Leslie Bernstein

Publications (328)2047.19 Total impact

• Article: Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status.

  Huiyan Ma, Yani Lu, Kathleen E Malone, Polly A Marchbanks, Dennis M Deapen, Robert Spirtas, Ronald T Burkman, Brian L Strom, Jill A McDonald, Suzanne G Folger, Michael S Simon, Jane Sullivan-Halley, Michael F Press, Leslie Bernstein
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  ABSTRACT: BACKGROUND: Black women are more likely than white women to have an aggressive subtype of breast cancer that is associated with higher mortality and this may contribute to the observed black-white difference in mortality. However, few studies have investigated the black-white disparity in mortality risk stratified by breast cancer subtype, defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Furthermore, it is not known whether additional consideration of p53 protein status influences black-white differences in mortality risk observed when considering subtypes defined by ER, PR and HER2 status. METHODS: Four biomarkers were assessed by immunohistochemistry in paraffin-embedded breast tumor tissue from 1,204 (523 black, 681 white) women with invasive breast cancer, aged 35--64 years at diagnosis, who accrued a median of 10 years' follow-up. Multivariable Cox proportional hazards regression models were fit to assess subtype-specific black-white differences in mortality risk. RESULTS: No black-white differences in mortality risk were observed for women with triple negative (ER-negative [ER-], PR-, and HER2-) subtype. However, older (50--64 years) black women had greater overall mortality risk than older white women if they had been diagnosed with luminal A (ER-positive [ER+] or PR+ plus HER2-) breast cancer (all-cause hazard ratio, HR, 1.88; 95% CI, 1.18 to 2.99; breast cancer-specific, HR, 1.51; 95% CI, 0.83 to 2.74). This black-white difference among older women was further confined to those with luminal A/p53- tumors (all-cause HR, 2.22; 95% confidence interval, CI, 1.30 to 3.79; breast cancer-specific HR, 1.89; 95% CI, 0.93 to 3.86). Tests for homogeneity of race-specific HRs comparing luminal A to triple negative subtype and luminal A/p53- to luminal A/p53+ subtype did not achieve statistical significance, although statistical power was limited. CONCLUSIONS: Our findings suggest that the subtype-specific black-white difference in mortality risk occurs mainly among older women diagnosed with luminal A/p53- breast cancer, which is most likely treatable. These results further suggest that factors other than subtype may be relatively more important in explaining the increased mortality risk seen in older black women.
  BMC Cancer 05/2013; 13(1):225. · 3.01 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: Childhood Infections and Adult Height in Monozygotic Twin Pairs.

  Amie E Hwang, Thomas M Mack, Ann S Hamilton, W James Gauderman, Leslie Bernstein, Myles G Cockburn, John Zadnick, Kristin A Rand, John L Hopper, Wendy Cozen
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  ABSTRACT: Adult height is determined by genetics and childhood nutrition, but childhood infections may also play a role. Monozygotic twins are genetically matched and offer an advantage when identifying environmental determinants. In 2005-2007, we examined the association of childhood infections with adult height in 140 height-discordant monozygotic twin pairs from the California Twin Program. To obtain information on childhood infections and growth, we interviewed the mothers of monozygotic twins who differed in self-reported adult height by at least 1-inch (2.5 cm). Within-pair differences in the relative frequency of childhood infections were highly correlated, especially within age groups. A conditional logistic regression analysis demonstrated that more reported episodes of febrile illness occurred in the twin with shorter stature (odds ratio = 2.00, 95% confidence interval: 1.18, 3.40). The association was strongest for differences in the relative frequency of infection during the toddler years (ages 1-5: odds ratio = 3.34, 95% confidence interval: 1.47, 7.59) and was similar when restricted to twin pairs of equal birth length. The association was not explained by differential nutritional status. Measures of childhood infection were associated with height difference in monozygotic twin pairs, independent of genome, birth length, and available measures of diet.
  American journal of epidemiology 04/2013; · 5.59 Impact Factor
• Article: Risk of colorectal cancer associated with active smoking among female teachers.

