Trends of Incidence and Survival of Gastrointestinal Neuroendocrine Tumors in the United States: A Seer Analysis

OBJECTIVES: To examine trends in detection and survival of hollow viscus gastrointestinal neuroendocrine tumors (NETs) across time and geographic regions of the U.S

Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies

Hypothesized role of pregnancy hormones on HER2+breast tumor development

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies >/=1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of 45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors

Associations between ACE-Inhibitors, Angiotensin Receptor Blockers, and Lean Body Mass in Community Dwelling Older Women

Studies suggest that ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM) among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women’s Health Initiative participants that received dual energy X-ray absorptiometry scans to estimate body composition (n=10,635) at baseline and at years 3 and 6 of follow-up. Of those, 2642 were treated for hypertension at baseline. Multivariate linear regression models, adjusted for relevant demographics, behaviors, and medications, assessed ACE-I/ARB use/nonuse and LBM associations at baseline, as well as change in LBM over 3 and 6 years. Although BMI did not differ by ACE-I/ARB use, LBM (%) was significantly higher in ACE-I/ARB users versus nonusers at baseline (52.2% versus 51.3%, resp., p=0.001). There was no association between ACE-I/ARB usage and change in LBM over time. Reasons for higher LBM with ACE-I/ARB use cross sectionally, but not longitundinally, are unclear and may reflect a threshold effect of these medications on LBM that is attenuated over time. Nevertheless, ACE-I/ARB use does not appear to negatively impact LBM in the long term

Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development

It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3-year intervention in a subset of participants randomized to oral UDCA at 8-10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA-associated shift in microbial community composition (P 0.05). These UDCA-associated shifts in microbial community distance metrics from baseline to end-of-study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post-UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow-up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex-specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk.Partnership for Native American Cancer Prevention [NIH/NCI U54CA143924, U54CA143925]; NSF [1565100]; Biostatistics and Tissue Acquisition and Cellular/Molecular Analysis Shared Resources - NCI [P30CA023074]; [R01 CA151708]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Quit Outcomes and Program Utilization by Mode of Entry Among Clients Enrolling in a Quitline

Purpose: To investigate how mode of entry into a quitline influences program utilization and quit outcomes among clients seeking cessation services. Design: This is a retrospective analysis of clients receiving quitline services from January 2011 to June 2016. Setting: The study was conducted at the Arizona Smokers' Helpline. Participants: Enrolled clients completed a 7-month follow-up (N = 18 650). Measures: The independent variable was referral mode of entry (ie, proactive, passive, and self-referral). Outcome variables included tobacco cessation medication use, number of coaching sessions completed, and 30-day tobacco abstinence at 7 months. Analysis: Logistic regression was used to analyze tobacco abstinence after controlling for potential confounders. Results: Compared to self-referred clients, proactively referred clients were least likely (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.81-0.97), whereas passively referred clients were most likely (OR: 1.14; 95% CI: 1.00-1.30) to report tobacco abstinence. Proactively referred (OR: 0.79; 95% CI: 0.70-0.88), but not passively referred, clients were 21% less likely to report tobacco cessation medication use than self-referred clients. Conclusion: Proactive referrals are associated with lower utilization of tobacco cessation medication and less successful quit outcomes; however, provider referrals are critical to reaching tobacco users who may have more significant health risks and barriers to quitting. Examining potential barriers among both providers and provider-referred clients is needed to inform improvements in training providers on brief interventions for tobacco cessation.Arizona Department of Health Services [ADHS11-007339, ADHS16-106672, ADHS13-026130:5]; National Cancer Institute [P30 CA023074]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Gender differences in utilization of services and tobacco cessation outcomes at a state quitline

