Postmenopausal African American Women Research Articles

Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe Study

Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe Study

Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women’s Health Initiative SHARe Study

Genome-wide association studies (GWAS) of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G × E) interactions in post-menopausal African-American and Hispanic women from the Women's Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumference ratio (WHR) adjusted for multidimensional-scaling-derived axes of ancestry and age was run in race-stratified data with 871,512 SNPs available from African-Americans (N = 8,203) and 786,776 SNPs from Hispanics (N = 3,484). Tests of G × E interaction at all SNPs for recreational physical activity (m h/week), dietary energy intake (kcal/day), alcohol intake (categorical), cigarette smoking years, and cigarette smoking (ever vs. never) were run in African-Americans and Hispanics adjusted for ancestry and age at interview, followed by meta-analysis of G × E interaction terms. The strongest evidence for concordant G × E interactions in African-Americans and Hispanics was for smoking and marker rs10133840 (Q statistic P = 0.70, beta = -0.01, P = 3.81 × 10(-7)) with BMI as the outcome. The strongest evidence for G × E interaction within a cohort was in African-Americans with WHR as outcome for dietary energy intake and rs9557704 (SNP × kcal = -0.04, P = 2.17 × 10(-7)). No results exceeded the Bonferroni-corrected statistical significance threshold.

Abstract LB-327: Validation of a breast cancer risk prediction model in African American women

Abstract Existing breast cancer risk prediction models, such as the Breast Cancer Risk Assessment Tool (BCRAT), are less reliable for predicting risk in African American women than they are in white women. Gail et al. (2007) modified the BCRAT model for risk prediction of breast cancer in African American women based on data from the Women's Contraceptive and Reproductive Experiences (CARE) study; the CARE model uses information on a woman's age, age at menarche, family history of breast cancer, and number of previous breast biopsies to estimate absolute breast cancer risk. They validated the model among postmenopausal African American women aged 50 or older in the Women's Health Initiative and found it to be well calibrated but with limited discriminatory accuracy. We assessed calibration and discrimination of the CARE model in both pre- and postmenopausal women using data from the Black Women's Health Study (BWHS), an ongoing follow-up study of African American women 21-69 years of age at enrollment in 1995. We based our validation on 36,713 women who at baseline were 35 years and older, had no history of cancer, and had complete data on the risk factors in the model. We compared the expected number of invasive breast cancer cases predicted by the model to the observed number of cases identified in the BWHS overall and within subgroups of risk factors. We measured the discriminatory accuracy using the concordance statistic, the area under the receiver-operating curve. During a mean follow-up of 9.4 years, we identified 773 invasive breast cancer cases. The model predicted 691.9 cases, yielding an expected-to-observed ratio (E/O) of 0.90 (95% CI: 0.83, 0.96). Of the risk factors included in the CARE model, the E/O ratio was lowest among women with a previous biopsy (E/O = 0.76; 95% CI: 0.66, 0.88); the E/O ratio was close to 0.90 across categories of the other factors in the model. The CARE model does not include age at first birth, which was included in the BCRAT; we found the CARE model to be well calibrated among women with an age at first birth <25 years (E/O = 0.99; 95% CI: 0.90, 1.09) but not among women with an age at first birth ≥25 years (E/O = 0.73; 95% CI: 0.64, 0.83). In addition, risk was underestimated among women with a body mass index (BMI) at age 18 <20 kg/m*2 (E/O = 0.79; 95% CI: 0.71, 0.87). Results did not differ between premenopausal and postmenopausal women. The age-specific concordance statistic was 0.59 (95% CI: 0.54, 0.64), 0.58 (95% CI: 0.54, 0.61), 0.56 (95% CI: 0.52, 0.60), and 0.55 (95% CI: 0.49, 0.61) for women aged 35-39, 40-49, 50-59, and 60-69 years, respectively, which is comparable to the discriminatory accuracy reported in previous validations of the CARE and BCRAT models. The risk underestimation in particular subgroups of women suggests that the CARE model may be improved by the inclusion of age at first birth (as in the BCRAT) and perhaps other risk factors such as BMI at age 18. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-327. doi:1538-7445.AM2012-LB-327

Relationship between diabetes risk and admixture in postmenopausal African-American and Hispanic-American women.

