable models, only race was associated with the receipt of chemotherapy. Black women were more likely to receive chemotherapy than were white women. The odds ratio of receiving chemotherapy by race was 4.1 (95% confidence interval, 1.3-13.1). Each 1-year increase in age was associated with a lower likelihood of chemotherapy completion (odds ratio, 0.9; 95% confidence interval, 0.826-0.981; P = .02). Women with at least some college were less likely to complete chemotherapy than were those with other education levels (P = .02)., Conclusion: A substantial number of TNBC patients failed to receive and/or complete chemotherapy. Differences in chemotherapy uptake by race and sociocultural factors diminished in multivariable models but age and stage remained significant. Suboptimal treatment among women with TNBC could contribute to adverse outcomes. Future investigations are necessary to assess whether the noninitiation and/or noncompletion of chemotherapy is clinically warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Many epidemiological studies base their classification of congenital cardiovascular malformations in newborns upon a single, initial diagnosis. This study aimed to evaluate the effect of subsequent diagnostic investigations on the results of epidemiological studies. We used diagnostic codes from the Baltimore-Washington Infant Study from the time of birth and at ~1 year of age. Odds ratios and 95% confidence intervals were used to identify associations between changes in diagnoses and infant characteristics, time period, that is, before and after introduction of color flow Doppler imaging, and diagnostic variables. Of the 3054 patients with data at both time points, 400 (13.1%) had diagnostic changes. For congenital cardiovascular malformations of early cardiogenesis, such as laterality and looping defects, conotruncal malformations, and atrioventricular septal defects, significant associations were observed between diagnostic change and case infants large for gestational age (odds ratio=0.22, p=0.01), diagnosed initially by echocardiography only (odds ratio=2.05, p=0.001), or with non-cardiac malformations (odds ratio=0.60, p=0.03). For all other congenital cardiovascular malformations, significant associations were observed with echocardiography-only diagnosis (odds ratio=1.43, p=0.04) and non-cardiac malformations (odds ratio=0.57, p<0.001). We found no statistically significant differences between risk factor odds ratios calculated using initial diagnoses versus those calculated using 1-year update diagnoses. Changes in congenital cardiovascular malformation diagnoses from birth to year 1 interval were significantly associated with infant characteristics and diagnostic modality but did not materially affect the outcome of risk factor associations.

Objective: The primary aims of this study were to: (1) characterize exercise stages of change among a sample of African-American men, (2) determine if exercise motivation was associated with self-reported exercise behavior, and (3) examine if groups of personal (i.e., age, BMI, income, educational attainment, and perceived health), psycho-social (i.e., exercise self-efficacy, personality type, social influence), and environmental factors (i.e., neighborhood safety) predicted stages of change for physical exercise among African-American men., Methods: One hundred seventy African-American male participants were recruited for this study (age: 47.63(10.23) years). Participants completed a self-report questionnaire assessing study variables. Multinomial logistic regression models were used to examine the association of exercise stages of change with an array of personal, psychosocial, and environmental factors., Results: BMI, exercise self-efficacy, and nighttime neighborhood safety were entered as independent variables in the full model. BMI and exercise self-efficacy continued to be significant predictors of exercise stages of change in the full model. Obese men had a 9.24 greater odds of being in the action stage of change than in the maintenance stage. Also, men reporting greater exercise self-efficacy had lower odds of being in the lower stages of change categories (pre-preparation, preparation, and action) than in the maintenance stage., Conclusion: Our results confirmed that using an ecological framework explained more of the variance in exercise stages of change than any of the individual components alone. Information gleaned from this study could inform interventionists of the best ways to create tailored exercise programs for African-American men.

The purpose of this study was to examine, through a randomized, controlled trial, the effects of a maternal carbohydrate-restricted diet on maternal and infant outcomes in gestational diabetes mellitus (GDM). Women diagnosed with GDM were randomly allocated into one of two groups: an intervention group that was placed on a lower-carbohydrate diet (35-40% of total calories) or a control group that was placed on the usual pregnancy diet (50-55% carbohydrate). A convenience sample of participants diagnosed with GDM (ages 18-45 years) was recruited from two different sites: one urban and low-income and the other suburban and more affluent. Individual face-to-face diet instruction occurred with certified diabetes educators at both sites. Participants tested their blood glucose four times daily. Specific socioeconomic status indicators included enrollment in the Supplemental Nutrition Program for Women, Infants and Children or Medicaid-funded health insurance, as well as cross-sectional census data. All analyses were based on an intention to treat. Although there were no differences found between the lower-carbohydrate and usual-care diets in terms of blood glucose or maternal-infant outcomes, there were significant differences noted between the two sites. There was a lower mean postprandial blood glucose (100.59 ± 7.3 mg/dL) at the suburban site compared to the urban site (116.3 ± 15 mg/dL) (P <0.01), even though there was no difference in carbohydrate intake. There were increased amounts of protein and fat consumed at the suburban site (P <0.01), as well as lower infant complications (P <0.01). Further research is needed to determine whether these disparities in outcomes were the result of macronutrient proportions or environmental conditions.