  Susan Hurley, Debbie Goldberg, David O Nelson, Yani Lu, Katherine Henderson, Leslie Bernstein, Peggy Reynolds
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  ABSTRACT: PURPOSE: The objective of this study was to examine the risk of colorectal cancer associated with active smoking among members of the California Teachers Study (CTS), a large cohort of female public school employees for whom highly detailed smoking information is available. METHODS: The analysis was conducted among the 122,264 CTS participants who lived in California at cohort entry in 1995/1996, had no prior history of colorectal cancer, and provided detailed smoking information. 1,205 cases of invasive colorectal cancer prospectively diagnosed in 1995-2009 were identified from the California Cancer Registry, including 650 in the proximal colon, 267 in the distal colon, and 288 in the rectum. Hazard ratios and 95 % confidence intervals were estimated using Cox proportional hazards models, stratified by age at cohort entry, and adjusted for race/ethnicity. RESULTS: Compared to never smokers, current smokers had an approximately 30 % increased risk of colorectal cancer. Overall, a slightly elevated risk was also noted for former smokers. Among former smokers, risks appeared to remain elevated for up to 20 years following cessation. Risks among former and current smokers increased with greater intensity and duration of smoking. Little evidence for heterogeneity in risk was noted for colon versus rectal cancer or for different subsites within the colon. CONCLUSIONS: These results provide convincing evidence that heavy and/or long-term smoking is a risk factor for cancers of the colon and rectum. Such evidence should be considered when updating screening guidelines to include targeting people with long active smoking histories.
  Cancer Causes and Control 04/2013; · 2.88 Impact Factor
• Article: Long-term physical activity trends in breast cancer survivors.

  Caitlin Mason, Catherine M Alfano, Ashley Wilder Smith, Ching-Yun Wang, Marian L Neuhouser, Catherine Duggan, Leslie Bernstein, Kathy B Baumgartner, Richard N Baumgartner, Rachel Ballard-Barbash, Anne McTiernan
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  ABSTRACT: BACKGROUND: Physical activity is associated with reduced mortality and higher quality of life in breast cancer survivors; however, limited data on the prevalence of activity and long-term trends after diagnosis are available. METHODS: A multi-ethnic cohort of 631 women (18-64 years) with stage 0-IIIA breast cancer were followed for 10 years. Recreational aerobic activity (MET-hrs/week) was ascertained for the year before diagnosis (baseline), 24 months, 5 and 10 years after enrollment. Women were classified according to U.S. physical activity guidelines (≥150 mins/week moderate or ≥75 mins/week vigorous activity). The odds ratios (OR) for meeting guidelines at 5 and 10 years according to baseline factors was estimated using logistic regression. The change in MET-hrs/wk was predicted using linear regression. RESULTS: Pre-diagnosis, 34% of women met physical activity guidelines; 34.0%, 39.5%, and 21.4% met guidelines at 24 months, 5 years, and 10 years post-enrollment, respectively. Fewer than 8% of survivors met guidelines at all follow-up periods. Over 10 years, recreational aerobic activity decreased by a mean(SD) 4.3(16.2) MET-hrs/wk. . Meeting guidelines pre-diagnosis was strongly associated with meeting guidelines at 5 years [OR (95% CI): 2.76 (1.85-4.1)] and 10 years [OR (95% CI): 3.35 (2.13-5.28)]. No other demographic or prognostic factors were significantly associated with the 10-year change in MET-hrs/wk. CONCLUSIONS: The majority of early breast cancer survivors do not meet national exercise recommendations 10 years post-diagnosis. Impact:Physical activity levels are low in breast cancer survivors across the 10 years post-diagnosis, yet the predictors of activity in this population remain poorly understood.
  Cancer Epidemiology Biomarkers &amp Prevention 04/2013; · 4.12 Impact Factor
• Article: Anthropometric, behavioral, and female reproductive factors and risk of multiple myeloma: a pooled analysis.

