Obese men are at an increased risk of chronic disease and are far less likely than women to attempt weight loss. There is a need to successfully recruit men to weight loss clinical trials. Overweight and obese men were recruited to a 6-month, randomized, controlled weight loss trial. Initial recruitment efforts were aimed at men in the workplace with less than or equal to 2 years of college education. After unsatisfactory interest from men and businesses alike, recruitment strategy shifted to enroll men outside the workplace with any educational background. Recruitment methods included word of mouth, email and website advertisements, printed posters in local businesses and doctors’ offices, Facebook ads, and a 1-week newspaper ad campaign. Initial interest and enrollment was negligible with only 35 men enrolled in the first 7 months. The launch of a 1-week newspaper advertisement was the most useful recruitment technique and 102 overweight/obese men were successfully enrolled. Study retention remained high throughout the Gutbusters program, indicating targeted, effective recruitment, and not weight loss interest, may be the largest barrier to trial participation for overweight and obese men.

Overweight and obese men were recruited to a 6-month, randomized controlled weight loss trial, which compared the Gutbusters weight loss program alone to the Gutbusters program with incentives for successful weight loss. The intervention was delivered primarily online, with weekly in-person weight collections. Gutbusters was designed using a template from the REFIT intervention and encouraged participants ( N = 102, 47.0 ± 12.3 years, 32.5 kg/m2) to make six 100-calorie changes to their typical daily diet for a total of 42 changes per week. Weight loss was significantly greater in the Gutbusters+Incentive group compared to the Gutbusters alone group at both 12 and 24 weeks ( p’s = < .01). The Gutbusters+Incentive group’s a mean weight loss was 9.9 pounds at 12 weeks (95% CI: 6.9, 12.9) and 8.4 pounds at 24 weeks (95% CI: 3.9, 13.0). The Gutbusters alone group mean weight loss was 3.7 pounds at 12 weeks (95% CI: –.06, 7.5) and 3.4 pounds at 24 weeks (95% CI: –2.2, 9.0). This study adds to the literature of behavioral weight programs that are designed for men. Unlike the majority of previous male weight loss interventions, which were designed with an intervention comparison to a no treatment or waitlist control, Gutbusters was implemented as a comparative effectiveness trial, which will help bolster the evidence base for real-world application.

Statins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women. Premenopausal women at increased risk for breast cancer received either 40 mg of atorvastatin or placebo for 1 year. Biomarker assessment was performed prior to initiation and at completion of study medication. MD was determined using both Breast Imaging Reporting and Data System and the visual analogue scale. Serum IGF-1 was determined by ELISA assay at the end of the study. Sixty-three women were enrolled between December 2005 and May 2010. Sixteen (25%) women withdrew. The mean age of participants was 43 (range, 35–50), 100% were white, and the average body mass index (BMI) was 26.4. The statin group demonstrated a significant decrease in cholesterol and low-density lipoprotein (LDL), suggesting compliance with study medication. After accounting for BMI, there was no difference in change in MD between groups. There was a significant increase in serum IGF-1 in the statin group. In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer, we did not see an effect of atorvastatin on MD. Further investigation of statins may be warranted; however, design of prior trials and potential mechanism of action of the agent need to be considered in the design of future trials.

BackgroundA germline, variant in the BRCA1 3’UTR (rs8176318) was previously shown to predict breast and ovarian cancer risk in women from high-risk families, as well as increased risk of triple negative breast cancer. Here, we tested the hypothesis that this variant predicts tumor biology, like other 3’UTR mutations in cancer.MethodsThe impact of the BRCA1-3’UTR-variant on BRCA1 gene expression, and altered response to external stimuli was tested in vitro using a luciferase reporter assay. Gene expression was further tested in vivo by immunoflourescence staining on breast tumor tissue, comparing triple negative patient samples with the variant (TG or TT) or non-variant (GG) BRCA1 3’UTR. To determine the significance of the variant on clinically relevant endpoints, a comprehensive collection of West-Irish breast cancer patients were tested for the variant. Finally, an association of the variant with breast screening clinical phenotypes was evaluated using a cohort of women from the High Risk Breast Program at the University of Vermont.ResultsLuciferase reporters with the BRCA1-3’UTR-variant (T allele) displayed significantly lower gene expression, as well as altered response to external hormonal stimuli, compared to the non-variant 3’UTR (G allele) in breast cancer cell lines. This was confirmed clinically by the finding of reduced BRCA1 gene expression in triple negative samples from patients carrying the homozygous TT variant, compared to non-variant patients. The BRCA1-3’UTR-variant (TG or TT) also associated with a modest increased risk for developing breast cancer in the West-Irish cohort (OR = 1.4, 95% CI 1.1-1.8, p = 0.033). More importantly, patients with the BRCA1-3’UTR-variant had a 4-fold increased risk of presenting with Stage IV disease (p = 0.018, OR = 3.37, 95% CI 1.3-11.0). Supporting that this finding is due to tumor biology, and not difficulty screening, obese women with the BRCA1-3’UTR-variant had significantly less dense breasts (p = 0.0398) in the Vermont cohort.ConclusionA variant in the 3’UTR of BRCA1 is functional, leading to decreased BRCA1 expression, modest increased breast cancer risk, and most importantly, presentation with stage IV breast cancer, likely due to aggressive tumor biology.

PurposeBreast MRI added to mammography increases screening sensitivity for high-risk women but false-positive (FP) rates are higher and the optimal screening schedule for coordination with mammography is unclear. We compare rates of FP MRI when studies were performed on two different schedules.Patients and methodsHigh-risk women at the University of Vermont who had at least 1 MRI and 1 mammogram performed within one year between 2004–2012 were eligible for inclusion in this study. Screening was considered stacked if both studies were performed within 90 days and alternating if studies were 4–8 months apart. False positive was defined in one of three ways.Results137 women had screening which met inclusion criteria and 371 MRIs were reviewed. The FP rates were similar for the two schedules when considering BI-RAD 4, 5, 0 or biopsy as a positive test. FP rates were significantly higher for the stacked schedule (18.2 vs. 10.2%, p = 0.026) when considering BI-RADS 3-4-5-0 as positive test, due to the elevated rate of BI-RADS 3 assessments among stacked exams.ConclusionFalse positive rates differ based on the type of exam (baseline or subsequent) and definition of positive but do not differ based on imaging schedule (stacked or alternating); suggesting that women and their providers may choose the imaging schedule they prefer. This is significant as a randomized clinical trial comparing the two schedules is not likely to be performed, given the high cost and large number of women needed for such a study.