Purpose: Patient satisfaction provides an important illumination of the quality of care that is delivered. Satisfaction with care is often lower in Black women compared with their non-Hispanic White counterparts. Data are lacking regarding quality ratings of breast cancer patients. We examined racial disparities in ratings of the quality of cancer care in newly diagnosed Black (n = 217) and White (n = 152) patients., Methods: This was a cross-sectional observational study. Patients were recruited through hospitals and community outreach. Women with primary invasive, nonmetastatic breast cancer were eligible. Trained interviewers administered a standardized survey through telephone; clinical data were abstracted from medical records. The primary outcome, healthcare quality, was assessed using the PSQ-18, which assessed patients' ratings regarding four healthcare domains: interpersonal care, financial issues, technical ratings of physicians, and access and convenience. Independent variables included healthcare factors (e.g., suspicion toward the healthcare system), psychosocial factors (e.g., physicians' solicitation behaviors), and socioeconomic factors (e.g., limited access to resources). Multiple linear regression was used to evaluate associations between each healthcare quality domain and independent variables., Results: In univariate analysis, Black women reported lower ratings for four domains: technical (Black m = 3.99; White m = 4.26; p < .001), interpersonal (Black m = 4.15, White m = 4.35; p < .01), financial (Black m = 3.81, White m = 4.0, p < .001), and access and convenience (Black m = 3.92, White m = 4.08, p < .01). After adjusting for healthcare characteristics and psychosocial factors, trust in providers was significantly associated with three domains (β = 0.085, p < .001, technical; β = 0.066, p < .0001, interpersonal; β = 0.043, p < .0001, financial)., Conclusion: Racial disparities in ratings of healthcare quality were diminished across several domains after controlling for psychosocial and healthcare factors. Strategies aimed at improving self-efficacy in women with higher levels of mistrust may improve patient satisfaction.

Multivariate methods in meta-analysis are becoming popular and more accepted in biomedical research despite computational issues in some of the techniques. A number of approaches, both iterative and non-iterative, have been proposed including the multivariate DerSimonian and Laird method by Jackson et al. (2010), which is non-iterative. In this study, we propose an extension of the method by Hartung and Makambi (2002) and Makambi (2001) to multivariate situations. A comparison of the bias and mean square error from a simulation study indicates that, in some circumstances, the proposed approach perform better than the multivariate DerSimonian-Laird approach. An example is presented to demonstrate the application of the proposed approach.

The study examined the relation between social networks and physical activity behaviors among cancer survivors. The authors examined 873 cancer survivors (596 women, 277 men) 50 years of age or older who participated in the 2005 Health Information National Trends Survey. Multivariate logistic regression analysis showed that survivors who talked about health with friends/family were more likely to pay attention to new physical activity recommendations (OR = 2.89, CI [1.01, 8.33]). Female survivors were more likely to pay attention to new physical activity recommendations (OR = 2.65, CI [1.55, 4.53]) and more likely to have seen, heard, or read physical activity/exercise and cancer information within the past 12 months (OR = 2.09, CI [1.13, 3.85]) compared with their male counterparts. For male survivors, those who were a member of at least one community organization were more likely to pay attention to new physical activity/exercise recommendations (OR = 5.31, CI [1.32, 21.22]) than the men who were not members. Overall, cancer survivors with a social network (i.e., talking to family/friends about health) were more likely to pay attention to new exercise recommendations compared with those who did not have a social network. Significant differences were also observed by gender with physical activity levels, knowledge, and attitudes. Social networking is an important component in cancer survivorship and further research is needed to encourage social networking strategies that might facilitate in increasing physical activity behaviors among cancer survivors.

p16(INK4a) is a tumor suppressor gene, frequently hypermethylated in breast cancer; this epigenetic silencing of p16(INK4a) occurs early in carcinogenesis. The risk factors and functional consequences of p16(INK4a) methylation are unknown. Alcohol consumption, a breast cancer risk factor, impedes folate metabolism and may thereby alter gene methylation since folate plays a pivotal role in DNA methylation. In a cross-sectional study of 138 women with no history of breast cancer who underwent reduction mammoplasty, we studied breast cancer risk factors, plasma and breast folate concentrations, variation in one-carbon metabolism genes, p16(INK4a) promoter methylation and P16 protein expression. Logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). p16(INK4a) methylation was negatively correlated with P16 expression (r = -0.28; P = 0.002). Alcohol consumption was associated with lower breast folate (P = 0.03), higher p16(INK4a) promoter methylation (P = 0.007) and less P16 expression (P = 0.002). Higher breast folate concentrations were associated with lower p16(INK4a) promoter methylation (P = 0.06). Genetic variation in MTRR (rs1801394) and MTHFD1 (rs1950902) was associated with higher p16 (INK4a) promoter methylation (OR = 2.66, 95% CI: 1.11-6.42 and OR = 2.72, 95% CI: 1.12-6.66, respectively), whereas variation in TYMS (rs502396) was associated with less P16 protein expression (OR = 0.22, 95% CI: 0.05-0.99). Given that this is the first study to indicate that alcohol consumption, breast folate and variation in one-carbon metabolism genes are associated with p16(INK4a) promoter methylation and P16 protein expression in healthy tissues; these findings require replication., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01-1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility.

