Christine B Ambrosone

Publications (160)957.11 Total impact

• Article: Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers.

  Chi-Chen Hong, Song Yao, Susan E McCann, Ree Y Dolnick, Paul K Wallace, Zhihong Gong, Lei Quan, Kelvin P Lee, Sharon S Evans, Elizabeth A Repasky, Stephen B Edge, Christine B Ambrosone
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  ABSTRACT: Immune signatures in breast tumors differ by estrogen receptor (ER) status. The purpose of this study was to assess associations between ER phenotypes and circulating levels of cytokines that co-ordinate cell-mediated [T-helper type 1 (Th1)] and humoral [T-helper type 2 (Th2)] immunity. We conducted a case-case comparison of 523 women with newly diagnosed breast cancer to evaluate associations between 27 circulating cytokines, measured using Luminex XMap technology, and breast cancer phenotypes [ER(-) vs. ER(+); triple negative breast cancer (TNBC) vs. luminal A (LumA)]. Ratios of Th1 to Th2 cytokines were also evaluated. Levels of interleukin (IL)-5, a Th-2 cytokine, were higher in ER(-) than in ER(+) tumors. The highest tertile of IL-5 was more strongly associated with ER(-) (OR = 2.33, 95 % CI 1.40-3.90) and TNBCs (OR = 2.78, 95 % CI 1.53-5.06) compared to ER(+) and LumA cancers, respectively, particularly among premenopausal women (OR = 4.17, 95 % CI 1.86-9.34, ER(-) vs. ER(+); OR = 5.60, 95 % CI 2.09-15.01, TNBC vs. LumA). Elevated Th1 cytokines were also detected in women with ER(-) and TNBCs, with women in the highest tertile of interferon α2 (OR = 2.39, 95 % CI 1.31-4.35) or tumor necrosis factor-α (OR = 2.27, 95 % CI 1.21-4.26) being twice as likely to have TNBC versus LumA cancer. When cytokine ratios were examined, women with the highest ratios of Th1 cytokines to IL-5 levels were least likely to have ER(-) or TNBCs compared to ER(+) or LumA cancers, respectively. The strongest associations were in premenopausal women, who were up to 80 % less likely to have TNBC than LumA cancers (IL-12p40/IL-5, OR = 0.19, 95 % CI 0.07-0.56). These findings indicate that immune function is associated with ER(-) and TNBC and may be most relevant among younger women, who are likely to be diagnosed with these aggressive phenotypes.
  Breast Cancer Research and Treatment 04/2013; · 4.43 Impact Factor
• Article: Genome-wide association study of age at menarche in African-American women.

  Ellen W Demerath, Ching-Ti Liu, Nora Franceschini, Gary Chen, Julie R Palmer, Erin N Smith, Christina T L Chen, Christine B Ambrosone, Alice M Arnold, Elisa V Bandera, [......], B Gwen Windham, Melissa Wellons, Sarah S Murray, Michael Nalls, Aleksandar Rajkovic, Joel Hirschhorn, L Adrienne Cupples, Charles Kooperberg, Joanne M Murabito, Christopher A Haiman
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  ABSTRACT: African American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single nucleotide polymorphisms (SNPs) in a total of 18,089 AA women in 15 cohort studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2,850 women (Stage 2). First, while no SNP passed the pre-specified p< 5 x 10(-8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Second, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60%) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.
  Human Molecular Genetics 04/2013; · 7.64 Impact Factor
• Article: Serum Phospholipid Fatty Acids, Genetic Variation in Myeloperoxidase, and Prostate Cancer Risk in Heavy Smokers: A Gene-Nutrient Interaction in the Carotene and Retinol Efficacy Trial.