Type 2 diabetes is more prevalent in African-Americans (AFAs) and Hispanic-Americans (HAs) than in European-Americans. We assessed whether continental admixture was correlated with diabetes risk in these high-risk groups. We estimated the proportion of sub-Saharan African (AFR), Amerindian (AMI) and European admixture using 92 ancestry-informative marker genotypes in 16,476 AFA and HA women from the Women's Health Initiative. Cox regression models were used to examine the association between admixture and diabetes risk, with and without accounting for socioeconomic status (SES) and adiposity measurements. AFR admixture was significantly associated with diabetes risk in AFA women when adjusting for entry age, neighbourhood SES and BMI or waist/hip ratio (WHR) (all p < 0.0001). In HA women, AMI admixture had significant associations with diabetes risk that remained significant after adjustment for SES and BMI (all p < 0.0005). In both AFAs and HAs, SES showed significant negative associations while BMI or WHR had significant positive associations with diabetes risk, with and without adjustment for genetic admixture. In AFAs, admixture, SES and BMI/WHR each independently contribute to diabetes risk after accounting for each of the other factors; in HAs, admixture, SES and BMI each independently contribute to diabetes risk after accounting for each of the other factors, whereas admixture is not significantly associated with diabetes risk after accounting for SES and WHR. The findings emphasise the importance of considering both genetic and environmental causes in the aetiology of type 2 diabetes.

The role of anthropometric and nutritional factors on breast cancer risk in African-American women

While the role of nutrition, physical activity and body size on breast cancer risk has been extensively investigated, most of these studies were conducted in Caucasian populations. However, there are well-known differences in tumour biology and the prevalence of these factors between African-American and Caucasian women. The objective of the present paper was to conduct a review of the role of dietary factors, anthropometry and physical activity on breast cancer risk in African-American women. Twenty-six research articles that presented risk estimates on these factors in African-American women and five articles involving non-US black women were included in the current review. Racial disparities in the impact of anthropometric and nutritional factors on breast cancer risk. African-American and non-US black women. Based on the few studies that presented findings in African-American women, an inverse association with physical activity was found for pre- and postmenopausal African-American women, while the association for anthropometric and other dietary factors, such as alcohol, was unclear. Studies assessing the effect by molecular subtypes in African-American women were too few and based on sample sizes too small to provide definitive conclusions. The effect of certain nutrition and lifestyle factors on breast cancer in African-American women is not starkly distinct from those observed in white women. However, there is an enormous need for further research on this minority group to obtain more confirmatory findings.