  Sophia S Wang, Jenna Voutsinas, Ellen T Chang, Christina A Clarke, Yani Lu, Huiyan Ma, Dee West, James V Lacey, Leslie Bernstein
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  ABSTRACT: BACKGROUND: Risk of developing multiple myeloma (MM) rises with age and is greater among men and blacks than among women and whites, respectively, and possibly increased among obese persons. Other risk factors remain poorly understood. By pooling data from two complementary epidemiologic studies, we assessed whether obesity, smoking, or alcohol consumption alters MM risk and whether female reproductive history might explain the lower occurrence of MM in females than in males. METHODS: The Los Angeles County MM Case-Control Study (1985-1992) included 278 incident cases and 278 controls, matched on age, sex, race, and neighborhood of residence at case's diagnosis. We estimated MM risk using conditional logistic regression to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). In the prospective California Teachers Study (CTS), 152 women were diagnosed with incident MM between 1995 and 2009; we calculated hazard ratios using Cox proportional hazards analysis. Data from the two studies were pooled using a stratified, nested case-control sampling scheme (10:1 match) for the CTS; conditional logistic regression among 430 cases and 1,798 matched controls was conducted. RESULTS: Obesity and smoking were not associated with MM risk in the individual or combined studies. Alcohol consumption was associated with decreased MM risk among whites only (pooled OR = 0.66, 95 % CI = 0.49-0.90) for ever versus never drinking. Higher gravidity and parity were associated with increased MM risk, with pooled ORs of 1.38 (95 % CI = 1.01-1.90) for ≥3 versus 1-2 pregnancies and 1.50 (95 % CI = 1.09-2.06) for ≥3 versus 1-2 live births. CONCLUSIONS: Female reproductive history may modestly alter MM risk, but appears unlikely to explain the sex disparity in incidence. Further investigation in consortial efforts is warranted.
  Cancer Causes and Control 04/2013; · 2.88 Impact Factor
• Article: Recent Physical Activity in Relation to DNA Damage and Repair Using the Comet Assay.

  Stephanie Whisnant Cash, A A Beresford S, Thomas L Vaughan, Patrick J Heagerty, Leslie Bernstein, Emily White, Marian Neuhouser
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  ABSTRACT: BACKGROUND: Limited evidence suggests that very high-intensity exercise is positively associated with DNA damage but moderate exercise may be associated with DNA repair. METHODS: Participants were 220 healthy, Washington State 50-76 year-olds in the validity/biomarker sub-study of the VITamins And Lifestyle (VITAL) cohort, who provided blood samples and completed questionnaires assessing recent physical activity and demographic and health factors. Measures included nested activity subsets: total activity, moderate- plus high-intensity activity, and high-intensity activity. DNA damage (n=122) and repair (n=99) were measured using the comet assay. Multivariate linear regression was used to estimate regression coefficients and associated 95% confidence intervals (CIs) for relationships between MET-hours per week of activity and each DNA outcome (damage, and 15- and 60-minute repair capacities). RESULTS: DNA damage was not associated with any measure of activity. However, 60-minute DNA repair was positively associated with both total activity (β=0.21, 95% CI: 0.0057, 0.412; p=0.044) and high-intensity activity (β=0.31, 95% CI: 0.20, 0.60; p=0.036), adjusting for age, sex, BMI, and current multivitamin use. CONCLUSIONS: This study is the first to assess broad ranges of activity intensity levels related to DNA damage and repair. Physical activity was unrelated to DNA damage but was associated with increased repair.
  Journal of Physical Activity and Health 04/2013;
• Source

  Available from: Stefan Nickels

  Article: Evidence of Gene–Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors

  Stefan Nickels, Thérèse Truong, Rebecca Hein, Kristen Stevens, Katharina Buck, Sabine Behrens, Ursula Eilber, Martina Schmidt, Lothar Häberle, Alina Vrieling, [......], Alice J. Sigurdson, Michele M. Doody, Pascal Guénel, Paul D. P. Pharoah, Marjanka K. Schmidt, Per Hall, Doug F. Easton, Montserrat Garcia-Closas, Roger L. Milne, Jenny Chang-Claude
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  ABSTRACT: Author Summary Breast cancer involves combined effects of numerous genetic, environmental, and behavioral risk factors that are unique to each individual. High risk genes, such as BRCA1 and BRCA2 , account for only a small proportion of disease occurrence. Recent genome-wide research has identified more than 20 common genetic variants, which individually alter breast cancer risk very moderately. We undertook an international collaborative study to determine whether the effect of these genetic variants vary with environmental factors, such as parity, body mass index (BMI), height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, and physical activity, which are known to affect risk of developing breast cancer. Using pooled data from 24 studies of the Breast Cancer Association Consortium (BCAC), we provide first convincing evidence that the breast cancer risk associated with a genetic variant in LSP1<
  PLoS Genet. 03/2013; 9(3):e1003284.
• 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
• Source

  Available from: Stefan Nickels

  Article: Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors.