  Ting-Yuan David Cheng, Irena B King, Matt J Barnett, Christine B Ambrosone, Mark D Thornquist, Gary E Goodman, Marian L Neuhouser
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  ABSTRACT: The authors investigated associations of serum phospholipid n-3 and n-6 polyunsaturated fatty acids (PUFAs) and trans-fatty acids with prostate cancer risk, and whether myeloperoxidase G-463A (rs2333227) modified the associations in the Carotene and Retinol Efficacy Trial (CARET) (Seattle, Washington; Irvine, California; New Haven, Connecticut; San Francisco, California; Baltimore, Maryland; and Portland, Oregon, 1985-2003). Prerandomization sera were assayed for fatty acids among 641 men with incident prostate cancer (368 nonaggressive and 273 aggressive (stage III/IV or Gleason score ≥7)) and 1,398 controls. Overall, dihomo-γ-linolenic (quartiles 4 vs. 1: odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.49, 0.95; Ptrend = 0.024) and docosatetraenoic (OR = 0.69, 95% CI: 0.46, 1.02; Ptrend = 0.011) acids were inversely associated with nonaggressive and aggressive prostate cancer risks, respectively. Among men with MPO GG, the genotype upregulating oxidative stress, quartiles 4 versus 1 eicosapentaenoic plus docosahexaenoic acids were suggestively associated with an increased risk of aggressive prostate cancer (OR = 1.66, 95% CI: 0.95, 2.92; Ptrend = 0.07). However, the association was the inverse among men with MPO GA/AA genotypes (Pinteraction = 0.011). Interactions were also observed for docosapentaenoic acid, total n-3 PUFAs, and arachidonic acid. MPO GA/AA vs. GG was associated with a 2-fold increase in aggressive prostate cancer risk among men with low (quartile 1) n-3 PUFAs. This study adds important evidence linking oxidative stress with prostate carcinogenesis.
  American journal of epidemiology 03/2013; · 5.59 Impact Factor
• Source

  Available from: Irene Konstantopoulou

  Article: Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

  Montserrat Garcia-Closas, Fergus J Couch, Sara Lindstrom, Kyriaki Michailidou, Marjanka K Schmidt, Mark N Brook, Nick Orr, Suhn Kyong Rhie, Elio Riboli, Heather S Feigelson, [......], Alison M Dunning, Mark E Sherman, Georgia Chenevix-Trench, Stephen J Chanock, Per Hall, Paul D P Pharoah, Celine Vachon, Douglas F Easton, Christopher A Haiman, Peter Kraft
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  ABSTRACT: Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
  Nature Genetics 03/2013; 45(4):392-398. · 35.53 Impact Factor
• Article: Functional Variants at the 11q13 Risk Locus for Breast Cancer Regulate Cyclin D1 Expression through Long-Range Enhancers.

  Juliet D French, Maya Ghoussaini, Stacey L Edwards, Kerstin B Meyer, Kyriaki Michailidou, Shahana Ahmed, Sofia Khan, Mel J Maranian, Martin O'Reilly, Kristine M Hillman, [......], Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J Schoemaker, Bruce A J Ponder, Heli Nevanlinna, Melissa A Brown, Georgia Chenevix-Trench, Douglas F Easton, Alison M Dunning
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  ABSTRACT: Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.
  The American Journal of Human Genetics 03/2013; · 10.60 Impact Factor
• Source

  Available from: Grace Clarke Hillyer

  Article: Racial Disparities in Posttraumatic Stress After Diagnosis of Localized Breast Cancer: The BQUAL Study.

  Neomi Vin-Raviv, Grace Clarke Hillyer, Dawn L Hershman, Sandro Galea, Nicole Leoce, Dana H Bovbjerg, Lawrence H Kushi, Candyce Kroenke, Lois Lamerato, Christine B Ambrosone, Heidis Valdimorsdottir, Lina Jandorf, Jeanne S Mandelblatt, Wei-Yann Tsai, Alfred I Neugut
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  ABSTRACT: Background Little is known about the development of posttraumatic stress disorder (PTSD) over time among women diagnosed with breast cancer. This study examines changes in PTSD symptoms in the first 6 months after diagnosis and assesses racial/ethnic differences in PTSD symptomatology over time.Methods We recruited women with newly diagnosed breast cancer, stages I to III, from three sites in the United States. Three telephone interviews were conducted: baseline at about 2 to 3 months after diagnosis, first follow-up at 4 months after diagnosis, and second follow-up at 6 months after diagnosis. We measured traumatic stress in each interview using the Impact of Events Scale; recorded sociodemographic, tumor, and treatment factors; and used generalized estimating equations and polytomous logistic regression modeling to examine the associations between variables of interest and PTSD.ResultsOf 1139 participants, 23% reported symptoms consistent with a diagnosis of PTSD at baseline, 16.5% at first follow-up, and 12.6% at the second follow-up. Persistent PTSD was observed among 12.1% participants, as defined by having PTSD at two consecutive interviews. Among participants without PTSD at baseline, 6.6% developed PTSD at the first follow-up interview. Younger age at diagnosis, being black (odds ratio [OR] = 1.48 vs white, 95% confidence interval [CI] =1.04 to 2.10), and being Asian (OR = 1.69 vs white, 95% CI = 1.10 to 2.59) were associated with PTSD.Conclusions Nearly one-quarter of women newly diagnosed with breast cancer reported symptoms consistent with PTSD shortly after diagnosis, with increased risk among black and Asian women. Early identification of PTSD may present an opportunity to provide interventions to manage symptoms.
  CancerSpectrum Knowledge Environment 02/2013; · 14.07 Impact Factor
• Source

