Supplement Use and Chemotherapy-Induced Peripheral Neuropathy in a Cooperative Group Trial (S0221): The DELCaP Study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) can interfere with daily function and quality of life, and there are no known preventive approaches. In a cohort of breast cancer patients receiving paclitaxel as part of a clinical trial (SWOG 0221), we examined the use of dietary supplements both before diagnosis and during treatment in relation to CIPN. Methods: At registration to S0221, 1225 breast cancer patients completed questionnaires regarding the use of multivitamins and supplements before and at diagnosis. A second questionnaire at six months queried use during treatment. Supplement use was evaluated in relation to CIPN, assessed via the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v. 3.0) and the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity (FACT/GOG-Ntx) subscale. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed with logistic regression for the CTCAE analyses and ordinal regression for the FACT/GOG-Ntx analyses. Results: Multivitamin use before diagnosis was associated with reduced symptoms of CIPN (CTCAE-adjusted OR = 0.60, 95% CI = 0.42 to 0.87; FACT/GOG-Ntx-adjusted OR = 0.78, 95% CI = 0.61 to 1.00). Use during treatment was marginally inversely associated with CIPN (CTCAE-adjusted OR = 0.73, 95% CI = 0.49 to 1.08; FACT/GOG-Ntx-adjusted OR = 0.77, 95% CI = 0.60 to 0.99). Other supplement use, either before diagnosis or during treatment, was not statistically significantly associated with CIPN. Conclusions: Multivitamin use may be associated with reduced risk of CIPN, although individual dietary supplement use did not appreciably affect risk. Multivitamin use could be a surrogate for other related behaviors that are the actual drivers of the association with reduced CIPN. Without prospective randomized trials of vitamin supplementation, recommendations for use or changes to clinical practice are clearly not warranted.

Breast cancer risk factor associations differ for pure versus invasive carcinoma with an in situ component in case-control and case-case analyses.

PURPOSE: Invasive ductal carcinoma (IDC) is diagnosed with or without a ductal carcinoma in situ (DCIS) component. Previous analyses have found significant differences in tumor characteristics between pure IDC lacking DCIS and mixed IDC with DCIS. We will test our hypothesis that pure IDC represents a form of breast cancer with etiology and risk factors distinct from mixed IDC/DCIS. METHODS: We compared reproductive risk factors for breast cancer risk, as well as family and smoking history between 831 women with mixed IDC/DCIS (n = 650) or pure IDC (n = 181), and 1,620 controls, in the context of the Women's Circle of Health Study (WCHS), a case-control study of breast cancer in African-American and European-American women. Data on reproductive and lifestyle factors were collected during interviews, and tumor characteristics were abstracted from pathology reports. Case-control and case-case analyses were conducted using unconditional logistic regression. RESULTS: Most risk factors were similarly associated with pure IDC and mixed IDC/DCIS. However, among postmenopausal women, risk of pure IDC was lower in women with body mass index (BMI) 25 to <30 [odds ratio (OR) 0.66; 95 % confidence interval (CI) 0.35-1.23] and BMI ≥ 30 (OR 0.33; 95 % CI 0.18-0.67) compared to women with BMI < 25, with no associations with mixed IDC/DCIS. In case-case analyses, women who breastfed up to 12 months (OR 0.55; 95 % CI 0.32-0.94) or longer (OR 0.47; 95 % CI 0.26-0.87) showed decreased odds of pure IDC than mixed IDC/DCIS compared to those who did not breastfeed. CONCLUSIONS: Associations with some breast cancer risk factors differed between mixed IDC/DCIS and pure IDC, potentially suggesting differential developmental pathways. These findings, if confirmed in a larger study, will provide a better understanding of the developmental patterns of breast cancer and the influence of modifiable risk factors, which in turn could lead to better preventive measures for pure IDC, which have worse disease prognosis compared to mixed IDC/DCIS.

Genetic variants in one-carbon metabolism genes and breast cancer risk in European American and African American women.

Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We conducted a comprehensive analysis of SNPs in eleven genes involved in one-carbon metabolism and risk of breast cancer in 1,275 European-American (EA) and 1,299 African-American (AA) women who participated in the Women's Circle of Health Study. Allele frequencies varied significantly between EA and AA populations. A number of these SNPs, specifically in genes including MTR, MTRR, SHMT1, TYMS and SLC19A1, were associated with overall breast cancer risk, as well as risk by estrogen receptor (ER) status, in either EA or AA women. Associations appeared to be modified by dietary folate intake. Although single-SNP associations were not statistically significant after correcting for multiple comparisons, polygenetic score analyses revealed significant associations with breast cancer risk. Per unit increase of the risk score was associated with a modest 19 to 50% increase in risk of breast cancer overall, ER positive or ER negative cancer (all p < 0.0005) in EAs or AAs. In summary, our data suggest that one-carbon metabolizing gene polymorphisms could play a role in breast cancer and that may differ between EA and AA women.

Intake of energy-dense foods, fast foods, sugary drinks, and breast cancer risk in African American and European American women.

Limiting energy-dense foods, fast foods, and sugary drinks that promote weight gain is a cancer prevention recommendation, but no studies have evaluated intake in relation to breast cancer risk in African American (AA) women. In a case-control study with 1692 AA women (803 cases and 889 controls) and 1456 European American (EA) women (755 cases and 701 controls), odds ratios (OR) and 95% confidence intervals (CI) for risk were computed, stratifying for menopausal and estrogen receptor (ER) status. Among postmenopausal EA women, breast cancer risk was associated with frequent consumption of energy-dense foods (OR = 2.95; 95% CI: 1.66-5.22), fast foods (OR = 2.35; 95% CI: 1.38-4.00), and sugary drinks (OR = 2.05; 95% CI: 1.13-3.70). Elevated risk of ER+ tumors in EA women was associated with energy-dense (OR = 1.75; 95% CI: 1.14-2.69) and fast foods (OR = 1.84; 95% CI: 1.22-2.77). Among AA women, frequent fast food consumption was related to premenopausal breast cancer risk (OR = 1.97; 95% CI: 1.13-3.43), and with ER+ tumors. Energy adjustment attenuated risk estimates in AA women, while strengthening them among EA women. Frequent consumption of energy-dense and fast foods that have poor nutritive value appeared to increase breast cancer risk in AA and EA women, with differences by menopausal status and ER status.

Variants of estrogen-related genes and breast cancer risk in European and African American women.

It has been observed previously that compared with women of European ancestry (EA), those of African ancestry (AA) are more likely to develop estrogen receptor (ER)-negative breast cancer, although the mechanisms have not been elucidated. We tested the associations between breast cancer risk and a targeted set of 20 genes known to be involved in estrogen synthesis, metabolism, and response and potential gene-environment interactions using data and samples from 1307 EA (658 cases) and 1365 AA (621 cases) participants from the Women's Circle of Health Study (WCHS). Multivariable logistic regression found evidence of associations with single-nucleotide polymorphisms (SNPs) in the ESR1 gene in EA women (rs1801132, odds ratio (OR)=1.47, 95% CI=1.20-1.80, P=0.0002; rs2046210, OR=1.24, 95% CI=1.04-1.47, P=0.02; and rs3020314, OR=1.43, 95% CI=1.19-1.70, P=0.00009), but not in AA women. The only other gene associated with breast cancer risk was CYP1A2 in AA women (rs2470893, OR=1.42, 95% CI=1.00-2.02, P=0.05), but not in EA women. When stratified by ER status, ESR1 rs1801132, rs2046210, and rs3020314 showed stronger associations in ER-positive than in ER-negative breast cancer in only EA women. Associations with the ESR1 SNPs in EA women also appeared to be stronger with longer endogenous estrogen exposure or hormonal replacement therapy use. Our results indicate that there may be differential genetic influences on breast cancer risk in EA compared with AA women and that these differences may be modified by tumor subtype and estrogen exposures. Future studies with a larger sample size may determine the full contribution of estrogen-related genes to racial/ethnic differences in breast cancer.