  Stefan Nickels, Thérèse Truong, Rebecca Hein, Kristen Stevens, Katharina Buck, Sabine Behrens, Ursula Eilber, Martina Schmidt, Lothar Häberle, Alina Vrieling, [......], Alice J Sigurdson, Michele M Doody, Pascal Guénel, Paul D P Pharoah, Marjanka K Schmidt, Per Hall, Doug F Easton, Montserrat Garcia-Closas, Roger L Milne, Jenny Chang-Claude
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  ABSTRACT: Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4×10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1×10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3×10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.
  PLoS Genetics 03/2013; 9(3):e1003284. · 8.69 Impact Factor
• Article: Increased long-term recreational physical activity is associated with older age at natural menopause among heavy smokers: the California Teachers Study.

  Aina Emaus, Christina Dieli-Conwright, Xinxin Xu, James V Lacey, Sue A Ingles, Peggy Reynolds, Leslie Bernstein, Katherine D Henderson
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  ABSTRACT: Although physical activity modulates the hypothalamic-pituitary-ovarian axis, the few studies that have investigated whether physical activity is associated with age at natural menopause have yielded mixed results. We set out to determine whether physical activity is associated with the timing of natural menopause in a large cohort of California women overall and by smoking history. We investigated the association between long-term physical activity (h/wk/y) and age at natural menopause among 97,945 women in the California Teachers Study. Multivariable Cox proportional hazards regression methods were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The impact of cigarette smoking (never smoker, former light smoker, former heavy smoker, current light smoker, and current heavy smoker) as an effect modifier was evaluated. In a multivariable model adjusted for body mass index at age 18 years, age at menarche, race/ethnicity, and age at first full-term pregnancy, increased physical activity was statistically significantly associated with older age at natural menopause (Ptrend = 0.005). Higher body mass index at age 18 years (Ptrend = 0.0003) and older age at menarche (Ptrend = 0.0003) were also associated with older age at natural menopause. Hispanic ethnicity (vs non-Hispanic whites; HR, 1.17; 95% CI, 1.09-1.26), current smokers (vs never smokers; HR, 1.68; 95% CI, 1.60-1.75 for current light smokers; HR, 1.38; 95% CI, 1.33-1.44 for current heavy smokers), and older age at first full-term pregnancy (HR≥29, 2+ full-term pregnancies vs HR<29, 2+ full-term pregnancies, 1.10; 95% CI, 1.06-1.14) were associated with earlier age at natural menopause. Upon stratification by smoking history, increased physical activity was statistically significantly associated with older age at natural menopause among heavy smokers only (HRhighest quartile vs HRlowest quartile, 0.88; 95% CI, 0.81-0.97; Ptrend = 0.02 for former heavy smokers; HRhighest quartile vs HRlowest quartile, 0.89; 95% CI, 0.80-0.99; Ptrend = 0.04 for current heavy smokers). Age at natural menopause is a complex trait; the determinants of age at natural menopause, including physical activity, may differ by smoking status.
  Menopause (New York, N.Y.) 03/2013; 20(3):282-90. · 3.08 Impact Factor
• Article: Sedentary behavior, health-related quality of life, and fatigue among breast cancer survivors.

  Stephanie M George, Catherine M Alfano, Ashley Wilder Smith, Melinda L Irwin, Anne McTiernan, Leslie Bernstein, Kathy B Baumgartner, Rachel Ballard-Barbash
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  ABSTRACT: Background: Many cancer survivors experience declines in health-related quality of life (HRQOL) and increases in fatigue as a result of cancer and its treatment. Exercise is linked to improvements in these outcomes, but little is known about the role of sedentary behavior. In a large, ethnically-diverse cohort of breast cancer survivors, we examined the relationship between sedentary time, HRQOL, and fatigue, and examined if that relationship differed by recreational moderate-vigorous physical activity (MVPA) level. Methods: Participants were 710 women diagnosed with stage 0-IIIA breast cancer in the Health, Eating, Activity, and Lifestyle Study. Women completed questionnaires at approximately 30-months postdiagnosis (sedentary time; recreational MVPA) and 41-months postdiagnosis (HRQOL; fatigue). In multivariate models, we regressed these outcomes linearly on quartiles of daily sedentary time, and a variable jointly reflecting sedentary time quartiles and MVPA categories (0; >0 to <9; ≥9 MET-hrs/wk). Results: Sedentary time was not independently related to subscales or summary scores of HRQOL or fatigue. In addition, comparisons of women with high vs. low (Q4:Q1) sedentary time by MVPA level did not result in significant differences in HRQOL or fatigue. Conclusion: In this breast cancer survivor cohort, self-reported sedentary time was not associated with HRQOL or fatigue, 3.5 years postdiagnosis.
  Journal of Physical Activity and Health 03/2013; 10(3):350-8.
• Article: Deriving clinically meaningful cut-scores for fatigue in a cohort of breast cancer survivors: a Health, Eating, Activity, and Lifestyle (HEAL) Study.