  Available from: Grace Clarke Hillyer

  Article: Racial Disparities in Post-traumatic Stress Following Diagnosis of Localized Breast Cancer: The BQUAL Study

  Neomi Vin-Raviv, Grace Clarke Hillyer, Dawn L. Hershman, Sandro Galea, Nicole Leoce, Dana H. Bovbjerg, Lawrence H. Kushi, Candyce Kroenke, Lois Lamerato, Christine B. Ambrosone, Heidis Valdimorsdottir, Lina Jandorf, Jeanne S. Mandelblatt, Wei-Yann Tsai, Alfred I. Neugut
  JNCI Journal of the National Cancer Institute 02/2013; · 13.76 Impact Factor
• Article: Supplement use during an intergroup clinical trial for breast cancer (S0221).

  Gary R Zirpoli, Patrick M Brennan, Chi-Chen Hong, Susan E McCann, Gregory Ciupak, Warren Davis, Joseph M Unger, G Thomas Budd, Dawn L Hershman, Halle C F Moore, James Stewart, Claudine Isaacs, Timothy Hobday, Muhammad Salim, Gabriel N Hortobagyi, Julie R Gralow, Kathy S Albain, Christine B Ambrosone
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  ABSTRACT: 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.
  Breast Cancer Research and Treatment 01/2013; · 4.43 Impact Factor
• Article: A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women.

  Chi Song, Gary K Chen, Robert C Millikan, Christine B Ambrosone, Esther M John, Leslie Bernstein, Wei Zheng, Jennifer J Hu, Regina G Ziegler, Sarah Nyante, [......], Stephen J Chanock, Peggy Wan, Xin Sheng, Loreall C Pooler, David J Van Den Berg, Loic Le Marchand, Laurence N Kolonel, Brian E Henderson, Chris A Haiman, Daniel O Stram
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  ABSTRACT: Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density.
  PLoS ONE 01/2013; 8(2):e57298. · 4.09 Impact Factor
• Source

  Available from: Grace Clarke Hillyer

  Article: Interpersonal influences and attitudes about adjuvant therapy treatment decisions among non-metastatic breast cancer patients: an examination of differences by age and race/ethnicity in the BQUAL study.

  Rachel C Shelton, Grace Clarke Hillyer, Dawn L Hershman, Nicole Leoce, Dana H Bovbjerg, Jeanne S Mandelblatt, Lawrence H Kushi, Lois Lamerato, S David Nathanson, Christine B Ambrosone, Alfred I Neugut
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  ABSTRACT: Patients are increasingly involved in cancer treatment decisions and yet little research has explored factors that may affect patient attitudes and beliefs about their therapeutic choices. This paper examines psychosocial factors (e.g., attitudes, social support), provider-related factors (e.g., communication, trust), and treatment considerations in a prospective study of a sample of non-metastatic breast cancer patients eligible for chemotherapy and/or hormonal therapy (BQUAL cohort). The data come from a multisite cohort study of white, black, Hispanic, and Asian non-metastatic breast cancer patients recruited in New York City, Northern California, and Detroit, Michigan. Baseline surveys were conducted over the telephone between 2006 and 2010 among a total of 1,145 women. Most participants were white (69 %), had more than a high school education (76 %), and were diagnosed with stage I disease (51 %). The majority of women reported discussing chemotherapy and hormonal therapy with their doctor (90 and 83 %, respectively); these discussions primarily took place with medical oncologists. Nearly a quarter of women reported that the treatment decision was difficult, and the majority were accompanied to the doctor (76 %) and involved a friend or family member in making the decision (54 %). Positive considerations (e.g., beliefs about treatment reducing risk of recurrence) were important in making treatment decisions. Participants preferred a shared decision-making style, but results suggested that there is room for improvement in terms of actual patient's involvement in making the decision and provider communication, particularly among black patients. Patients 65 years and older reported fewer provider discussions of chemotherapy, poorer patient-provider communication, higher rates of being assisted by family members in making the decision, and more negative attitudes and beliefs toward treatment.
  Breast Cancer Research and Treatment 12/2012; · 4.43 Impact Factor
• Article: OSAT: a tool for sample-to-batch allocations in genomics experiments.