Associations between estrogen receptor-negative breast cancer and timing of reproductive events differ between African American and European American women.

The effects of reproductive factors on breast cancer risk seem to differ by estrogen receptor (ER) status. Menarche and first live birth (FLB) tend to occur at younger ages in African Americans (AA) than European Americans (EA), and could play a role in breast cancer disparities. In the Women's Circle of Health Study, a case-control study of breast cancer in EA and AA women, in-person interviews were conducted to collect epidemiologic data, including reproductive histories. Data on ER status, abstracted from pathology reports, were available for 814 AA and 538 EA breast cancer cases, and were analyzed with 1015 AA and 715 EA controls, to evaluate associations between subgroups and age at menarche, age at FLB, and the interval between those ages. Among AA women, later age at menarche (≥14 years) was associated with reduced risk of both ER(+) and ER(-) breast cancer, with ORs strongest for ER(-) disease [OR = 0.57; 95% confidence interval (CI), 0.37-0.88]; associations were weaker and nonsignificant for EA women. There were no significant associations with age at FLB, but AA women with a FLB within 15 years of menarche had increased risk of ER(-) disease (OR = 2.26; 95% CI, 1.29-3.95), with no significant associations among EAs. In our data, earlier age at menarche and shorter intervals until FLB are associated with ER(-) breast cancer in AA women; differential distributions by race of these and other reproductive risk factors could contribute to the higher prevalence of ER(-) breast cancer in AA women. Cancer Epidemiol Biomarkers Prev; 23(6); 1115-20. ©2014 AACR.

Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry.

Disparities in breast cancer biology are evident between American women of African ancestry (AA) and European ancestry (EA) and may be due, in part, to differences in immune function. To assess the potential role of constitutional host immunity on breast carcinogenesis, we tested associations between breast cancer risk and 47 single nucleotide polymorphisms (SNPs) in 26 cytokine-related genes of the adaptive immune system using 650 EA (n = 335 cases) and 864 AA (n = 458 cases) women from the Women's Circle of Health Study (WCHS). With additional participant accrual to the WCHS, promising SNPs from the initial analysis were evaluated in a larger sample size (1,307 EAs and 1,365 AAs). Multivariate logistic regression found SNPs in genes important for T helper type 1 (Th1) immunity (IFNGR2 rs1059293, IL15RA rs2296135, LTA rs1041981), Th2 immunity (IL4R rs1801275), and T regulatory cell-mediated immunosuppression (TGFB1 rs1800469) associated with breast cancer risk, mainly among AAs. The combined effect of these five SNPs was highly significant among AAs (P-trend = 0.0005). When stratified by estrogen receptor (ER) status, LTA rs1041981 was associated with ER-positive breast cancers among EAs and marginally among AAs. Only among AA women, IL15 rs10833 and IL15RA rs2296135 were associated with ER-positive tumors, and IL12RB1 rs375947, IL15 rs10833 and TGFB1 rs1800469 were associated with ER-negative tumors. Our study systematically identified genetic variants in the adaptive immune response pathway associated with breast cancer risk, which appears to differ by ancestry groups, menopausal status and ER status.

Associations of dietary folate, Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women.