Background: Circulating adipokines may be associated with breast cancer risk. Genetic variants governing adipokines and adipokine receptors may also predict risk, but their effect on breast adipokine concentrations is unknown., Methods: We conducted a cross-sectional analysis of functional SNPs in 5 adipokine genes [adiponectin, leptin (LEP), and their receptors] among 85 cancer-free women who were undergoing reduction mammoplasty., Results: In multivariable-adjusted regression models, compared with the common GG genotype, the AA genotype of the LEP A19G SNP was associated with 27% lower plasma adiponectin [ratio, 0.73; 95% confidence interval (CI), 0.54-0.98] and leptin (ratio, 0.73; 95% CI, 0.55-0.96). Women with the AG genotype of LEP A19G had 39% lower breast leptin (ratio, 0.61; 95% CI, 0.39-0.97) compared with those with the GG genotype. No associations were observed for SNPs in the remaining genes., Conclusions: Genetic variation in LEP may alter endogenous adipokine concentrations in circulation and in breast tissues., Impact: These preliminary findings may support the hypothesis that genetic variation in adipokine genes modifies circulating adipokine concentrations and possibly leptin concentrations in local breast tissues, which may be associated with breast cancer risk., (©2014 American Association for Cancer Research.)

Heterozygotic loss of SYK, a non-receptor tyrosine kinase, gives rise to mouse mammary tumor formation where Syk protein levels are reduced by about half; loss of SYK mRNA is correlated with invasive cell behavior in in vitro models; and SYK loss has been correlated with distant metastases in patients. Here, allelic loss of the SYK gene was explored in breast ductal carcinoma in situ (DCIS) using fluorescence in situ hybridization and pyrosequencing, respectively, and in infiltrating ductal carcinoma (IDC) using genomic data from The Cancer Genome Atlas (TCGA). Allelic loss was present in a subset of DCIS cases where adjacent IDC was present. SYK copy number loss was found in about 26% of 1002 total breast cancer cases and 30% of IDC cases. Quantitative immunofluorescence revealed Syk protein to be six-fold higher in infiltrating immune cells compared with epithelial cells. This difference distorted tumor cell mRNA and protein levels in extracts. 20% of 1002 IDC cases contained elevated immune cell infiltration as estimated by elevated immune-specific mRNAs. In cases without immune cell infiltration, loss of SYK copy number was associated with a significant reduction of SYK mRNA. Here we define a 55 Gene Set consisting of Syk interacting, motility- and invasion-related genes. We found that overall survival was significantly reduced in IDC and Luminal A+B cases where copy number and mutations of these 55 genes were affected (Kaplan-Meier, Logrank test p-value 0.007141 and Logrank test p-value 0.001198, respectively). We conclude that reduction in Syk expression and contributions of genomic instability to copy number and mutations in the 55 Syk interacting genes significantly contribute to poorer overall patient survival. A closer examination of the role of Syk interacting motility and invasion genes and their prognostic and/or causative association with metastatic disease and patient outcome is warranted.

Background: The prevalence of obesity is disproportionately high in African American women, and consumption of fast foods and sugar-sweetened soft drinks is also especially high among African Americans., Objective: We investigated the relation of intakes of sugar-sweetened soft drinks and specific types of restaurant foods to obesity in the Black Women's Health Study., Design: In this prospective cohort study, 19,479 non-obese women aged 21-39 years at baseline were followed for 14 years (1995-2009). Dietary intake was assessed by validated food frequency questionnaire in 1995 and 2001., Main Outcome Measures: Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of intakes of restaurant foods and sugar-sweetened soft drinks with incident obesity., Results: Higher intakes of burgers from restaurants and sugar-sweetened soft drinks were associated with greater risk of becoming obese. The associations were present in models that included both factors and adjusted for overall dietary pattern. The HR of obesity in relation to restaurant burger consumption of > or = 2 times/week compared with < 5 times/year was 1.26 (95% CI: 1.14-1.40; P-trend<.001). For sugar-sweetened soft drink intake, the HR was 1.10 (95% CI: .99-1.23; P-trend = .14) for > or = 2 drinks/day compared with < 1 drink/month. The associations were stronger among women younger than age 30 with normal weight at baseline., Conclusions: Frequent consumption of burgers from restaurants and sugar-sweetened soft drinks contribute to obesity among young African American women.