  Angela M Stover, Bryce B Reeve, Barbara F Piper, Catherine M Alfano, Ashley Wilder Smith, Sandra A Mitchell, Leslie Bernstein, Kathy B Baumgartner, Anne McTiernan, Rachel Ballard-Barbash
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  ABSTRACT: PURPOSE: To empirically determine clinically meaningful cut-scores on the 0-10 response scale of the revised Piper Fatigue Scale (PFS-R) and its shorter version (PFS-12). Breast cancer survivors were classified (i.e., none, mild, moderate, or severe fatigue) based on the cut-scores, and relationships between these cut-scores and decrements in health-related quality of life (HRQOL) were examined. METHODS: A total of 857 breast cancer survivors, stages in situ-IIIa, from the Health, Eating, Activity, and Lifestyle (HEAL) Study were eligible. Survivors completed the PFS-R, SF-36, and a sexual health scale approximately 3 years after diagnosis. Multivariate analysis of covariance was used to examine five fatigue severity cut-score models, controlling for demographics, clinical characteristics, comorbidity, and antidepressant use. Multivariate regression was used to examine HRQOL decrements by cut-score category. RESULTS: Analyses supported two similar fatigue severity cut-score models for the PFS-R and PFS-12: Model A.) none (0), mild (1-3), moderate (4-6), and severe (7-10); and Model D.) none (0), mild (1-2), moderate (3-5), and severe (6-10). For every threshold increase in fatigue severity, clinically meaningful decrements in physical, mental, and sexual health scores were observed, supporting construct validity of the fatigue cut-scores. CONCLUSION: Standardized fatigue cut-scores may enhance interpretability and comparability across studies and populations and guide treating planning.
  Quality of Life Research 02/2013; · 2.30 Impact Factor
• Article: Invited Commentary: Reproductive Organ Surgeries and Breast Cancer Risk--Apples, Oranges, or Fruit Cocktail?

  David J Press, Leslie Bernstein
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  ABSTRACT: Case-control and cohort studies are almost always complicated by nonrandom exposure allocation, which must be minimized in the design and analysis phases. Tubal sterilization is a common gynecological procedure that may be associated with other reproductive organ surgeries, which in turn may be associated with breast cancer risk. In this issue of the Journal, Gaudet et al. (Am J Epidemiol. 2013;000(00)000-000) argue successfully that tubal sterilization is unassociated with breast cancer risk. Scrutiny of the heterogeneous studies included in their meta-analysis underscores the role of confounding and effect modification in observational epidemiologic studies. Specifically, tubal sterilization is unassociated with breast cancer risk, but either oophorectomy or hysterectomy, or both, and the timing of these procedures warrant careful consideration in the design, analysis, and interpretation of observational research on reproductive factors.
  American journal of epidemiology 02/2013; · 5.59 Impact Factor
• Article: The association between television watching time and all-cause mortality after breast cancer.