Abstract PL03-03: High-risk/triple-negative breast cancer and African ancestry

Abstract Variation in breast cancer incidence and outcome is well-documented between geographically separated populations on a worldwide basis. Several factors contribute to these trends and observations, including lifestyle, diet, environment, culture, and genetics. The United States is characterized by a richly-diverse population with regard to ethnic/racial background as well as all of the other factors listed that account for differences in cancer burden. Disparities in breast cancer burden between ethnic/racially-delineated subsets of the American population are well-documented by the Surveillance, Epidemiology, and End Results (SEER) Program, the Centers for Disease Control (CDC) and the North American Association of Central Cancer Registries (NAACCR)(1–3). Ward et al (1) demonstrated the expected adverse effects of poverty on cancer survival for men and women of all ethnic backgrounds, and prevalence of socioeconomic disadvantages is higher for ethnic minorities such as African Americans and Hispanic/Latino Americans. Even within discrete strata of socioeconomic status however, disparities in cancer survival are seen between communities defined by ethnic background. However as shown by Newman et al (4), breast cancer survival studies that account for socioeconomic status reveal a persistent nearly-30% higher mortality hazard for African American compared to White American patients. Disentangling the effects of race/ethnicity, culture, and socioeconomic resources on cancer risk is further confounded by the fact that we rely on self-reporting of patient race/ethnic background when in fact an individual's lineage may have included contributions from several different ancestral populations. The ethnic/racial composition of the U.S. is shifting in favor of increased diversity. An improved understanding of the multi-factorial etiology of healthcare disparities is therefore critical for improved cancer control among contemporary as well as future generations of our diverse patient population. Clinical trials and the study of breast cancer subtypes are shedding more light on breast cancer risk as it correlates with ethnic/racial background. Among the 156,570 prospectively-followed postmenopausal participants of the Women's Health Initiative protocols followed for a median of 6.3 years, risk of being diagnosed with estrogen receptor-negative, high-grade breast cancer was nearly five time higher for African American compared to White American women (adjusted OR = 4.70, 95% CI = 3.12 to 7.09), and mortality was higher for the African American breast cancer patients as well (HR = 1.79, 95% CI = 1.05 to 3.05). Carey et al (5) analyzed immunohistochemical surrogate markers for basal breast cancer subtypes among the Carolina Breast Cancer Study dataset, and reported an increased prevalence of these more aggressive tumors among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non-African American women (16%) of any age (P&amp;lt;.001). Albain et al (6) reviewed the collective, organ-specific protocols of the Southwest Oncology Group (SWOG) and found that equal treatments within the context of the standardized clinical trials mechanism, except for the hormonally-driven cancers such as breast and prostate. For these cancer sites, significantly worse outcomes were observed for the African American clinical trial participants. The triple-negative molecular marker status has become a common clinical surrogate to identify the basal breast cancer subtype, and several population-based as well as single institution studies have now documented an approximately two-fold higher risk of triple-negative breast cancer among African American compared to White American women. Furthermore, an expanding database of international breast cancer studies are now revealing even higher risk of triple-negative breast cancers among western sub-Saharan African women. It is possible that use of genotyping technology will refine studies of cancer risk related to ancestral heritage. Use of Ancestry Informative Markers (AIMs), also called Ethnic Difference Markers, may provide a more objective strategy for defining and quantifying racial/ethnic background. These AIMs can estimate the extent of an individual's West African, European, Native American, East Asian, and South Asian ancestry (7–17). Ongoing studies seek to evaluate the optimal genetic patterns and markers for these types of association studies. This presentation will include preliminary findings from an ongoing international collaboration between the University of Michigan and the Komfo Anoyke Teaching Hospital in Kumasi, Ghana. This research partnership involves the study of breast disease patterns and molecular markers in western, sub-Saharan Africans compared with those of African Americans and White Americans. This collaborative effort has demonstrated a correlation between frequency of high-risk/triple-negative breast cancer and presumed extent of African ancestry (18), and it has also served as a model for establishing other international oncology research programs. (19, 20)

Relationship between hypertension and admixture in post-menopausal African American and Hispanic American women

To assess the relationship between ethnicity and hypertension using individual admixture and blood pressure measurements, we performed a cross-sectional study of African American and Hispanic American (HA) women enrolled in the Women's Health Initiative. The admixture odds ratio for systolic and diastolic hypertensive risk was determined using linear regression models in which the proportional measurements of European (EUR), sub-Saharan African (AFR) and Amerindian (AMI) admixture was analyzed using ancestry informative markers. In both African-American women (n=10,147) and HA women (n=4908) there was a significant positive association between hypertension and African admixture (P<10(-4)). This relationship was observed for both systolic and diastolic hypertension examined as a continuous or dichotomous trait, and whether age, body mass index, years since menopause and a measurement of socioeconomic status were used as covariates. The odds ratio associated with AFR admixture in a dichotomous model of hypertension was 3.06 (95% confidence interval 2.72-3.45). AMI admixture was associated with lower odds of hypertension and appeared to be more protective, relative to EUR admixture. These data show that African admixture increases the risk for hypertension and provide additional support for evaluating therapeutic efficacy and conducting genetic analyses of hypertension in different ethnic groups.