Objective: To compare the efficacy of intermittent androgen deprivation therapy (IADT) vs continuous androgen deprivation therapy (CADT) for the treatment of advanced prostate cancer; we performed a meta-analysis of randomized controlled trials (RCTs), assessing the risks of disease progression, all-cause, and disease-specific mortality., Materials and Methods: We conducted a systematic search of several bibliographic systems to identify all RCTs of IADT in men with newly diagnosed metastatic or biochemical only prostate cancer. We abstracted outcome data, study characteristics, and participant demographics. We performed heterogeneity tests and calculated the summarized risk differences (RD) and risk ratios at 95% confidence intervals (CI), using inverse variance methods in random-effects approaches., Results: We identified 8 RCTs (N = 4664) comparing mortality between IADT and CADT. For all men combined, we observed small but nonsignificant differences in all-cause mortality (RD = 0.02, 95% CI = -0.02, 0.06), disease-specific mortality (RD = 0.04, 95% CI = -0.01, 0.08), and disease progression (RD = -0.03, 95% CI = -0.09, 0.04). Among the prespecified subgroup with histologically confirmed, newly diagnosed metastatic disease, we found no difference in overall survival (RD = 0.00, 95% CI = -0.09, 0.09)., Conclusion: We found no difference in overall survival, but a small increased risk in disease-specific survival for men treated with IADT relative to CADT was observed. IADT could be considered as an alternative to CADT because of better quality of life outcome. Patients should be informed of the possible risks and benefits of both therapies. More research confirming the benefits of IADT vs CADT is needed to inform treatment decisions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Weighting of studies in meta-analysis is usually implemented by using the estimated inverse variances of treatment effect estimates. However, there is a possibility of one study dominating other studies in the estimation process by taking on a weight that is above some upper limit. We implement an estimator of the heterogeneity variance that takes advantage of dominance adjusted weights. The performance of this estimator is compared with that of the commonly used estimator in meta-analysis, the DerSimonian-Laird estimator. Two test procedures for the overall treatment effect are proposed that are based on the quadratic form associated with the proposed heterogeneity variance estimator. An example is given to illustrate the application of these procedures. Copyright © 2013 John Wiley & Sons, Ltd., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: The Outpatient Physical Therapy Improvement in Movement Assessment Log (OPTIMAL) instrument was created to assess the perceived ability of patients receiving physical therapy in adult outpatient settings to perform actions or movements. Its properties must be studied to determine whether it accomplishes this goal., Objective: The objective of this study was to investigate the item properties of OPTIMAL with item response theory., Design: This investigation was a retrospective cross-sectional item calibration study., Methods: Data were obtained from the American Physical Therapy Association, which collected information from outpatient physical therapy clinics through electronic charting databases that included OPTIMAL responses. Item response theory analyses were performed on the trunk, lower-extremity, and upper-extremity subscales of the Difficulty Scale of OPTIMAL., Results: In total, 3,138 patients completed the Difficulty Scale of OPTIMAL at the baseline assessment. The subscale analyses met all item response theory assumptions. The items in each subscale showed fair discrimination. In all analyses, the subscales measured a narrow range of ability levels at the low end of the physical functioning spectrum., Limitations: OPTIMAL was originally intended to be administered as a whole. In the present study, each subscale was analyzed separately, indicating how the subscales perform individually but not as a whole. Another limitation is that only the Difficulty Scale of OPTIMAL was analyzed, without consideration of the Confidence Scale., Conclusions: OPTIMAL best measures low physical functioning at the baseline assessment in adult outpatient physical therapy settings. The addition of categories to each item and the addition of more challenging items are recommended to allow measurements for a broader range of patients.

We investigated insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 concentrations in histologically normal breast tissues and assessed their association with plasma concentrations, and breast cancer risk factors. IGF-1 and IGFBP-3 were assessed in plasma and breast tissues of 90 women with no history of any cancer and undergoing reduction mammoplasty. Pearson correlations and ANOVAs were used to describe plasma-breast associations and biomarker differences by breast cancer risk factors, respectively. Multivariable regression models were used to determine associations between risk factors, and breast IGF-1 and IGFBP-3. The mean age of the study sample was 37.3 years, 58 % were white, and generally these women were obese (mean BMI = 30.8 kg/m(2)). We observed no plasma-breast correlation for IGF-1, IGFBP-3, or IGF-1/IGFBP-3 (r = -0.08, r = 0.14, and r = 0.03, respectively; p-values >0.05). Through age- and BMI-adjusted analysis, BMI and years of oral contraceptive (OC) use were inversely associated with breast IGF-1 (p-values = 0.02 and 0.003, respectively) and age was associated with breast IGFBP-3 (p = 0.01), while breast IGF-1/IGFBP-3 was higher in blacks than whites (1.08 vs. 0.68, p = 0.04) and associated with age and BMI (p-values = 0.03 and 0.002, respectively). In multivariable-adjusted models, some breast cancer risk factors studied herein explained 24, 10, and 15 % of the variation in breast IGF-1, IGFBP-3, and IGF-1/IGFBP-3, respectively. While reasons for the lack of plasma-breast hormone correlations in these cancer-free women are unknown, several factors were shown to be associated with breast concentrations. The lack of correlation between blood and tissue IGF-1 and IGFBP-3 suggests that studies of breast cancer risk assessing blood IGF-1 and IGFBP-3 may have important limitations in understanding their role in breast carcinogenesis.

Purpose: Dairy and meat consumption may impact breast cancer risk through modification of hormones (e.g., estrogen), through specific nutrients (e.g., vitamin D), or through products formed in processing/cooking (e.g., heterocyclic amines). Results relating meat and dairy intake to breast cancer risk have been conflicting. Thus, we examined the risk of breast cancer in relation to intake of dairy and meat in a large prospective cohort study., Methods: In the Black Women's Health Study, 1,268 incident breast cancer cases were identified among 52,062 women during 12 years of follow-up. Multivariable (MV) relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using Cox proportional hazards models., Results: Null associations were observed for total milk (MV RR = 1.05, 95 % CI 0.74-1.46 comparing ≥1,000-0 g/week) and total meat (MV RR = 1.04, 95 % CI 0.85-1.28 comparing ≥1,000 < 400 g/week) intake and risk of breast cancer. Associations with intakes of specific types of dairy, specific types of meat, and dietary calcium and vitamin D were also null. The associations were not modified by reproductive (e.g., parity) or lifestyle factors (e.g., smoking). Associations with estrogen receptor (ER) positive (+), ER negative (-), progesterone receptor (PR) +, PR-, ER+/PR+, and ER-/PR- breast cancer were generally null., Conclusions: This analysis of African-American women provides little support for associations of dairy and meat intake with breast cancer risk.