  Li Yan, Changxing Ma, Dan Wang, Qiang Hu, Maochun Qin, Jeffrey M Conroy, Lara E Sucheston, Christine B Ambrosone, Candace S Johnson, Jianmin Wang, Song Liu
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  ABSTRACT: BACKGROUND: Batch effect is one type of variability that is not of primary interest but ubiquitous in sizable genomic experiments. To minimize the impact of batch effects, an ideal experiment design should ensure the even distribution of biological groups and confounding factors across batches. However, due to the practical complications, the availability of the final collection of samples in genomics study might be unbalanced and incomplete, which, without appropriate attention in sample-to-batch allocation, could lead to drastic batch effects. Therefore, it is necessary to develop effective and handy tool to assign collected samples across batches in an appropriate way in order to minimize batch effects. RESULTS: We describe OSAT (Optimal Sample Assignment Tool), a bioconductor package designed for automated sample-to-batch allocations in genomics experiments. CONCLUSIONS: OSAT is developed to facilitate the allocation of collected samples to different batches in genomics study. Through optimizing the even distribution of samples in groups of biological interest into different batches, it can reduce the confounding or correlation between batches and the biological variables of interest. It can also optimize the homogeneous distribution of confounding factors across batches. It can handle challenging instances where incomplete and unbalanced sample collections are involved as well as ideally balanced designs.
  BMC Genomics 12/2012; 13(1):689. · 4.07 Impact Factor
• Article: Robert C. Millikan: In Memoriam.

  Andrew F Olshan, Christine B Ambrosone, Jill S Barnholtz-Sloan, Marianne Berwick, Julie R Palmer, Nancy E Thomas
  Cancer Epidemiology Biomarkers &amp Prevention 12/2012; · 4.12 Impact Factor
• Article: Leveraging Epidemiology and Clinical Studies of Cancer Outcomes: Recommendations and Opportunities for Translational Research.

  Joanne W Elena, Lois B Travis, Naoko I Simonds, Christine B Ambrosone, Rachel Ballard-Barbash, Smita Bhatia, James R Cerhan, Patricia Hartge, Rebecca S Heist, Lawrence H Kushi, [......], John P Pierce, Leslie L Robison, Julia H Rowland, Deborah Schrag, Thomas A Sellers, Daniela Seminara, Xiao Ou Shu, Nancy E Thomas, Cornelia M Ulrich, Andrew N Freedman
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  ABSTRACT: As the number of cancer survivors continues to grow, research investigating the factors that affect cancer outcomes, such as disease recurrence, risk of second malignant neoplasms, and the late effects of cancer treatments, becomes ever more important. Numerous epidemiologic studies have investigated factors that affect cancer risk, but far fewer have addressed the extent to which demographic, lifestyle, genomic, clinical, and psychosocial factors influence cancer outcomes. To identify research priorities as well as resources and infrastructure needed to advance the field of cancer outcomes and survivorship research, the National Cancer Institute sponsored a workshop titled "Utilizing Data from Cancer Survivor Cohorts: Understanding the Current State of Knowledge and Developing Future Research Priorities" on November 3, 2011, in Washington, DC. This commentary highlights recent findings presented at the workshop, opportunities to leverage existing data, and recommendations for future research, data, and infrastructure needed to address high priority clinical and research questions. Multidisciplinary teams that include epidemiologists, clinicians, biostatisticians, and bioinformaticists will be essential to facilitate future cancer outcome studies focused on improving clinical care of cancer patients, identifying those at high risk of poor outcomes, and implementing effective interventions to ultimately improve the quality and duration of survival.
  CancerSpectrum Knowledge Environment 11/2012; · 14.07 Impact Factor
• Source

  Available from: Deborah O Erwin

  Dataset: Erwin 2012

  Warren Davis, Charles Walker, Gregory L Ciupak, Kirsten Moysich, Marc T Kiviniemi, Nikia Clark Hargrave, Frances G Saad-Harfouche, Deborah O Erwin, Christine B Ambrosone
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  Available from: Deborah O Erwin

  Article: Pilot Intervention Outcomes of an Educational Program for Biospecimen Research Participation.

  Marc T Kiviniemi, Frances G Saad-Harfouche, Gregory L Ciupak, Warren Davis, Kirsten Moysich, Nikia Clark Hargrave, Christine B Ambrosone, Charles Walker, Deborah O Erwin
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  ABSTRACT: 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.
  Journal of Cancer Education 11/2012; · 0.76 Impact Factor
• Article: Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African American women.