  Stephanie M George, Ashley W Smith, Catherine M Alfano, Heather R Bowles, Melinda L Irwin, Anne McTiernan, Leslie Bernstein, Kathy B Baumgartner, Rachel Ballard-Barbash
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  ABSTRACT: PURPOSE: Sedentary time is a rapidly emerging independent risk factor for mortality in the general population, but its prognostic effect among cancer survivors is unknown. In a multiethnic, prospective cohort of breast cancer survivors, we hypothesized that television watching time would be independently associated with an increased risk of death from any cause. METHODS: The Health, Eating, Activity, and Lifestyle Study cohort included 687 women diagnosed with local or regional breast cancer. On average 30 (±4) months postdiagnosis, women completed self-report assessments on time spent sitting watching television/videos in a typical day in the previous year. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for death from any cause (n = 89) during the 7 years of follow-up. RESULTS: Television time (top tertile vs. bottom tertile) was positively related to risk of death (HR, 1.94; 95 % CI, 1.02, 3.66, p (trend) = 0.024), but the association was attenuated and not statistically significant after adjustment for aerobic moderate-vigorous intensity physical activity (HR, 1.70; 95 % CI, 0.89, 3.22, p (trend) = 0.14) and all covariates (HR, 1.39; 95 % CI, 0.69, 2.82, p (trend) = 0.48). CONCLUSION: In this first published investigation on this topic, we did not observe a statistically significant multivariate-adjusted association between television watching time and risk of death among women diagnosed with breast cancer. IMPLICATIONS FOR CANCER SURVIVORS: These results begin an evidence base on this topic that can be built upon to inform lifestyle recommendations for this expanding, aging population.
  Journal of Cancer Survivorship 02/2013; · 2.63 Impact Factor
• Article: Associations of serum 25-hydroxyvitamin D with overall and breast cancer-specific mortality in a multiethnic cohort of breast cancer survivors.

  Adriana Villaseñor, Rachel Ballard-Barbash, Anita Ambs, Leslie Bernstein, Kathy Baumgartner, Richard Baumgartner, Cornelia M Ulrich, Bruce W Hollis, Anne McTiernan, Marian L Neuhouser
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  ABSTRACT: PURPOSE: Despite limited evidence on the association of vitamin D with outcomes in breast cancer survivors, some clinicians advise breast cancer patients to use vitamin D supplements. More evidence is needed to inform these recommendations. METHODS: In the Health, Eating, Activity, and Lifestyle study, we examined associations of post-treatment serum concentrations of 25-hydroxyvitamin D (25(OH)D) on overall and breast cancer-specific mortality in 585 breast cancer survivors from western Washington State, New Mexico, and Los Angeles County. 25(OH)D was measured in stored blood collected 2 years post-enrollment. Outcomes were ascertained from the Surveillance, Epidemiology, and End Results registries and medical records. Cox proportional hazards models were fit to assess associations of serum 25(OH)D with overall and breast cancer-specific mortality. RESULTS: After a median follow-up of 9.2 years; 110 women died, including 48 from breast cancer. Standard cut points classified 211 (31.6 %) women as serum 25(OH)D deficient (<20 ng/mL), 189 (32.2 %) as insufficient (20-30 ng/mL), and 185 (36.2 %) as sufficient (>30 ng/mL). Compared to women with deficient 25(OH)D, those in the sufficient ranges had a decreased risk of overall mortality (age-adjusted HR = 0.58; 95 % CI 0.36-0.96); however, multivariate adjustments attenuated the association (HR = 0.90; 95 % CI 0.50-1.61). No association was found between serum 25(OH)D and breast cancer-specific mortality (sufficient: HR = 1.21; 95 % CI 0.52-2.80) in multivariate models. CONCLUSION: In this breast cancer cohort, higher serum 25(OH)D may be associated with improved survival, but results were not statistically significant and must be interpreted with caution. The potential prognostic effect of vitamin D from diet, supplements, or both should be evaluated in future larger studies with additional endpoints from breast cancer patients.
  Cancer Causes and Control 01/2013; · 2.88 Impact Factor
• Article: Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status.

  Seungyoun Jung, Donna Spiegelman, Laura Baglietto, Leslie Bernstein, Deborah A Boggs, Piet A van den Brandt, Julie E Buring, James R Cerhan, Mia M Gaudet, Graham G Giles, [......], Schoichiro Tsugane, Kala Visvanathan, Elisabete Weiderpass, Walter C Willett, Alicja Wolk, Anne Zeleniuch-Jacquotte, Shumin M Zhang, Xuehong Zhang, Regina G Ziegler, Stephanie A Smith-Warner
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  ABSTRACT: Background Estrogen receptor-negative (ER(-)) breast cancer has few known or modifiable risk factors. Because ER(-) tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER(-) breast cancer.Methods Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER(+)) and 4821 ER(-) breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided.ResultsTotal fruit and vegetable intake was statistically significantly inversely associated with risk of ER(-) breast cancer but not with risk of breast cancer overall or of ER(+) tumors. The inverse association for ER(-) tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER(-) breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER(+) breast cancer (P (common-effects) by ER status < .001). Total fruit consumption was non-statistically significantly associated with risk of ER(-) breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04).Conclusions We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER(-) breast cancer in our large pooled analyses.
  CancerSpectrum Knowledge Environment 01/2013; · 14.07 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
• Article: Variants in tamoxifen metabolizing genes: a case-control study of contralateral breast cancer risk in the WECARE study.