Background: Blood adipokines are associated with breast cancer risk; however, blood-breast adipokine correlations and factors that explain variation in adipokines are unknown., Methods: Plasma (n = 155) and breast (n = 85) leptin and adiponectin were assessed by immunoassays in women with no history of cancer. Multivariable-adjusted regression models were used to determine breast adipokine associations., Results: Through body mass index (BMI)-adjusted analyses, we initially observed positive plasma-breast correlations for leptin (r = 0.41, P = 0.0002) and adiponectin (r = 0.23, P = 0.05). The positive plasma-breast correlation for leptin was strongest among normal weight women (r = 0.62), whereas the correlation for adiponectin was strongest among obese women (r = 0.31). In multivariable models, adjusting for BMI, demographic, reproductive, and lifestyle factors, plasma leptin was not associated with breast leptin, and only the highest quartile of plasma adiponectin was associated with tissue levels. Of the risk factors investigated, those that contributed most to the variation in breast tissue adipokines were BMI and race for leptin, oral contraceptive use and smoking status for adiponectin., Conclusions: Although we report positive plasma-breast adipokine correlations overall, plasma adipokine concentrations may not be good surrogates for breast concentrations among all women. Predictors of breast adipokines vary, depending on subject characteristics, possibly explaining inconsistent epidemiologic results and they implicate differing pathways toward carcinogenesis., Impact: A clearer understanding of the relationships between plasma adipokines and their levels within the target organ is necessary to better understand the impact of these hormones on breast cancer risk. Future studies are needed to identify additional factors associated with breast adipokines in target tissues., (2012 AACR)

Background: Lipid levels, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, have been reported to be associated with breast cancer risk., Methods: We studied African American women (97 breast cancer cases and 102 controls) accrued through a population-based, case-control study in the Washington, DC metropolitan area during 1997 and 1998. Plasma lipid levels were measured using enzymatic methods. Logistic regressions (adjusted for age, age at menarche, parity, previous alcohol consumption, and education) were used to explore the associations between lipid levels and breast cancer., Results: Through multivariable-adjusted regression, we observed a significant inverse association between breast cancer risk and increasing levels of total cholesterol (OR=.46, 95% Cl = .25-.85) and LDL (OR = .41, 95% CI = .21-.81), whereas lower levels of HDL were associated with a significant increase in risk (OR = 1.99, 95% CI = 1.06-3.74)., Conclusions: Our data demonstrate significant reductions in breast cancer risk with high levels of total cholesterol and significant increase in risk when HDL levels are low. These data are in support of a protective effect of cholesterol which has been reported in other populations; further, these findings add to the literature in an understudied population, African American women.

Objectives/hypothesis: To determine whether the endoscopic or sublabial transseptal transsphenoidal approach for pituitary surgery has superior outcomes or decreased complication rates., Study Design: Retrospective meta-analysis of literature., Methods: A MEDLINE search was conducted identifying all relevant literature in the English language from 1998 through 2010. Studies explicitly identifying pure sublabial or completely endoscopic approaches were included. Meta-analysis comparing the two techniques was performed for multiple outcome measures utilizing a random effects approach., Results: A total of 21 endoscopic studies (n = 2,335) and 17 sublabial studies (n = 2,565) met inclusion criteria. Analysis revealed significantly superior rates of gross tumor resection (79% vs. 65%, P < .0001), as well as lower rates of cerebral spinal fluid leak (5% vs. 7%, P < .01), septal perforation (0% vs. 5%), and postoperative epistaxis (1% vs. 4%, P < .0001) for the endoscopic approach compared to the sublabial approach. There was no difference between the two techniques in the incidence of meningitis, diabetes insipidus, or resolution of hormonal abnormality. Hospital stay (P = .01) was shorter for endoscopic surgery compared to sublabial surgery, and there was no significant difference in terms of length of operation., Conclusions: The sublabial transsphenoidal approach has been the gold standard for pituitary surgery for many years. However, meta-analysis of the recent literature demonstrates superior outcomes and decreased postoperative complications with the endoscopic approach, potentially justifying a shift toward endoscopic pituitary surgery., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

A better understanding of the risk of local recurrence (LR) will facilitate therapeutic decision making in the management of early breast cancers. In the present study, we investigated whether telomere length in the normal breast epithelial cells surrounding the tumor is predictive of breast cancer LR; 152 women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this nested case-control study. Cases (patients had LR) and controls (patients had no LR) were matched on year of surgery, age at diagnosis and type of surgery. Telomere fluorescent in situ hybridization was used to determine the telomere length using formalin fixed paraffin-embedded breast tissues. Small telomere length variation (TLV), defined as the coefficient variation of telomere lengths among examined cells, in normal epithelial cells adjacent to the tumor was significantly associated with a 5-fold (95% confidence interval = 1.2-22.2) increased risk of breast cancer LR. When the subjects were categorized into quartiles, a significant inverse dose-response relationship was observed with lowest versus highest quartile odds ratio of 15.3 (P(trend) = 0.012). Patients who had large TLV had significantly better 10 year recurrence free survival rate compared with patients who had small TLV (80 versus 33%). The present study revealed that TLV in normal epithelial cells adjacent to tumor is a strong predictor of breast cancer LR. If confirmed by future studies, TLV in normal epithelial cells adjacent to tumor has the potential to become a promising biomarker for predicting breast cancer LR after breast conserving surgery.

