Showing papers by "Cynthia A. Thomson published in 2016"

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

Abstract: Diet is a modifiable factor associated with the risk of several cancers, with convincing evidence showing a link between diet and breast cancer. The role of bioactive compounds of food origin, including those found in cruciferous vegetables, is an active area of research in cancer chemoprevention. This review focuses on 3,3′-diindolylmethane (DIM), the major bioactive indole in crucifers. Research of the cancer-preventive activity of DIM has yielded basic mechanistic, animal, and human trial data. Further, this body of evidence is largely supported by observational studies. Bioactive DIM has demonstrated chemopreventive activity in all stages of breast cancer carcinogenesis. This review describes current evidence related to the metabolism and mechanisms of DIM involved in the prevention of breast cancer. Importantly, this review also focuses on current evidence from human observational and intervention trials that have contributed to a greater understanding of exposure estimates that will inform recommendations for DIM intake.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial

Abstract: Background While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. Methods The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. Results After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). Conclusion In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Diet Quality and Colorectal Cancer Risk in the Women's Health Initiative Observational Study.

Abstract: Diet quality index scores on Healthy Eating Index 2010 (HEI-2010), Alternative HEI-2010, alternative Mediterranean Diet Index, and the Dietary Approaches to Stop Hypertension (DASH) index have been inversely associated with all-cause and cancer-specific death. This study assessed the association between these scores and colorectal cancer (CRC) incidence as well as CRC-specific mortality in the Women's Health Initiative Observational Study (1993-2012), a US study of postmenopausal women. During an average of 12.4 years of follow-up, there were 938 cases of CRC and 238 CRC-specific deaths. We estimated multivariate hazard ratios and 95% confidence intervals for relationships between quintiles of diet scores (from baseline food frequency questionnaires) and outcomes. HEI-2010 score (hazard ratios were 0.81, 0.77, and 0.73 with P values of 0.04, 0.01, and <0.01 for quintiles 3-5 vs. quintile 1, respectively) and DASH score (hazard ratios were 0.72, 0.74, and 0.78 with P values of <0.01, <0.01, and 0.03 for quintiles 3-5 vs. quintile 1, respectively), but not other diet scores, were associated with a lower risk of CRC in adjusted models. No diet scores were significantly associated with CRC-specific mortality. Closer adherence to HEI-2010 and DASH dietary recommendations was inversely associated with risk of CRC in this large cohort of postmenopausal women.

Body shape, adiposity index, and mortality in postmenopausal women: Findings from the Women's Health Initiative

Abstract: Objective Studies evaluating the relationship between body mass index (BMI) and mortality demonstrate a U-shaped association. To expand, this study evaluated the relationship between adiposity indices, a body shape index (ABSI) and body adiposity index (BAI), and mortality in 77,505 postmenopausal women. Methods A prospective cohort analysis was conducted in the Women's Health Initiative to ascertain the independent relationships between adiposity indices and mortality in order to inform on the clinical usefulness of alternate measures of mortality risk. ABSI (waist circumference (cm)/[BMI2/3 × height (cm)1/2]), BAI (hip circumference (cm)/[height (m)1.5] - 18), weight, BMI, and waist circumference (WC) were evaluated in relation to mortality risk using adjusted Cox proportional hazards regression models. Results ABSI showed a linear association with mortality (HR, 1.37; 95% CI, 1.28-1.47 for quintile 5 vs. 1) while BMI and BAI had U-shaped relationships with HR of 1.30; 95% CI, 1.20-1.40 for obesity II/III BMI and 1.06, 95% CI, 0.99-1.13 for BAI. Higher WC (HR, 1.21; 95% CI, 1.13-1.29 for quintile 5 vs. 1) showed relationships similar to BMI. Conclusions ABSI appears to be a clinically useful measure for estimating mortality risk, perhaps more so than BAI and BMI in postmenopausal women.

Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol

Abstract: Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases. ClinicalTrials.gov Identifier: NCT02028221 . Registered on January 2, 2014. Grant #: 1R01CA172444-01A1 awarded on Sept 11, 2013.

Evaluating Latino WIC Mothers' Perceptions of Infant's Healthy Growth: A Formative Assessment.

Abstract: Objectives This article reports on a formative assessment with Latino mothers in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) evaluating knowledge, attitudes and behaviors regarding healthy growth for infants and their understanding of infant growth monitoring. Further, we explored the acceptability and feasibility of mothers’ monitoring their infants’ growth. This assessment includes healthy growth perceptions from mothers, caregivers and from WIC staff. Methods Utilizing a mixed method approach, this assessment included qualitative focus groups with WIC mothers that included a growth chart plotting exercise and a quantitative survey. In-depth interviews with clinic staff discussing protocols used in assessing children’s growth were also conducted in one WIC clinic. Results Focus group participants included 34 mothers and 19 caregivers with a mean age of 32 years; 90 % identified as Latino. Themes included concern for underweight status, and reports of limited conversations between mothers and healthcare providers regarding overweight status, and infant feeding practices/beliefs that may contribute to feeding behaviors associated with risk for excess weight gain during infancy. Growth charts were well received, mothers were able to plot with modest accuracy; but effectiveness of growth plotting might be limited without refinement for health literacy and the provision of culturally-sensitive education in relation to feeding behaviors to support healthy infant growth. Conclusions This represents a first effort in evaluating Latino mothers’ perceptions of infants’ healthy growth and use growth charts as a potential tool that can help prevent excess weight gain in early infancy.

