Susan L. Teitelbaum

The Long Island Breast Cancer Study Project: Description of a multi-institutional collaboration to identify environmental risk factors for breast cancer

The Long Island Breast Cancer Study Project is a federally mandated, population-based case-control study to determine whether breast cancer risk among women in the counties of Nassau and Suffolk, NY, is associated with selected environmental exposures, assessed by blood samples, self-reports, and environmental home samples. This report describes the collaborative projects background, rationale, methods, participation rates, and distributions of known risk factors for breast cancer by case-control status, by blood donation, and by availability of environmental home samples. Interview response rates among eligible cases and controls were 82.1% (n, = 1,508) and 62.8% (n = 1,556), respectively. Among case and control respondents who completed the interviewer-administered questionnaire, 98.2 and 97.6% self-completed the food frequency questionnaire; 73.0 and 73.3% donated a blood sample; and 93.0 and 83.3% donated a urine sample. Among a random sample of case and control respondents who are long-term residents, samples of dust (83.6 and 83.0%); soil (93.5 and 89.7%); and water (94.3 and 93.9%) were collected. Established risk factors for breast cancer that were found to increase risk among Long Island women include lower parity, late age at first birth, little or no breast feeding, and family history of breast cancer. Factors that were found to be associated with a decreased likelihood that a respondent would donate blood include increasing age and past smoking; factors associated with an increased probability include white or other race, alcohol use, ever breastfed, ever use of hormone replacement therapy, ever use of oral contraceptives, and ever had a mammogram. Long-term residents (defined as 15+ years in the interview home) with environmental home samples did not differ from other long-term residents, although there were a number of differences in risk factor distributions between long-term residents and other participants, as anticipated.

Weight Gain Prior to Diagnosis and Survival from Breast Cancer

Background: To examine the effects of prediagnostic obesity and weight gain throughout the life course on survival after a breast cancer diagnosis, we conducted a follow-up study among a population-based sample of women diagnosed with first, primary invasive, and in situ breast cancer between 1996 and 1997 (n = 1,508). Methods: In-person interviews were conducted shortly after diagnosis to obtain information on height and weight at each decade of life from age 20 years until 1 year before diagnosis. Patients were followed to determine all-cause (n = 196) and breast cancer–specific (n = 127) mortality through December 31, 2002. Results: In multivariate Cox proportional hazards models, obese women had increased mortality due to breast cancer compared with ideal weight women among those who were premenopausal at diagnosis [hazard ratio (HR), 2.85; 95% confidence interval (95% CI), 1.30-6.23] and postmenopausal at diagnosis (HR, 1.91; 95% CI, 1.06-3.46). Among women diagnosed with premenopausal breast cancer, those who gained >16 kg between age 20 years and 1 year before diagnosis, compared with those whose weight remained stable (±3 kg), had more than a 2-fold elevation in all-cause (HR, 2.45; 95% CI, 0.96-6.27) and breast cancer–specific mortality (HR, 2.09; 95% CI, 0.80-5.48). Women diagnosed with postmenopausal breast cancer who gained more than 12.7 kg after age of 50 years up to the year before diagnosis had a 2- to 3-fold increased risk of death due to all-causes (HR, 2.69; 95% CI, 1.63-4.43) and breast cancer (HR, 2.95; 95% CI, 1.36-6.43). Conclusions: These results indicate that high levels of prediagnostic weight and substantial weight gain throughout life can decrease survival in premenopausal and postmenopausal breast cancer patients. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1803–11)

Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island

Background: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. Methods: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n = 1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n = 173 deaths) and breast cancer–specific mortality (n = 113 deaths) were determined through the National Death Index. Results: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer–specific mortality only. Conclusion: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2285–92)

Vitamin and calcium supplement use is associated with decreased adenoma recurrence in patients with a previous history of neoplasia