MicroRNAs (miRs) are small, non-protein coding transcripts involved in many cellular functions. Many miRs have emerged as important cancer biomarkers. In the present study, we investigated whether miR levels in breast tumors are predictive of breast cancer local recurrence (LR). Sixty-eight women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this study. Breast cancer patients with LR and those without LR were matched on year of surgery, age at diagnosis, and type of surgery. Candidate miRs were identified by screening the expression levels of 754 human miRs using miR arrays in 16 breast tumor samples from 8 cases with LR and 8 cases without LR. Eight candidate miRs that showed significant differences between tumors with and without LR were further verified in 52 tumor samples using real-time PCR. Higher expression of miR-9 was significantly associated with breast cancer LR in all cases as well as the subset of estrogen receptor (ER) positive cases (p = 0.02). The AUCs (Area Under Curve) of receiver operating characteristic (ROC) curves of miR-9 for all tumors and ER positive tumors are 0.68 (p = 0.02) and 0.69 (p = 0.02), respectively. In ER positive cases, Kaplan-Meier analysis showed that patients with lower miR-9 levels had significantly better 10-year LR-free survival (67.9% vs 30.8%, p = 0.02). Expression levels of miR-9 and another miR candidate, miR-375, were also strongly associated with ER status (p<0.001 for both). The potential of miR-9 as a biomarker for LR warrants further investigation with larger sample size.

Context: Cigarette tobacco smoke is a potent environmental contaminant known to adversely affect health including fertility and pregnancy., Objective: To examine the associations between second-hand cigarette tobacco-smoke exposure, or active smoking and serum concentrations of steroid hormones using tandem mass spectrometry., Design: Healthy women (18-45 y) from the general community in the Metropolitan Washington, DC were recruited at the follicular stage of their menstrual cycle. Participants were assigned to one of three study groups: active smokers (N=107), passive smokers (N=86), or non-smokers (N=100). Classifications were based on a combination of self-reporting and serum cotinine concentrations., Methods: Serum androgens, estrogens, progestins, androstenedione, aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 11-deoxycortisol and 25-hydroxy-vitamin D3 (25-OHVitD3) and cotinine were measured by isotope dilution tandem mass spectrometry (LC/MS/MS) (API-5000). Kruskal-Wallis tests were used to assess median differences among the three groups, with Dunn's multiple comparison test for post hoc analysis., Results: Serum estrone, estradiol, and estriol concentrations were lower in active and passive smokers than in non-smokers. The three study groups differed significantly in serum concentrations of 16-OHE1, aldosterone and 25-OHVitD3, as well as in the ratios of many of the steroids. Pair-wise comparison of the groups demonstrated significant differences in hormone concentrations between (i) smokers and non-smokers for aldosterone: (ii) passive smokers and non-smokers for aldosterone, progesterone and estriol. Moreover, for smokers and passive smokers, there were no significant differences in these hormone concentrations., Conclusions: Smoke exposure was associated with lower than normal median steroid hormone concentrations. These processes may be instrumental in explaining some adverse effects of tobacco smoke on female health and fertility., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Colorectal adenomas are benign lesions that may be precursors to colorectal cancer. No studies of African American women have investigated dietary patterns and the risk of developing colorectal adenomas. We examined data from the Black Women's Health Study to determine whether dietary patterns are associated with the risk of developing colorectal adenomas., Methods: This is a prospective cohort study of 59,000 participants followed biennially since 1995. During 155,414 person-years of follow-up from 1997 to 2007 among women who had had at least one screening colonoscopy, 620 incident cases of colorectal adenomas were identified. By using Cox regression models, we obtained incidence rate ratios (IRR) for colorectal adenoma in relation to quintiles of each of two dietary patterns, adjusting for other colorectal adenoma risk factors., Results: Two dietary patterns, Western and prudent, were utilized to assess the association between dietary intake and adenoma risk. The highest quintile of prudent diet, relative to the lowest quintile, was significantly associated with 34% lower colorectal adenoma risk overall (IRR = 0.66; 95% CI, 0.50-0.88; P(trend) < 0.01). Higher scores on the Western pattern were associated with a higher risk of developing colorectal adenoma (IRR = 1.42; 95% CI, 1.09-1.85 for the highest quintile relative to the lowest; P(trend) = 0.01)., Conclusion: Our findings suggest that African American women may be able to reduce their risk of developing colorectal adenomas by following a prudent dietary pattern and avoiding a more Western pattern., Impact: A dietary modification could have a strong impact in colorectal adenoma prevention in African American women., (©2011 AACR.)