Comparison Of Changes In Fasting Glucose Levels After Aerobic Exercise Training In Pre- And Post-menopausal African American Women

African American women have the greatest incidence rate of type II diabetes amongst all ethnic groups in the United States. Moreover, menopause confers a greater risk for the onset of type II diabetes. Aerobic exercise training (AEXT) has been well demonstrated to improve glucose metabolism and aid in the prevention of type II diabetes; however the effects of menopausal status on the exercise-induced adaptations in glucose metabolism have not been previously investigated. PURPOSE: To investigate the effects of a 6-month AEXT intervention on fasting plasma glucose levels in pre- and post-menopausal African American women without clinically diagnosed type II diabetes. METHODS: 17 female African Americans who were sedentary, non-diabetic (<126 mg/dL), non-smoking, free of cardiovascular disease and not on antihypertensive medication completed 6 months of supervised AEXT (3 days/week, 65% of VO2max, 40 min/session). 6-weeks prior to initiation of AEXT, subjects underwent dietary stabilization and were required to follow an AHA low fat, low salt diet for the duration of the study. Before and after AEXT, fasted blood samples were collected and measured for plasma glucose levels. RESULTS: Pre- (n = 9; 51.7 ± 5.1 yrs) and post-menopausal (n = 8; 54.3 ± 6.2 yrs) women were similar in BMI, % body fat, and VO2max at baseline. The absolute change (pre-menopause: -8.4 ± 7.6; post-menopause: 0.87 ± 6.1 mg/dL; p =.015) and % change (pre-menopause: -8.8 ± 7.6; post-menopause: 1.4 ± 7.5%; p =.014) in plasma glucose levels from pre-AEXT levels were significantly different between pre- and post-menopausal women. This difference remained significant after adjusting for the change in BMI and % body fat. Sub-analysis of each menopause group showed that plasma glucose levels were significantly decreased in pre-menopausal women after AEXT (pre: 93.1 ± 9.3; post: 84.6 ± 8.6 mg/dL; p =.010), however there was no significant change in plasma glucose levels in post-menopausal women (pre: 89.3 ± 9.7; post: 90.2 ± 7.9 mg/dL; p =.701). CONCLUSIONS: In African American women, fasting plasma glucose levels improved following AEXT in pre-menopausal, but remained unchanged in post-menopausal women. These preliminary findings suggest that exercise-induced adaptations in glucose metabolism are attenuated in post-menopausal African American women.

Abstract 948: Investigation of breast cancer susceptibility loci in the PAGE study

Abstract Introduction: Recent genome-wide association studies (GWAS) of breast cancer have identified single nucleotide polymorphisms (SNPs) in more than 20 loci associated with increased risk of breast cancer, primarily in European-descent populations. Yet, the biological mechanisms underlying most of these genetic variants as well as their effect sizes in other populations differing by race/ethnicity remains unknown. We investigated breast cancer associations with previously reported SNPs in white and African American (AA) women from the Population Architecture using Genomics and Epidemiology (PAGE) study. Methods: We selected 28 common SNPs reported in breast cancer GWAS or candidate-gene association studies representing 21 different breast cancer susceptibility loci for our analysis. These SNPs were genotyped in 5878 white and 904 AA postmenopausal women sampled from the Women's Health Initiative Study, which is part of the PAGE consortium. Invasive breast cancer cases (n = 1366 in whites and n=226 in AA) were identified prospectively and confirmed via medical records review. We coded SNPs using additive genetic models and used logistic regression to estimate per allele odds ratios (OR) and 95% confidence intervals (CI). Race/ethnicity-specific models were adjusted for age; adjustment for risk factors such as body mass index, current smoking and postmenopausal hormone therapy (HT) were also investigated. Results: In whites, we observed statistically significant (p&amp;lt;0.05) associations for 14 of 28 SNPs; strongest associations were seen for SNPs in 10q26.13/FGFR2 and 16q12.1/TOX3, with p&amp;lt;0.0001. In AA, 5 of the 28 SNPs located in 1p11.2/NOTCH, 5q11.2/MAP3K1, 10q26.13/FGFR2, and 11p15.5/LSP1 were associated with breast cancer at p&amp;lt;0.05, while an additional 4 were marginally significant at p&amp;lt;0.07. FGFR2 has been strongly implicated as a breast cancer susceptibility locus, though a causal variant has not yet been identified (Udler et al., 2009). Our ORs of ∼1.2 in whites are consistent with prior reports. Additionally, we observed elevated odds of breast cancer, OR (95%CI) = 1.3(1.0-1.7), in AA for a SNP in this locus, rs2981578 (G allele). Conclusions: We confirm prior breast cancer associations in postmenopausal white women and report associations in 4 loci that extend to AA women. Our next steps will be to evaluate associations by cancer subtype and expand investigations in AA to include additional genotype data and women from the other PAGE studies. These results in women differing by race/ethnicity contribute to future research on breast cancer etiology by providing data that can be used to inform the identification and fine mapping of causal breast cancer variants. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 948. doi:10.1158/1538-7445.AM2011-948

Obesity is associated with breast cancer in African-American women but not Hispanic women in South Los Angeles

Obesity is considered a risk factor for breast cancer. Modifying life styles that reduce obesity offers the potential for prevention and improved outcomes from cancer. The effects of obesity and breast cancer among African-American women and Hispanic women have been explored in a limited number of studies. The objective of the current study was to investigate the association of obesity with breast cancer in a minority cohort. This was a cross-sectional study of 471 African-American and Hispanic women with and without breast cancer in South Los Angeles. Data regarding body mass index (BMI) and clinical factors were obtained by medical record abstraction. Data were assessed using logistic regression with multivariate analysis. Kaplan-Meier survival analysis was used to assess disease-free survival. Women with breast cancer were more likely to be obese (BMI >30 kg/m(2)) than women without breast cancer (odds ratio [OR], 2.0; P = .01). There was a significant association of being overweight or obese and breast cancer among postmenopausal women (OR, 2.3 [P = .03] and 2.9 [P < .01], respectively). The association between obesity and breast cancer was significant only among African-American women (OR, 2.70; P < .01) and was especially significant among postmenopausal African-American women (OR, 4.8; P < .01). There was a borderline significant association between obesity and later disease stage at diagnosis (P = .06). An association also was observed between higher BMI (for cutoff points of both 30 kg/m(2) and 28 kg/m(2)) and poorer disease-free survival (P = .045 and P = .019, respectively). The current data suggested an association between obesity and breast cancer, especially among postmenopausal women and most significantly in the African-American cohort.

Metabolic effects of soy supplementation in postmenopausal Caucasian and African American women: a randomized, placebo-controlled trial

Metabolic effects of soy supplementation in postmenopausal Caucasian and African American women: a randomized, placebo-controlled trial

Abstract A96: Breast tumor subtypes and survival outcomes in African American and Latina patients in South Los Angeles

Abstract Background: Recent studies have shown that minority women, in particular African American are more likely to express Triple Negative (TN) tumors compared to Non-Hispanic Whites. TN tumors are more difficult to treat this may be one of the factors contributing to disparities in disease outcome and overall survival. In our study, we have studied a cohort of African American and Latina women with equal socio-economic status (SES) and access to care. The purpose of this study was to determine if these two ethnic groups with equal SES and access to care had differences in disease outcome and if this difference was related to tumor subtypes. We have also examined cellular and molecular markers associated with tumor subtypes and disease outcome. Methods: A total of 300 subjects were retrospectively selected. 156 were African American and 144 Latina. Demographic, pathologic, and clinical follow-up information were collected from existing database. The prevalence of breast cancer subtypes within racial and menopausal subsets was examined and the associations with tumor size, lymph nodal status, staging, and histologic grade were determined by logistic regression. Disease-free survival (DFS) was analyzed by Kaplan-Meier survival curves with log-rank test. Gene and protein signatures associated with PI3kinase/Akt and the CD44/CD24 expression profiles were analyzed by immunohistochemistry analysis (IHC) in different tumor subtypes. Results: The TN or basal-like breast cancer subtype (ER/PR/HER2 negative) was more prevalent among premenopausal African American women (36%) compared to postmenopausal African Americans (28.1); premenopausal Latina women (31 %); and postmenopausal Latinas (17%) (p=0.05). The HER2+/ER-subtype was more prevalent among premenopausal Latina women (17%) than postmenopausal Latinas (14%), postmenopausal African American women (9%), and premenopausal African American women (3%) (p=0.046). Prevalence of Luminal A and Luminal B breast cancer subtypes were similar with race and menopausal status. Compared to Luminal A, basal-like tumors were more poorly differentiated (OR=6.4, p&amp;lt;0.001) and more likely to have CD44+/CD24-phenotype, while HER2+/ER-tumors were more associated with large tumor size (OR=3.1, p=0.01) and CD24+ phenotype. The Luminal B tumors were also more likely to be associated with larger tumor size and were poorly differentiated (OR=3.0, p=0.002). Patients with basal-like and HER2+/ER-tumors had significant shorter DFS compared to patients with Luminal A tumors (log rank=11.97, p=0.0005 and log rank=8.95, p=0.002). The DFS was also reduced significantly in patients with Luminal B tumors than Luminal A tumors (log rank=7.09, p=0.007). The poor disease outcome in those patients may due to have increased plasma IGF-I, activated tissue pAkt and loss of functional FOXO1 A. Conclusions: Our study suggests a highest prevalence of basal-like tumors (triple negative) in premenopausal African American women, followed by premenopausal Latina women. Premenopausal Latina women also had a higher prevalence of HER2+/ER-tumors. DFS was poor in both ethnic groups with either basal like tumors or those with HER2+/ER-tumors. Activation of pAkt in the tumor tissue was a significant contributor to the poor disease outcome. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A96.

Effect of soy supplementation on regional lean and fat mass and resting metabolic rate in caucasian and African American postmenopausal women

Effect of soy supplementation on regional lean and fat mass and resting metabolic rate in caucasian and African American postmenopausal women

Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women

We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy. To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women. In this cross-sectional study, 89 HIV+ and 95 HIV- postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry. The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV- women (74-78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r=0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)(2)D and CD4 count or between serum 25OHD, 1,25(OH)(2)D or PTH and type of ART. In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.

A Case-Control Study of Body Mass Index and Breast Cancer Risk in White and African-American Women

Large body size has been associated with decreased risk of breast cancer in premenopausal women but with increased risk in postmenopausal women. Limited information is available about African-American women and differences by estrogen and progesterone receptor status. We analyzed data from the Women's Contraceptive and Reproductive Experiences Study among 3,997 white and African-American breast cancer case patients diagnosed in 1994 to 1998 and 4,041 control participants ages 35 to 64 years. We calculated multivariate odds ratios (OR) as measures of relative risk of breast cancer associated with self-reported body mass index (BMI) at age 18 and 5 years before diagnosis (recent BMI). Risk tended to decrease with increasing BMI at age 18 years in all women [OR(BMI > or = 25 kg/m(2) versus < 20 kg/m(2)) = 0.76; 95% confidence interval (CI), 0.63-0.90; P(trend) = 0.005] and with recent BMI in premenopausal women (OR(BMI > or = 35 kg/m(2) versus < 25 kg/m(2)) = 0.81; 95% CI, 0.61-1.06; P(trend) = 0.05), unmodified by race. Among postmenopausal white but not African-American women, there was an inverse relation between recent BMI and risk. High recent BMI was associated with increased risk of estrogen receptor- and progesterone receptor-positive tumors among postmenopausal African-American women (OR(BMI > or = 35 kg/m(2) versus < 25 kg/m(2)) = 1.83; 95% CI, 1.08-3.09; P(trend) = 0.03). Among women at age 35 to 64 years, BMI at age 18 years is inversely associated with risk of breast cancer, but association with recent BMI varies by menopause status, race, and hormone receptor status. Our findings indicate that studies of BMI and breast cancer should consider breast cancer subtypes.

Postmenopausal African American Women Demonstrate Greater Age-Associated Declines in Lean Tissue Mass Compared to Caucasians

Aging is associated with a decline in lean tissue mass (LM). African American (AA) postmenopausal women have higher LM than Caucasians (C). We hypothesized that due to their higher LM, AA women would demonstrate an accelerated decline in LM compared to age-matched C subjects, and the decline in LM would be related to deconditioning (Lower Peak VO2). PURPOSE: To compare the rate of decline in lean body mass with age between postmenopausal AA and C women, and determine if peak VO2 is related to the decline in LM. METHODS: 226 C and 89 AA women of comparable age (58 ± 7 vs. 60 ± 7 yrs, respectively) had total LM and appendicular tissue mass (AM) measured by Dual Energy X-ray Absorptiometry (DXA). Peak VO2 (ml/kg/min) was measured during a progressive graded exercise treadmill test to exhaustion. Group differences were analyzed by Student's t-tests, and relationships were analyzed using Linear Regression. Data are mean ± standard deviation. RESULTS: AA had significantly higher LM (44.3 ± 5.1 vs. 41.3 ± 5.1 kg, p = 0.002) and AM (20.3 ± 2.6 vs. 18.1 ± 2.5 kg, p < 0.001) than C, respectively. Conversely, AA had 12% lower peak VO2 compared to C (p < 0.001). AA also demonstrated a greater rate of decline in LM with age compared to C (-0.34 vs. -0.18 kg of LM/year, p = 0.06), respectively. Aging was associated with a decline in peak VO2 (r = -0.31, p < 0.001), but there was no difference in this decline between AA and C (p = NS). Peak VO2 was significantly associated with LM when adjusting for age (r = 0.42, p = 0.006). However, when controlling for race, peak VO2 was associated with LM in C (r = 0.31, p = 0.014) but not in AA (p = NS). CONCLUSIONS: Postmenopausal AA women demonstrate a higher LM across age compared to C, but tend to have a greater rate of decline in LM with age. Postmenopausal AA women have a significantly lower peak VO2 compared to C. The decline in peak VO2 with age in AA is not associated with the decline in LM. Future research should focus on investigating the mechanisms for the larger rate of decline of LM in postmenopausal AA women with age and develop strategies to attenuate that decline.

Strategies for Recruitment of Healthy Premenopausal Women into the African American Nutrition for Life (A NULIFE) Study.

Although African American women have an overall lower incidence of breast cancer, African American women <40 years of age are more likely than Caucasian women of all ages and postmenopausal African American women to be diagnosed with breast cancer and exhibit tumor characteristics associated with poorer survival. To begin to address this disparity, studies must be conducted to examine breast cancer preventive factors in this subpopulation of women. However, the strategies needed to recruit younger African American women have not been well defined. In this study, we assessed methods used for recruiting and retaining healthy premenopausal African American women into the African American Nutrition for Life (A NULIFE) Study. The number of women contacted, enrolled, and retained by each recruitment strategy and the efficiency of individual strategies were calculated. Overall, recruitment through social networking was most effective in contacting large numbers of healthy premenopausal African American women. The worksite recruitment method was the most efficient recruitment strategy employed, with a ratio of 40%. The study participants (n = 164) were more likely to be >or=35 years of age and have completed some college. Additionally, the interpersonal relationships recruitment approach proved most efficient (33%) in retaining participants who completed the yearlong study. The findings from this study add to the evolving research literature on minority recruitment strategies for research studies but specifically address effective recruitment of healthy young premenopausal African American women. The results demonstrate the need to use multiple recruitment strategies when recruiting this subgroup of African American women.

Clinical Significance of p53 and bcl-2 Protein Coexpression Phenotypes in Molecular Breast Cancer Subtypes of Pre-menopausal and Post-menopausal African-American Women

With the current classification of breast carcinoma into molecular subtypes with distinct prognosis and response to therapy, we sort to assess the clinical significance of p53 and bcl-2 coexpression phenotypes in invasive breast tumors and correlate this to the different molecular breast cancer subtypes in African-American women. We performed a retrospective analysis of data on p53 and bcl-2 expression. Results were correlated to molecular breast cancer subtypes, and clinicopathologic variables of prognostic significance. Our study sample included all African-American women diagnosed with breast cancer from 1998 to 2005. Twenty-seven (27.6%) per cent of cases in our study sample over-expressed p53, whereas 69.3 per cent over-expressed bcl-2 protein. A significant inverse correlation was observed between expression of p53 and bcl-2. Combined analysis of p53 and bcl-2 showed that 53.2 per cent of the tumors displayed p53(-)bcl-2(+) phenotype which was significantly associated with the luminal A subtype, whereas 11.6 per cent displayed the p53(+)bcl-2(-) phenotype which was significantly associated with the basal cell-like and Her-2/neu. Neither p53 expression nor bcl-2 expression individually or in combination were of independent prognostic significance. p53(+)bcl-2(-) phenotype is significantly correlated with the basal cell-like subtype and may be associated with the biologic aggressiveness of this cohort of molecular breast cancer.

Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women

FGFR2 and MAP3K1 are members of the RAS/RAF/MEK/ERK-signaling pathway and have been identified from genome-wide association studies to be breast cancer susceptibility genes. Potential interactions of these genes and their role with respect to tumor markers, hormonal factors and race on breast cancer risk have not been explored. We examined FGFR2 and MAP3K1 variants, breast tumor characteristics and hormone exposures in a population-based case-control sample of 1225 European-American (EA) and 584 African-American (AA) women. FGFR2 rs1219648 and rs2981582 genotypes were significantly associated with breast cancer in EA only in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and HER2/Neu-negative (HER2-) tumors. MAP3K1 was not associated with breast cancer in EA women, but it was associated with breast cancer in AA women, again limited to ER+, PR+ and HER2- tumors. An interaction was observed between combined hormone replacement therapy use and FGFR2 rs1219648 genotypes on breast cancer risk in EA women (P = 0.010). Finally, we observed a significant interaction between MAP3K1 rs889312 and FGFR2 rs2981582 (P = 0.022) in AA but not EA women. These results confirm that FGFR2 and MAP3K1 are involved in breast cancer susceptibility and confer their effects primarily in ER+ and PR+ tumors. We further report that these genes confer their effects in HER2- tumors, interact with one another to confer breast cancer susceptibility in AA women and interact with hormone exposures in AA and EA women.

The Relationship Between Achievement of Walking Goals and Exercise Self-Efficacy in Postmenopausal African American Women

The purpose of this study was to investigate the relationship between the achievement of walking goals and exercise self-efficacy in African American women. A convenience sample of 43 postmenopausal African American women was used. Participants engaged in a 6-week walking program with 2 walking goals. Exercise self-efficacy was assessed using the Self-Efficacy for Exercise Questionnaire and semistructured interviews. Participants who met the brisk walking goals demonstrated higher exercise self-efficacy than those who did not (P = .003). Those who met the average daily step goal tended to have higher exercise self-efficacy (P = .108) compared with those who did not. Women who have high levels of exercise self-efficacy before engaging in an exercise program have more successful outcomes. Enhancing exercise self-efficacy in African American women should be a goal of every healthcare professional.