INTRODUCTION: Although some have suggested that certain vitamins or calcium supplements may reduce adenoma recurrence, our own prior retrospective study found no such effects. The purpose of this case-control study was to further investigate whether regular vitamin or calcium supplement intake influenced the incidence of recurrent adenomatous polyps in patients with previous neoplasia who were undergoing follow-up colonoscopy. METHODS: This study enrolled 1,162 patients who underwent colonoscopy by one of three surgeons at Columbia-Presbyterian Medical Center in New York City between March 1993 and February 1997. Of these patients 448 (250 males) had a previous diagnosis of colorectal neoplasia (cancer, adenomas, or dysplasia). Of these, 183 (40.8 percent) had an adenoma at the index colonoscopy. Information was collected on personal and family history of colonic diseases, cigarette smoking, medication, and vitamin and micronutrient supplement usage on a questionnaire that was completed by the patients before the colonoscopy. Odds ratios were obtained by unconditional logistic regression analysis, adjusting for age and gender, and used adenoma recurrence at index colonoscopy as the outcome. RESULTS: The mean interval between colonoscopic examinations was 37 months for the recurrent adenoma group and 38 months for the nonrecurrent group of patients (P = not significant). In this case-control study we found a protective effect for the use of vitamin supplements in general (any vitamin) on the recurrence of adenomas (odds ratio, 0.41; 95 percent confidence interval, 0.27–0.61). Specifically, this protective effect was observed for the use of multivitamins (odds ratio, 0.47; 95 percent confidence interval, 0.31–0.72), vitamin E (odds ratio, 0.62; 95 percent confidence interval, 0.39–0.98), and for calcium supplementation (odds ratio, 0.51; 95 percent confidence interval, 0.27–0.96). Nonsignificant protective effects were noted for carotene/vitamin A, vitamin D, and vitamin C. CONCLUSIONS: The use of multivitamins, vitamin E, and calcium supplements were found to be associated with a lower incidence of recurrent adenomas in a population of patients with history of previous colonic neoplasia. Prospective, randomized trials are needed to better assess the impact of these agents and to determine whether the use of these supplements is associated with a protective effect against recurrent adenomas.

Immunohistochemical analysis of polycyclic aromatic hydrocarbon-DNA adducts in breast tumor tissue

Environmental carcinogens may play a role in the etiology of breast cancer, but the extent of their contribution is not yet defined. The aims of this study were to determine whether polycyclic aromatic hydrocarbon (PAH)-DNA adducts could be detected in stored paraffin blocks of breast tumor tissue (n=147) with an immunoperoxidase technique and whether they correlated with smoking history and/or mutant p53 protein expression. There was no significant difference in mean relative nuclear staining intensity in non-smokers (444+/-90, n=75), ever smokers (435+/-91, n=72), and current smokers (456+/-98, n=35). In either current or ever smokers, PAH-DNA adducts were non-significantly elevated in those with greater compared with lower exposure in relation to age at started smoking, years of smoking, cigarettes per day, and pack years. DNA damage levels were not elevated in tissues with compared with those without mutant p53 protein expression. These data demonstrate that immunohistochemical methods can be used to monitor DNA damage levels in archived breast tissues.

Abstract 2601: Polymorphisms in oxidative stress genes, physical activity and breast cancer risk

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILnnBACKGROUND. Reactive oxygen species (ROS) are known to react with DNA resulting in the transformation of normal epithelium to a malignant phenotype. While one functional variant in catalase (CAT) has been shown to be pertinent to breast cancer risk, few other polymorphisms in this gene have been assessed. Genetic variation in CAT or other genes in the oxidative stress pathway may mediate the carcinogenic effect of ROS produced by recreational physical activity (RPA) or result in adaptation of antioxidant capacity. METHODS. We investigated the association between three polymorphisms in CAT (rs4756146, rs2284365, rs480575) and breast cancer risk. We also characterized the joint effects of RPA with CAT, and with other functional oxidative stress variants (COMT, GPX, GSTA1, GSTM1, GSTP1, GSTT1, MnSOD, MPO, and UGT2B7) on breast cancer risk. Data were from the Long Island Breast Cancer Study Project, a population-based case-control study with interview and biomarker data available on 1102 cases and 1141 controls. Adjusted unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS. The presence of at least one CAT variant allele in rs4756146 was associated with a 23% decreased risk of postmenopausal breast cancer (95% CI=0.59-0.99). While rs2284365 and rs480575 were not associated with breast cancer risk, interaction between the two was evident on the multiplicative scale (likelihood ratio test p=0.087) indicating possible antagonism for these CAT polymorphisms. Further, upon combining the CAT genotypes, we observed a positive association between breast cancer risk and the number of putative high-risk alleles. Women with ≤ 4 high-risk alleles were at a 44% increased risk of breast cancer (95% CI=1.04-2.00) compared to women with ≤ 2 high-risk alleles. Finally, two polymorphisms (CAT rs1001179 and GSTP1 rs1695) among the oxidative stress genes considered were found to interact multiplicatively with postmenopausal RPA. Variant alleles in CAT antagonistically reversed the effect of high RPA on breast cancer risk (p=0.043) while variant alleles in GSTP1 synergistically enhanced the effect of low RPA on breast cancer risk (p=0.006). CONCLUSIONS. This study suggests that postmenopausal breast cancer risk may be decreased among women with one variant CAT allele in rs4756146. Risk may be elevated when considering combined effects of multiple high risk alleles in CAT. Variants in both CAT and GSTP1 may modify the association between RPA and breast cancer risk.nnCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2601. doi:1538-7445.AM2012-2601

Abstract P6-09-08: Exposure to multiple sources of polycyclic aromatic hydrocarbon and breast cancer incidence

Background. Previous epidemiologic studies, including our own, have consistently linked long-term exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to increased breast cancer incidence. It is unclear whether single sources, specific groups, or all PAH sources should be targeted for breast cancer risk reduction. This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures. Methods. In a population-based case-control study conducted on Long Island, New York (N=1,508 breast cancer cases/1,556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake. Results. Most women were exposed to PAHs from multiple sources. In a hierarchical model, breast cancer incidence was positively associated with ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.42) and residential synthetic firelog burning (OR=1.30, 95%CrI=1.06, 1.60). Additionally, PAH exposure groups, including ingestion (OR=1.45, 95%CrI=1.16, 1.79), indoor stove/fireplace use (OR=1.30, 95%CrI=1.02, 1.62), and total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.46, 95%CrI=1.03, 2.05), were associated with increased breast cancer incidence. Conclusions. Groups of PAH sources, especially those for ingestion and indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor. Citation Format: White AJ, Bradshaw PT, Herring AH, Teitelbaum SL, Beyea J, Stellman SD, Steck SE, Mordukhovich I, Eng SM, Engel LS, Conway K, Hatch M, Neugut AI, Santella RM, Gammon MD. Exposure to multiple sources of polycyclic aromatic hydrocarbon and breast cancer incidence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-08.

Abstract LB-290: The influence of body size and weight gain on global and gene promoter methylation in a population-based breast cancer study

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAnnPurpose. Little is known about how modifiable lifestyle factors, influence the epigenome. Elevated body mass index (BMI, weight kg/height m2) and adult weight gain are associated with increased risk of postmenopausal breast cancer, but the underlying mechanisms are not well understood. We hypothesized that these anthropometric factors may modify DNA methylation status by altering sex-steroid hormones levels and inflammatory markers.nnMethods. Resources from a population-based study (∼650 postmenopausal cases/∼650 postmenopausal controls) were used to construct logistic regression models. We explored potential modification of the global methylation-breast cancer association by BMI and weight gain using two assays: the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) in white blood cell DNA. Additionally, we estimated associations between anthropometrics and promoter methylation status in a panel of 13 breast cancer-related genes using ∼600 breast tumor tissues.nnResults. We observed a multiplicative interaction between LUMA and BMI (p=0.033) in relation to breast cancer. There was a greater than two-fold risk of postmenopausal breast cancer among women in the highest quartile of LUMA for each strata of BMI: age-adjusted odds ratios (95% confidence intervals) were 2.19(1.37, 3.52), 2.91(1.77, 4.80) and 2.51(1.45, 4.33) for women with BMI<25, BMI25-29.9 and BMI≥30, respectively. The observed estimates did not differ, statistically, across BMI categories. Additionally, we found no interactions with LINE-1 and observed no associations between anthropometrics and promoter methylation status in the genes examined.nnConclusions. Our data suggest that the association between BMI, weight gain and postmenopausal breast cancer may arise from mechanisms other than DNA methylation.nnCitation Format: Lauren E. McCullough, Jia Chen, Alexandra J. White, Xinran Xu, Yoon Hee Cho, Patrick T. Bradshaw, Sybil M. Eng, Susan L. Teitelbaum, Mary Beth Terry, Gail Garbowski, Alfred I. Neugut, Hanina Hibshoosh, Regina M. Santella, Marilie D. Gammon. The influence of body size and weight gain on global and gene promoter methylation in a population-based breast cancer study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-290. doi:10.1158/1538-7445.AM2014-LB-290

LIBCSP study area showing the major roads within an 80-km distance of Long Island from which vehicle emissions were tracked in this study

Copyright information: Taken from Validation and Calibration of a Model Used to Reconstruct Historical Exposurento Polycyclic Aromatic Hydrocarbons for Use in Epidemiologic StudiesEnvironmental Health Perspectives 2006;114(7):1053-1058.Published online 13 Mar 2006PMCID:PMC1513337.This is an Open Access article: verbatim copying and redistribution ofnthis article are permitted in all media for any purpose, provided thisnnotice is preserved along with the articles original DOI Studynparticipants were drawn from the shaded area, which is 150-km in lengthnand extends outward from New York City. The location of the U.S. EnvironmentalnProtection Agency carbon monoxide monitor is also indicated.

P4-12-03: Post-Diagnosis Weight Gain in Breast Cancer Survivors: When Should We Intervene?

Significance. Weight gain after breast cancer diagnosis is common and has been linked to poor prognosis. Studies of the etiology and longitudinal pattern of post-diagnosis weight gain are limited, yet are critical to developing effective prevention strategies to enhance ***survival.. Approach. We investigated the longitudinal pattern and determinants of post-diagnosis weight gain among 1,436 breast cancer survivors. The population-based cohort included women newly diagnosed with a first primary in situ or invasive breast cancer. Subjects were interviewed within 6 months of diagnosis and again 5 years later to ascertain factors related to survival, including self-reported anthropometric measures. We employed: adjusted random effects linear regression to identify factors related to weight change during the follow-up; multiple imputation to account for missing data; and Wald tests to test for significance of interactions with follow-up time. Results. Average weight gain was 0.74 kilograms (kg) during the first year after diagnosis and 2.39 kg at the follow-up interview. The strongest predictors of post-diagnosis gain were body size characteristics before diagnosis, which varied with time since diagnosis. Compared to women with body mass index (BMI, kg/m2) 18.5−24.9 1 year before diagnosis, those with greater BMI were more likely to gain weight during the first year after diagnosis [difference in mean yearly increase: BMI 25.0−29.9 vs. 18.5−24.9 (95% confidence interval): 1.93 kg/year (0.50, 3.37); BMI >=30.0 vs. 18.5−24.9: 0.47 kg/year (0.24, 0.71)] and after the first year [5.17 kg/year (3.68, 6.66) and 0.93 kg/year (0.58, 1.28), respectively], with the effect greater during the first year (p-interaction: Conclusions. Greater pre-diagnosis BMI and pre-diagnosis adult weight gain are strongly related to post-diagnosis weight gain among breast cancer survivors. The rate of post-diagnosis weight gain appears to be faster during the first year than after, suggesting that interventions to prevent post-diagnosis weight gain may be most important during the first year after diagnosis, especially among women who with BMI >= 25.0 1 year prior to diagnosis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-03.