Background: Complementary and alternative medicine (CAM) use, including herbals and multivitamin supplements, is quite common in the U.S., and has been shown to be highest in breast cancer survivors. However, limited data are currently available for CAM usage among African Americans. Thus, we sought to determine the prevalence of multivitamins, folic acid and herbal supplement usage in African American breast cancer survivors, and to compare the characteristics of users and nonusers., Methods: A cohort study of breast cancer survivors, who completed the 1999 Black Women's Health Study questionnaire and self-reported having been diagnosed with breast cancer between 1995 and 1999, comprised the study population. In this study, the intake of natural herbs, multivitamins and folic acid at least three days per week within the past two years was used as a proxy for typical usage of this complimentary alternative medicine (CAM) modality., Results: A total of 998 breast cancer survivors were identified. Overall, 68.2% had used either herbals or multivitamin supplements or both. The three most frequently used herbals were garlic (21.2%), gingko (12.0%), and echinacea (9.4%). The multivariate analysis determined that single marital status (OR=1.58; 95%CI: 1.04-2.41), and alcohol consumption of 1-3 drinks per week (OR=1.86, 95%CI: 1.28-2.68) were significantly associated with increased herbal use. Multivitamin use was significantly lower among obese women (OR=0.66, 95%CI: 0.46-0.94) and current smokers (OR=0.53, 95%CI: 0.34-0.82)., Conclusions: A significant number of African American breast cancer survivors are using herbals and multivitamins as CAM modality. Additional research is needed to understand the impact of herbals and multivitamins in African American breast cancer survivors.

The BH3-like motif-containing inducer of cell death (BLID) is an intronless gene localized on 11q24.1. Loss of that region has frequently been reported in early-onset breast cancer and is significantly associated with poor prognosis and reduced survival. Downregulation of BLID is associated with younger age, triple-negative phenotype, and reduced disease-free and overall survival of breast cancer patients. In this study, we investigated allelic loss of BLID in breast tumor specimens from 78 women with invasive breast cancer using 2 dinucleotide polymorphic markers closely linked to the BLID gene (no intragenic marker for BLID is available). Seventy-three cases were informative. Overall, loss of heterozygosity (LOH) at the BLID locus was detected in 32% of the informative cases (23/73). However, in patients 40 years old and younger, LOH was detected in 50% of the cases (9/18). Patients aged 40 years and younger were significantly more likely to experience LOH than those aged 41-55 years (p = 0.04). Specifically, the odds of BLID loss for patients aged 40 years and younger were 3.7 times the odds of loss for patients aged 41-55 years (95% CI, 1.1-13). Our findings suggest a tumor suppressor role of the BLID gene in early-onset breast cancer., (Copyright © 2011 S. Karger AG, Basel.)

Perceived discrimination has been shown to be related to health screening behavior. The present study examines the effect of discrimination on cancer screening among women in the Black Women's Health Study. Five self-report items measured discrimination in everyday life and three items measured experiences of major discrimination. Logistic regression was used to test associations of discrimination with Pap smear, mammography, or colonoscopy utilization. At the start of follow-up, 88.8% had a Pap smear in the previous year, 52.7% had a mammogram, and 20.0% had received a colonoscopy. Both everyday and major discrimination were associated with not having received a Pap smear, even after adjusting for other variables. Discrimination was not associated with mammography or colonoscopy utilization. In conclusion, perceived everyday and major discrimination is associated with poorer utilization of Pap smears for cervical cancer screening among Black women.

The Gail model has been used to predict invasive breast cancer risk in women using risk factors of age, age at menarche, age at first live birth, number of first-degree relatives with breast cancer, and number of previous benign breast biopsies. However, this model underestimates breast cancer risk in African-American women. The Contraceptive and Reproductive Experience (CARE) model has been developed to replace the Gail model in predicting breast cancer risk in African-American women. In a sample of 883 women who participated in the breast cancer screening program at Howard University Cancer Center, we compared the breast cancer risk estimates from the Gail model and the CARE model. The mean 5-year breast cancer risk was 0.88% (Range: 0.18-6.60%) for the Gail model and 1.29% (Range: 0.20-4.50%) for the CARE model. Using the usual cutoff-point of 1.67% or above for elevated risk, there is a significant difference in the proportion of women with elevated breast cancer risk between the Gail and the CARE models (McNemar's test, p < 0.0001). For both models, there was a significant mean risk difference between those with and without a family history of breast cancer (Wilcoxon rank-sum test, p < 0.0001). Our results confirm the need for validation of the Gail model in African-Americans and diversity in research. Although these findings are not perfect and perhaps not definitive, they are additive in the discussions during counseling and risk assessment in African-Americans. Furthermore, these findings will be complemented by new technologies such as genomics in refining our ability to assess risk.

This study investigates the dimensional structure of the Center for Epidemiologic Studies Depression (CES-D) scale in US Black women with and without history of cancer via single-group and multi-group analyses. The CES-D questionnaire was administered in 1999 to 50,774 black women who are participants in the Black Women's Health Study (BWHS). For our analysis, we utilized a group of 690 women with a history of at least one of the three types of cancer (breast cancer, colon cancer or lung cancer) and an age-matched group of 1,380 healthy women with no history of any cancer or other chronic conditions including myocardial infarctions, stroke, angina, diabetes, lupus, and sarcoidosis. Three a priori hypothesized models were tested via confirmatory factor analysis: single-, three- and four-factor structures. The four-factor model provided the best fit and remained largely invariant across the groups when tested via multi-group comparisons. Two internal consistency measures of the scale (Cronbach's alpha coefficient and split-half coefficient) were also shown to be satisfactory. We concluded that the CES-D scale is appropriate for use in black women regardless of their cancer status.