Research suggests that women may have poorer tobacco cessation outcomes than men; however, the literature is somewhat mixed. Less is known about gender differences in cessation within quitline settings. This study examined gender differences in the utilization of services (i.e., coaching sessions, pharmacotherapy) and tobacco cessation among callers to the Arizona Smokers’ Helpline (ASHLine). The study sample included callers enrolled in ASHLine between January 2011 and June 2016. We tracked number of completed coaching sessions. At the 7-month follow-up, callers retrospectively reported use of cessation pharmacotherapy (gum, patch, or lozenge), as well as current tobacco use. Associations between gender and tobacco cessation were tested using logistic regression models. At month 7, 36.4% of women (3,277/9,004) and 40.3% of men (2,960/7,341) self-reported 30-day point prevalence abstinence. Compared to men, fewer women reported using pharmacotherapy (women: 71.4% vs. men: 73.6%, p = .01) and completed at least five coaching sessions (women: 35.1% vs. men: 38.5%, p < .01). After adjusting for baseline characteristics, women had significantly lower odds of reporting tobacco cessation than men (OR = 0.91, 95% CI: 0.84 to 0.99). However, after further adjustment for use of pharmacotherapy and coaching, there was no longer a significant relationship between gender and tobacco cessation (OR: 0.96, 95% CI: 0.87 to 1.06). Fewer women than men reported tobacco cessation. Women also had lower utilization of quitline cessation services. Although the magnitude of these differences were small, future research on improving the utilization of quitline services among women may be worth pursuing given the large-scale effects of tobacco.Arizona Department of Health Services [ADHS13-026130, ADHS11-007339, HS160051-0/E1H37741]; National Cancer Institute of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA023074]12 month embargo; published online: 07 August 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Optimism and Diet Quality in the Women\u27s Health Initiative

Diet quality has not been well studied in relation to positive psychological traits. Our purpose was to investigate the relationship between optimism and diet quality in postmenopausal women enrolled in the Women\u27s Health Initiative observational study (OS) and clinical trials (CTs), and to determine whether optimism was associated with diet change after a 1-year dietary intervention. Diet quality was scored with the Alternate Healthy Eating Index (AHEI) and optimism assessed with the Life Orientation Test-Revised. Baseline characteristics were compared across AHEI quintiles or optimism tertiles using regression models with each variable of interest as a function of quintiles or tertiles (OS, n=87,630; CT, n=65,360). Association between optimism and baseline AHEI and change in AHEI over 1 year were tested using multivariate linear regression (CT, n=13,645). Potential interaction between optimism and trial arm and demographic/lifestyle factors on AHEI change was tested using likelihood ratio test (CT intervention, n=13,645; CT control, n=20,242). Women reporting high AHEI were non-Hispanic white, educated, physically active, past or never smokers, hormone therapy users, had lower body mass index and waist circumference, and were less likely to have chronic conditions. In the CT intervention, higher optimism was associated with higher AHEI at baseline and with greater change over 1 year (P=0.001). Effect modification by intervention status was observed (P=0.014), whereas control participants with highest optimism achieved threefold greater AHEI increase compared with those with the lowest optimism. These data support a relationship between optimism and dietary quality score in postmenopausal women at baseline and over 1 year

Levels of rectal mucosal polyamines and prostaglandin E2 predict ability of DFMO and sulindac to prevent colorectal adenoma.

Background &amp; aimsCombination of polyamine and prostaglandin E2 (PGE2)-synthesis inhibitors reduced the risk of colorectal adenoma (CRA) by 70% in patients who received polypectomies. We studied effects of the combination of difluoromethylornithine (DFMO) and sulindac on biomarkers and investigated factors that modify their efficacy.MethodsWe analyzed rectal mucosal levels of polyamines (spermidine, spermine, and putrescine) and PGE2, treatment regimens, and risk of CRA in 267 participants of a phase IIb/III chemoprevention trial of DFMO/sulindac.ResultsIn the group that received DFMO/sulindac, spermidine-to-spermine ratio (Spd:Spm) in rectal mucosa decreased between baseline and 12- and 36-month follow-up examinations (0.30, 0.23, and 0.24, respectively; P &lt; .001 for both comparisons to baseline). Putrescine levels decreased between baseline and 12 months (0.46 vs 0.15 nmol/mg protein; P &lt; .001) but rebounded between 12 and 36 months (0.15 vs 0.36 nmol/mg protein; P = .001). PGE2 levels did not change, although aspirin use was significantly associated with lower baseline levels of PGE2. No significant associations were observed between changes in biomarker levels and efficacy. However, drug efficacy was greatest in subjects with low Spd:Spm and high PGE2 at baseline; none of these subjects, versus 39% of those given placebo, developed CRA (P &lt; .001). Efficacy was lowest in subjects with high Spd:Spm and low PGE2 at baseline; 28% developed CRA, compared with 36% of patients given placebo (P = .563).ConclusionsA combination of DFMO and sulindac significantly suppressed production of rectal mucosal polyamines but not PGE2. No relationship was found between changes in biomarker levels and response. However, baseline biomarker levels modified the effect of DFMO/sulindac for CRA prevention