African American (AA) women are more likely than European American (EA) women to be diagnosed with breast cancer at younger ages and to develop poor prognosis tumors. However, these racial differences are largely unexplained. Folate and other methyl-group nutrients may be related to breast carcinogenesis, but few studies have examined these associations in AA populations. We examined the associations of dietary intake of these nutrients with breast cancer risk overall, by menopausal and estrogen receptor (ER) status among 1,582 AA (749 cases) and 1,434 EA (744 cases) women using data from a case-control study, the Women's Circle of Health Study. Unconditional multivariable logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association of each nutrient and breast cancer risk. In AA women, inverse associations were observed for natural food folate intake among premenopausal women (fourth vs. first quartile: OR = 0.57, 95% CI, 0.33-1.00; p for trend = 0.06) and for ER-positive tumors (fourth vs. first quartile: OR = 0.58, 95% CI, 0.36-0.93; p for trend = 0.03), whereas in EA women, a positive association was observed for intake of synthetic folate (fourth vs. first quartile: OR = 1.53, 95% CI, 1.06-2.21; p for trend = 0.03). Our findings suggest that natural food folate intake is inversely associated with breast cancer risk and that this association may vary by race, menopausal status or ER status. The finding of an increased risk observed among EA women with the highest intake of synthetic folate from fortified foods warrants further investigation.

Parity and breastfeeding among African-American women: differential effects on breast cancer risk by estrogen receptor status in the Women's Circle of Health Study.

PURPOSE: It has long been held that parity reduces risk of breast cancer. However, accumulating evidence indicates that the effects of parity, as well as breastfeeding, may vary according to estrogen receptor (ER) status. We evaluated these associations in a case-control study among African-American women in New York City and New Jersey. METHODS: In the Women's Circle of Health Study, including 786 African-American women with breast cancer and 1,015 controls, data on reproductive histories were collected from in-person interviews, with tumor characteristics abstracted from pathology reports. We calculated number of live births and months breastfeeding for each child, and examined each in relation to breast cancer by ER status, and for triple-negative (TN) breast cancer. RESULTS: Although associations were not statistically significant, having children was associated with reduced risk of ER+ breast cancer [odds ratio (OR) 0.82, 95 % confidence interval (CI) 0.58-1.16], but increased risk of ER- tumors, with associations most pronounced for TN breast cancer (OR 1.81, 95 % CI 0.93-3.51). Breastfeeding gave no additional benefit for ER+ cancer, but reduced the risk of ER- disease associated with parity. CONCLUSIONS: Accumulating data from a number of studies, as well as our own in African-American women, indicate that the effects of parity and breastfeeding differ by ER status. African-American women are more likely to have children and not to breastfeed, and to have ER- and TN breast cancer. It is possible that breastfeeding in this population could reduce risk of more aggressive breast cancers.

Body fatness and breast cancer risk in women of African ancestry.

BACKGROUND: Obesity has been shown to be inversely associated with breast cancer risk in premenopausal women, while increasing risk in postmenopausal women. However, the current evidence is largely based on studies in Caucasian populations. Associations in women of African ancestry (AA), who have a higher prevalence of obesity, have been evaluated in few studies and results suggest different effects. METHODS: We evaluated the impact of body size, body fat distribution, and body composition on breast cancer risk among AA women (978 cases and 958 controls) participating in the Women's Circle of Health Study, a multi-site case-control study in New York City (NYC) and New Jersey (NJ). Cases were newly diagnosed with histologically confirmed ductal carcinoma in situ or invasive breast cancer, age 20-75 yrs. In NYC, cases were recruited through hospitals with the largest referral patterns for AA women and controls through random digit dialing (RDD). In NJ, cases were identified in seven counties in NJ thorough the NJ State Cancer Registry, and controls through RDD and community-based recruitment. During in-person interviews, questionnaires were administered and detailed anthropometric measurements were obtained. Body composition was assessed by bioelectrical impedance analysis. RESULTS: BMI did not have a major impact on pre- or post-menopausal breast cancer, but was significantly associated with reduced risk of ER-/PR- tumors among postmenopausal women (OR: 0.37; 95% CI: 0.15-0.96 for BMI > 30 vs. BMI < 25). Furthermore, increased premenopausal breast cancer risk was found for higher waist and hip circumferences after adjusting for BMI, with ORs of 2.25 (95% CI: 1.07-4.74) and 2.91 (95% CI: 1.39-6.10), respectively, comparing the highest vs. lowest quartile. While ORs for higher fat mass and percent body fat among postmenopausal women were above one, confidence intervals included the null value. CONCLUSIONS: Our study suggests that in AA women BMI is generally unrelated to breast cancer. However, higher waist and hip circumferences were associated with increased pre-menopausal breast cancer risk, while general obesity was associated with decreased risk of ER-/PR- tumors. Larger studies are needed to confirm findings and to evaluate the impact of obesity on breast cancer subtypes.