Objective: To analyze whether the local-regional surgical treatments (breast-conserving therapy, mastectomy) resulted in different overall survival, distant metastasis-free survival, and locoregional recurrence-free survival rates for the various molecular breast cancer subtypes., Summary Background Data: Molecular gene expression profiling has been proposed as a new classification and prognostication system for breast cancer. Current recommendation for local-regional treatment of breast cancer is based on traditional clinicopathologic variables., Methods: Retrospective analysis of 372 breast cancer cases with assessable immunohistochemical data for ER, PR, and Her-2/neu receptor status, diagnosed from 1998 to 2005. Molecular subtypes analyzed were luminal A, luminal B, basal like, and Her-2/neu., Results: No substantial difference was noted in overall survival, and locoregional recurrence rate between the local-regional treatment modalities as a function of the molecular breast cancer subtypes. The basal cell-like subtype was an independent predictor of a poorer overall survival (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.28-4.97, P < 0.01) and a shorter distant metastasis-free survival time (HR = 3.61, 95% CI 1.27-10.2, P < 0.01), and showed a tendency toward statistical significance as an independent predictor of locoregional recurrence (HR = 3.57, 95% CI 0.93-13.6, P = 0.06)., Conclusions: The basal cell-like subtype is associated with a worse prognosis, a higher incidence of distant metastasis, and may be more prone to local recurrence when managed with breast-conserving therapy.

Background: Breast cancer is currently regarded as a heterogeneous disease classified into various molecular subtypes using gene expression analysis. These molecular subtypes include: basal cell-like, Her-2/neu, luminal A, and luminal B., Objectives: To analyze the prevalence and clinicopathologic associations for molecular breast cancer subtypes in premenopausal and postmenopausal African-American women., Design: A retrospective analysis of all African-American women diagnosed with breast cancer from 1998 to 2005, who had assessable data for ER, PR, and Her-2/neu status. Molecular subtype classification was done based on immunohistochemical surrogates for ER, PR, and Her-2/neu status obtained from Howard University tumor registry for each patient. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and Her-2/neu (ER-, PR-, and HER2+)., Outcome Measures: We analyzed the prevalence of molecular breast cancer subtypes in a population of African-American women and determined their associations with patient demographics and clinicopathologic variables: node status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival., Results: The luminal A subtype was the most prevalent in our study sample (55.4%) compared with (11.8%) luminal B, (21.2%) basal cell-like, and (11.6%) Her-2/neu subtypes. The molecular subtypes did not differ by menopausal status. However, when stratified into age-specific groups, the basal cell-like subtype (57.1%) was the most prevalent in the age group <35 y compared with luminal A, luminal B, and Her-2/neu subtypes at 25.0%, 14.3%, and 3.6%, respectively. The basal cell-like subtype also showed an age-specific bimodal distribution with a peak in the <35 y and 51 to 65 y age groups. The basal cell-like and the Her-2/neu subtypes showed an increased association with clinicopathologic variables portending a more aggressive clinical course when compared with luminal A subtype. A paradoxical inverse relationship between the expression of p53 and Bcl-2 protooncoprotein was noted in the molecular subtypes. Breast cancer-specific survival differed significantly among the molecular subtypes (P < 0.04), with the basal cell-like and Her-2/neu subtypes having the poorest outcome., Conclusions: The high prevalence of the basal cell-like subtype in the young premenopausal African-American women aged <35 y could be a contributory factor to the poorer prognosis of breast cancer observed in this cohort of patients.

Introduction: Breast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women., Methods: A retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998-2005, was performed., Results: The luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01). The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31)., Conclusion: The high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.

Background: Physical activity is associated with a reduced risk of colon cancer, but the effect of activity on colorectal adenomas, which are precursors to colon cancer, is uncertain. The influence of physical activity on colorectal adenomas among African-American women is of particular interest because African-American women have an increased risk of colon cancer relative to other U.S. women., Methods: We prospectively assessed the relation of physical activity to the incidence of colorectal polyps among African-American women. We followed 45,400 women in the Black Women's Health Study from 1997 to 2003. Data were obtained by biennial mailed questionnaires. During 287,029 person-years of follow-up, 1,390 women reported having been diagnosed with colorectal polyps. A review of medical records of 58 women who reported colorectal polyps indicated that 59% had adenomas and 41% had hyperplastic polyps. We converted hours per week of vigorous exercise and hours per week of walking to metabolic equivalent (MET)-hours. We estimated incidence rate ratios with Cox proportional hazard models, controlling for age, body mass index, smoking, family history of colorectal cancer, and education., Results: For total MET-hours/wk spent in walking and vigorous exercise, the incidence rate ratio decreased from 0.94 for <5 MET-hours/wk to 0.72 for >or=40 MET-hours/wk (P(trend) = 0.01). The inverse association was apparent among most subgroups examined, including women who may be at higher risk of colorectal adenomas because of being obese., Conclusions: Increased physical activity is associated with a reduced incidence of colorectal polyps among African-American women.

The effect of two noniterative heterogeneity variance estimators on two test procedures for the overall treatment effect using the log odds ratio as the outcome measure is investigated. Using simulated significance levels, it is shown that in addition to being sensitive to changes in the magnitude of the heterogeneity variance, the standard test procedure in meta-analysis (or multicenter clinical trials) is also sensitive to the heterogeneity variance estimator used and attains significance levels that are far from the prescribed level. A second test procedure by Hartung [Hartung, J. (1999). An alternative method for meta-analysis. Biometrical J. 41:901-916], is shown to exhibit good control of type I error probability regardless of changes in the magnitude of the heterogeneity variance and the heterogeneity variance estimator used.