Pet Ownership and Cancer Risk in the Women's Health Initiative

Abstract: Background: Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. Methods: This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders. Results: There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Conclusion: Pet ownership had no association with overall cancer incidence. Impact: This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311–6. ©2016 AACR . This article is featured in Highlights of This Issue, [p. 1279][1] [1]: /lookup/volpage/25/1279?iss=9

Mediterranean Diet and Breast Cancer

Abstract: Breast cancer remains the most commonly diagnosed cancer in women. Whereas some epidemiological studies generally support the role of diet in breast cancer prevention, conflicting evidence exists, making it challenging to provide a definitive answer on these risks that can be effectively translated to clinical practice and public health recommendations.

Biomarkers of diet and nutritional health

Abstract: Dietary biomarkers are biological specimens that may serve as functional, biochemical, or clinical indicators of nutrient intake or metabolism. The majority of research studies utilize self-report methodologies for the measurement of diet. These include food diaries, repeat 24-h recalls, and food frequency questionnaires. While collecting dietary data by self-report can be cost-effective, it is subject to misreporting. Dietary biomarkers serve as objective measures of nutrient intake and metabolism and markedly increase the validity of diet–disease-related associations, while reducing participant bias due to misreporting. Dietary biomarkers can be classified into one of four groups: recovery, predictive, concentration, and replacement biomarkers. A variety of specimens can be collected for the measurement of dietary biomarkers, including but not limited to sweat, blood, urine, and exhaled gases.This chapter describes various methods for collecting self-reported diet information as well as the different classifications of dietary biomarkers, their relationship to health risk, as well as important considerations when collecting and analyzing biosamples.

Abstract CT043: Low-fat dietary pattern and breast cancer mortality in the Women's Health Initiative (WHI) randomized trial

Abstract: Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Context: The Women's Health Initiative Dietary Modification trial randomized 48,835 postmenopausal women at 40 US clinical centers from 1993 to 1998. With 1,767 incident breast cancers, during 8.3 years (mean) dietary intervention, there were fewer breast cancers in the dietary group (HR 0.92 95% CI 0.84-1.01, P = 0.09) with somewhat fewer deaths from breast cancer (HR 0.77 95% CI 0.48-1.22), but no apparent post-intervention influence (JAMA 2006; 295:629; Cancer Epi Bio Prev 2014; 23:2924). These findings suggested dietary intervention may reduce breast cancers associated with greater mortality. New information on breast cancer mortality is analyzed here. Objective: To examine low-fat dietary pattern influence on breast cancer mortality for cases diagnosed during the dietary intervention period. Design and Setting: Secondary analyses from a randomized controlled dietary modification trial. Participants: 48,835 postmenopausal women, 50 to 79 years old, with no previous breast or colorectal cancer, with dietary fat intake greater than 32% of total energy and with a mammogram not suspicious for cancer at entry. I nterventions: Dietary group (40%, n = 19,541) which included nutritionist led group sessions throughout the 8.3 year (mean) dietary intervention. Usual diet control group participants received diet-related education materials (60%, n = 29,294). Main Outcome Measures: Deaths from breast cancer (breast cancer followed by deaths directly attributed to the cancer) and deaths after breast cancer (breast cancer followed by death from any cause) during 8.3 years (mean) dietary intervention including all 48,835 study participants measured from randomization. Secondarily, breast cancer overall survival (survival from diagnosis with death from any cause) for the 1767 breast cancer cases identified during the dietary intervention period and followed through August, 2014. Results: Baseline demographic characteristics and breast cancer risk factors were closely comparable in the two randomization groups as was screening mammography frequency throughout. In the dietary group, fat intake decreased, vegetable, fruit and grain consumption increased and body weight was modestly reduced (all P <0.001). In the dietary group, deaths from breast cancer were somewhat lower (HR 0.68 95% CI 0.43-1.07, P = 0.09), while deaths after breast cancer were significantly reduced (40 vs 94 cases; HR 0.65 95% CI 0.45-0.94, P = 0.02). Breast cancer overall survival, among the 1,767 breast cancer cases, after 10.9 years (mean) post-diagnosis follow-up, was greater in the dietary group (10 year survival, 82% vs 78%, HR 0.80 95% CI 0.66-0.97, P = 0.02). Temporal trends for dietary modification influence on breast cancer overall survival identified more favorable effect during dietary intervention then post-intervention (interaction P = 0.02). Causes of death (available for 400 of 487 breast cancer cases) included breast cancer (41%, 165 deaths), other cancer (17%, 67 deaths), and cardiovascular disease (16%, 64 deaths, HR 0.45 95% CI 0.25-0.81 for dietary influence). Conclusion: Compared to a usual diet control group, a low-fat dietary pattern led to a lower incidence of deaths after breast cancer. This reduction is due, in part, to better survival following breast cancer diagnosis. Citation Format: Rowan T. Chlebowski, Aaron K. Aragaki, Garnet L. Anderson, Cynthia A. Thomson, Joanne E. Manson, Michael S. Simon, Barbara V. Howard, Thomas E. Rohan, Linda Snetselaar, Dorothy Lane, Wendy E. Barrington, Mara Z. Vitolilns, Catherine Womack, LiHong Qi, Lifang Hou, Fridtjof Thomas, Ross L. Prentice. Low-fat dietary pattern and breast cancer mortality in the Women's Health Initiative (WHI) randomized trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT043.

Job Talks and Interviews: How to Stand Out and Fit In: A Report from the American Society of Preventive Oncology Junior Members Interest Group

Abstract: The mission of the American Society of Preventive Oncology (ASPO) includes fostering the continuing professional development of its members. One major activity of ASPO is to prepare the next generation of cancer prevention and control researchers for successful careers. The process of applying for