Body size in early life and breast cancer risk in African American and European American women.

PURPOSE: There is growing evidence that body size in early life influences lifetime breast cancer risk, but little is known for African American (AA) women. METHODS: We evaluated body size during childhood and young adulthood and breast cancer risk among 1,751 cases [979 AA and 772 European American (EA)] and 1,673 controls (958 AA and 715 EA) in the Women's Circle of Health Study. Odds ratio (OR) and 95 % confidence intervals (CI) were computed using logistic regression models while adjusting for potential covariates. RESULTS: Among AA women, being shorter at 7-8 years compared to peers was associated with increased postmenopausal breast cancer risk (OR 1.68, 95 % CI 1.02-2.74), and being heavier at menarche with decreased postmenopausal breast cancer risk, although of borderline significance (OR 0.45, 95 % CI 0.20-1.02). For EA women, being shorter from childhood through adolescence, particularly at menarche, was associated with reduced premenopausal breast cancer risk (OR 0.55, 95 % CI 0.31-0.98). After excluding hormone replacement therapy users, an inverse association with postmenopausal breast cancer was found among EA women reporting to be heavier than their peers at menarche (OR 0.18, 95 % CI 0.04-0.79). The inverse relationship between BMI at age 20 and breast cancer risk was stronger and only statistically significant in EA women. No clear association with weight gain since age 20 was found. CONCLUSIONS: Findings suggest that the impact of childhood height on breast cancer risk may differ for EA and AA women and confirm the inverse association previously reported in EA populations with adolescent body fatness, in AA women.

Racial disparities in red meat and poultry intake and breast cancer risk.

PURPOSE: Research on the role of red meat and poultry consumption in breast carcinogenesis is inconclusive, but the evidence in African-American (AA) women is lacking. The association between consuming meat and breast cancer risk was examined in the Women's Circle of Health Study involving 803 AA cases, 889 AA controls, 755 Caucasian cases, and 701 Caucasian controls. METHODS: Dietary information was collected using a Food Frequency Questionnaire. Odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models adjusting for potential covariates. RESULTS: Comparing the fourth versus the first quartiles, among Caucasian women, processed meat (OR = 1.48; 95 % CI 1.07-2.04), unprocessed red meat (OR = 1.40; 95 % CI 1.01-1.94), and poultry intakes (OR = 1.42; 95 % CI 1.01-1.99) increased breast cancer risk. Risk associated with poultry intake was more dominant in premenopausal women (OR = 2.33; 95 % CI 1.44-3.77) and for women with ER- tumors (OR = 2.55; 95 % CI 1.29-5.03) in the Caucasian group. Associations in AA women were mostly null except for a significant increased risk trend with processed meat consumption for ER+ tumors (OR = 1.36; 95 % CI 0.94-1.97, p trend = 0.04). CONCLUSIONS: Overall, associations between breast cancer risk and consumption of red meat and poultry were of different magnitude in AA and Caucasian women, with further differences noted by menopausal and hormone receptor status in Caucasian women. This is the first study to examine racial differences in meat and breast cancer risk and represents some of the first evidence in AA women.

Genetic variants in microRNAs and breast cancer risk in African American and European American women.