  Edward A Ruiz-Narváez, Lynn Rosenberg, Song Yao, Charles N Rotimi, L Adrienne Cupples, Elisa V Bandera, Christine B Ambrosone, Lucile L Adams-Campbell, Julie R Palmer
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  ABSTRACT: The rs2046210 single nucleotide polymorphism (SNP) in the 6q25.1 region was identified in a breast cancer genome-wide association study of Chinese women. The SNP has been replicated in European ancestry populations but replication efforts have failed in African ancestry populations. We evaluated a total of 13 tagging SNPs in the linkage disequilibrium block around rs2046210 in a case-control study of breast cancer nested within the Black Women's Health Study (BWHS), which included 1,191 cases and 1,941 controls. Replication of initial significant findings was carried out in 665 cases and 821 controls of African ancestry from the Women's Circle of Health Study (WCHS). No significant association was found for rs2046210 in univariate analysis. A new SNP, rs2046211, was significantly associated with reduced risk of breast cancer and was replicated in data from WCHS. In joint analyses that included both SNPs, the rs2046210-A allele was associated with increased risk of breast cancer (odds ratio = 1.14; 95% confidence interval = 1.02-1.28), and the rs2046211-G allele was associated with reduced risk (odds ratio = 0.80; 95% confidence interval = 0.67-0.95). Haplotype analysis confirmed these results and showed that the rs2046210-A allele is present in high-risk (rs2046211-C/rs2046210-A) and low-risk (rs2046211-G/rs2046210-A) haplotypes. Our results confirm the importance of 6q25.1 as a breast cancer susceptibility region. We replicated the rs2046210 association, after accounting for the haplotype background that included rs2046211 in African American women, and we report the presence of a novel signal that is tagged by rs2046211.
  Carcinogenesis 10/2012; · 5.70 Impact Factor
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  Available from: Grace Clarke Hillyer

  Article: A survey of breast cancer physicians regarding patient involvement in breast cancer treatment decisions.

  Grace Clarke Hillyer, Dawn L Hershman, Lawrence H Kushi, Lois Lamerato, Christine B Ambrosone, Dana H Bovbjerg, Jeanne S Mandelblatt, Sargam Rana, Alfred I Neugut
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  ABSTRACT: PURPOSE: Shared breast cancer treatment decision-making between patients and physicians increases patient treatment satisfaction and compliance and is influenced by physician-related factors. Attitudes and behaviors about patient involvement in breast cancer treatment decisions and treatment-related communication were assessed by specialty among breast cancer physicians of women enrolled in the Breast Cancer Quality of Care Study (BQUAL). RESULTS: Of 275 BQUAL physicians identified, 50.0% responded to the survey. Most physicians spend 46-60 min with the patient during the initial consult visit and 51.5% report that the treatment decision is made in one visit. Oncologists spend more time with new breast cancer patients during the initial consult (p = 0.021), and find it more difficult to handle their own feelings than breast surgeons (p = <0.001). CONCLUSION: Breast surgeons and oncologists share similar attitudes and behaviors related to patient involvement in treatment decision-making, yet oncologists report more difficulty managing their own feelings during the decision-making process.
  Breast (Edinburgh, Scotland) 10/2012; · 2.09 Impact Factor
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  Available from: Deborah O Erwin

  Article: Community-Based Partnership to Identify Keys to Biospecimen Research Participation.

  Deborah O Erwin, Kirsten Moysich, Marc T Kiviniemi, Frances G Saad-Harfouche, Warren Davis, Nikia Clark-Hargrave, Gregory L Ciupak, Christine B Ambrosone, Charles Walker
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  ABSTRACT: 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.
  Journal of Cancer Education 10/2012; · 0.76 Impact Factor
• Article: Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk.

  Lauren E McCullough, Regina M Santella, Rebecca J Cleveland, Patrick T Bradshaw, Robert C Millikan, Kari E North, Andrew F Olshan, Sybil M Eng, Christine B Ambrosone, Jiyoung Ahn, Susan E Steck, Susan L Teitelbaum, Alfred I Neugut, Marilie D Gammon
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  ABSTRACT: PURPOSE: The mechanisms driving the physical activity-breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity-breast cancer association. METHODS: We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls. RESULTS: Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59-0.99). We observed two statistical interactions between RPA and genes in the antioxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06-2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38-0.84). CONCLUSIONS: Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.
  Cancer Causes and Control 09/2012; · 2.88 Impact Factor
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  Available from: Grace Clarke Hillyer

  Article: Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study.

  Alfred I Neugut, Grace Clarke Hillyer, Lawrence H Kushi, Lois Lamerato, Nicole Leoce, S David Nathanson, Christine B Ambrosone, Dana H Bovbjerg, Jeanne S Mandelblatt, Carol Magai, Wei Yann Tsai, Judith S Jacobson, Dawn L Hershman
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  ABSTRACT: PURPOSEFor some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. PATIENTS AND METHODS We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years.ResultsOf 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor- and progesterone receptor-negative status) were associated with increased chemotherapy initiation. CONCLUSION Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.
  Journal of Clinical Oncology 09/2012; · 18.37 Impact Factor