  Jennifer D Brooks, Sharon N Teraoka, Kathleen E Malone, Robert W Haile, Leslie Bernstein, Charles F Lynch, Lene Mellemkjær, David J Duggan, Anne S Reiner, Patrick Concannon, Katherine Schiermeyer, Juan Pablo Lewinger, Jonine L Bernstein, Jane C Figueiredo
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  ABSTRACT: Tamoxifen has been shown to greatly reduce risk of recurrence and contralateral breast cancer (CBC). Still, second primary contralateral breast cancer is the most common malignancy to follow a first primary breast cancer. Genetic variants in CYP2D6 and other drug-metabolizing enzymes that alter the metabolism of tamoxifen may be associated with CBC risk in women who receive the drug. This is the first study to investigate the impact of this variation on risk of CBC in women who receive tamoxifen. From the population-based Women's Environment Cancer and Radiation Epidemiology (WECARE) Study, we included 624 Caucasian women with CBC (cases) and 1,199 women with unilateral breast cancer (controls) with complete information on tumor characteristics and treatment. Conditional logistic regression was used to assess the risk of CBC associated with 112 single nucleotide polymorphisms (SNPs) in 8 genes involved in the metabolism of tamoxifen among tamoxifen users and non-users. After adjustment for multiple testing, no significant association was observed between any of the genotyped variants and CBC risk in either tamoxifen users or non-users. These results suggest that when using a tagSNP approach, common variants in selected genes involved in the metabolism of tamoxifen are not associated with risk of CBC among women treated with the drug.
  International Journal of Molecular Epidemiology and Genetics 01/2013; 4(1):35-48.
• Article: Household endotoxin levels and the risk of non-Hodgkin lymphoma.

  Jun Wang, Wendy Cozen, Peter S Thorne, Kiros Berhane, James R Cerhan, Patricia Hartge, Mary H Ward, Anneclaire J De Roos, Richard K Severson, Lindsay M Morton, Leslie Bernstein, Martha S Linet, Joanne S Colt
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  ABSTRACT: OBJECTIVE: Endotoxin, a component of the outer membrane of gram-negative bacteria, elicits a strong innate and inflammatory immune response associated with the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Because TNF-α polymorphisms that increase TNF-α production are associated with an increased risk of non-Hodgkin lymphoma (NHL), we hypothesized that increased levels of household endotoxin would be associated with an increased NHL risk. METHODS: We evaluated this association in the National Cancer Institute/Surveillance, Epidemiology and End Results (NCI/SEER) NHL multicenter population-based case-control study. Used vacuum cleaner bags were collected from participants during a home interview. Dust samples from the bags of 594 cases and 442 controls were analyzed for endotoxin [endotoxin unit (EU)/mg of dust] using the kinetic chromogenic Limulus amebocyte lysate assay. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for age, sex, race, education, study center, and farm exposure. RESULTS: Endotoxin was not associated with NHL overall [odds ratio (OR) for highest quartile of endotoxin levels = 0.81, 95 % confidence interval (CI) = 0.55, 1.20; p for trend = 0.35] or with diffuse large B-cell lymphoma (OR = 0.63, 95 % CI = 0.34, 1.16; p = 0.31) or follicular lymphoma (OR = 1.07, 95 % CI = 0.61, 1.89; p = 0.73) subtypes. Both working and living on a farm were associated with higher household endotoxin levels compared to never working (p = 0.009) or living (p = 0.01) on a farm. Excluding farmers from the analysis did not change the results. CONCLUSIONS: We found no evidence of a role for household endotoxin in NHL etiology.
  Cancer Causes and Control 01/2013; · 2.88 Impact Factor