MicroRNAs (miRNAs) are an integral part of the post-transcriptional machinery of gene expression and have been implicated in the carcinogenic cascade. Single nucleotide polymorphisms (SNPs) in miRNAs and risk of breast cancer have been evaluated in populations of European or Asian ancestry, but not among women of African ancestry. Here we examined 145 SNPs in six miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and controls enrolled in the Women's Circle of Health Study. Allele frequencies of most SNPs (87 %) differed significantly by race. We found a number of SNPs in miRNAs and processing genes in association with breast cancer overall or stratified by estrogen receptor (ER) status. Several associations were significantly different by race, with none of the associations being significant in both races. Using a polygenic risk score to combine the effects of multiple SNPs, we found significant associations with the score in each subgroup analysis. For ER-positive cancer, each unit increment of the risk score was associated with a 51 % increased risk in AAs (OR = 1.51, 95 % CI = 1.30-1.74, p = 3.3 × 10(-8)) and a 73 % increased risk in EAs (OR = 1.73, 95 % CI = 1.45-2.06, p = 1.4 × 10(-9)). These data show, for the first time, that miRNA-related genetic variations may underlie the etiology of breast cancer in both populations of African and European ancestries. Future studies are needed to validate our findings and to explore the underlying mechanisms.

Innate immunity pathways and breast cancer Risk in African American and European-American women in the Women's Circle of Health Study (WCHS).

African American (AA) women are more likely than European American (EA) women to be diagnosed with early, aggressive breast cancer. Possible differences in innate immune pathways (e.g., inflammatory responses) have received little attention as potential mechanisms underlying this disparity. We evaluated distributions of selected genetic variants in innate immune pathways in AA and EA women, and examined their associations with breast cancer risk within the Women's Circle of Health Study (WCHS). In stage I of the study (864 AA and 650 EA women) we found that genotype frequencies for 35 of 42 tested SNPs (18 candidate genes) differed between AAs and EAs (corroborated by ancestry informative markers). Among premenopausal AA women, comparing variant allele carriers to non-carriers, reduced breast cancer risk was associated with CXCL5-rs425535 (OR=0.61, P=0.02), while among EA women, there were associations with TNFA-rs1799724 (OR =2.31, P =0.002) and CRP-rs1205 (OR=0.54, P=0.01). For postmenopausal women, IL1B-rs1143627 (OR=1.80, P=0.02) and IL1B-rs16944 (OR=1.85, P =0.02) were associated with risk among EA women, with significant associations for TNFA-rs1799724 limited to estrogen receptor (ER) positive cancers (OR=2.0, P =0.001). However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P0.0012 (0.05/42) except for TNFA-rs1799724 in ER positive cancers. In a stage II validation (1,365 AA and 1,307 EA women), we extended evaluations for four SNPs (CCL2-rs4586, CRP-rs1205, CXCL5-rs425535, and IL1RN-rs4251961), which yielded similar results. In summary, distributions of variants in genes involved in innate immune pathways were found to differ between AA and EA populations, and showed differential associations with breast cancer according to menopausal or ER status. These results suggest that immune adaptations suited to ancestral environments may differentially influence breast cancer risk among EA and AA women.

Rethinking sources of representative controls for the conduct of case-control studies in minority populations.

BACKGROUND: Recruitment of controls remains a challenge in case-control studies and particularly in studies involving minority populations. METHODS: We compared characteristics of controls recruited through random digit dialing (RDD) to those of community controls enrolled through churches, health events and other outreach sources among women of African ancestry (AA) participating in the Women's Circle of Health Study, a case-control study of breast cancer. Odds ratios and 95% confidence intervals were also computed using unconditional logistic regression to evaluate the impact of including the community controls for selected variables relevant to breast cancer and for which there were significant differences in distribution between the two control groups. RESULTS: Compared to community controls (n=347), RDD controls (n=207) had more years of education and higher income, lower body mass index, were more likely to have private insurance, and less likely to be single. While the percentage of nulliparous women in the two groups was similar, community controls tended to have more children, have their first child at a younger age, and were less likely to breastfeed their children. Dietary intake was similar in the two groups. Compared to census data, the combination of RDD and community controls seems to be more representative of the general population than RDD controls alone. Furthermore, the inclusion of the community group had little impact on the magnitude of risk estimates for most variables, while enhancing statistical power. CONCLUSIONS: Community-based recruitment was found to be an efficient and feasible method to recruit AA controls.

Supplement use during an intergroup clinical trial for breast cancer (S0221).

The use of supplements during chemotherapy is controversial, partly due to the potential effect of antioxidants on reduced efficacy of chemotherapy-related cytotoxicity. We examined supplement use among breast cancer patients registered to a clinical trial (SWOG 0221) before diagnosis and during treatment. Patients (n = 1,467) completed questionnaires regarding multivitamin and supplement use at trial registration (baseline) to capture use before diagnosis. Of these patients, 1,249 completed a 6-month followup questionnaire to capture use during treatment. We examined the use of vitamins C, D, E, B6, B12, folic acid, and calcium at these timepoints, as well as physician recommendations regarding supplement use. The use of vitamins C, E, folic acid, and calcium decreased during treatment, while the use of vitamin B6 increased. Five hundred seventy four patients (51 %) received no physician recommendations regarding supplement use. Among the remaining 49, 10 % were advised not to take multivitamins and/or supplements, 7 % were advised to use only multivitamins, and 32 % received recommendations to use multivitamins and/or supplements. Among patients who took vitamin C before diagnosis, those who were advised not to take supplements were >5 times more likely not to use of vitamin C during treatment than those not advised to stop use (OR = 5.27, 95 % CI 1.13-24.6). Previous non-users who were advised to take a multivitamin were nearly 5 times more likely to use multivitamins during treatment compared to those who received no recommendation (OR = 4.66, 95 % CI 2.10-10.3). In this clinical trial for high-risk breast cancer, supplement use generally decreased during treatment. Upon followup from the clinical trial, findings regarding supplement use and survival outcomes will better inform physician recommendations for patients on adjuvant chemotherapy.

Community-based partnership to identify keys to biospecimen research participation.

Reported barriers to participation in biospecimen banking include unwillingness to undergo blood-draw procedures and concerns about confidentiality breaches, privacy, and discrimination. The study identified key factors and influential perspectives to address these barriers and inform methods to improve recruitment and research participation among racially diverse community. A mixed-methods, community-based participatory research orientation was used to collect formative findings to develop a pilot intervention. Methods included nine key informant interviews, three focus groups (n = 26), and 64 community surveys. Findings showed: (1) increased concern of exploitation by pharmaceutical company sponsor; (2) varied perceptions about monetary compensation for research participation; and (3) willingness to participate in a biospecimen banking study by more than 30% of the people in the community survey. Research participation and biospecimen donation may be influenced by who is sponsoring a study. Monetary incentives for study participation may be more important for African American than White participants.

Pilot intervention outcomes of an educational program for biospecimen research participation.

Biospecimen banking programs are critically dependent on participation of diverse population members. The purpose of this study was to test a pilot intervention to enhance recruitment to a biospecimen bank among racially diverse community members. A mixed methods, community-based participatory research (CBPR) orientation was used to develop and pilot an intervention to educate and recruit participants to a biospecimen bank. Pre- and post-assessments of knowledge about research, perceived costs and benefits of participation (expected utility), and emotional states associated with research participation (affective associations) as well as post-intervention participation in biobanking were examined to determine intervention effectiveness. The pilot intervention educated 148 community members; 107 (73 %) donated blood and 77 (52 %) completed a 36-page lifestyle questionnaire. Thirty-two percent of participants were African American and 11 % were Native American. Participating in the educational program significantly reduced negative affect associated with research involving collection of genetic material or completion of a survey. Improved knowledge and understanding of biobanking and research through a CBPR approach are likely to increase participation rates in biobanking for diverse community members. Accurate information and improved knowledge can reduce individual anxiety and concerns that serve as barriers to research participation.

Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study.

INTRODUCTION: American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics. METHODS: In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status. RESULTS: More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs. CONCLUSIONS: These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women.

CAG repeat variants in the POLG1 gene encoding mtDNA polymerase-gamma and risk of breast cancer in African-American women.

The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA) women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls) who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49-6.21). Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies.