Integration of Universal Germline Genetic Testing for All New Breast Cancer Patients.

BACKGROUND: The American Society of Breast Surgeons recommends genetic testing (GT) for all women with breast cancer (BC), but implementation and uptake of GT has not been well-described. METHODS: A retrospective chart review was performed for newly diagnosed BC patients or patients with a newly identified recurrence of BC seen in a multidisciplinary clinic (MDBC) who were offered genetic counseling (GC) and GT. RESULTS: The 138 women attending the MDBC had a median age of 54 years and comprised non-Hispanic whites (46%), Asians (28%), Hispanics (17%), blacks (4%), and other (5%). Of the 105 (76%) patients without prior GT, 100 (95%) accepted GC, with 93 (93%) of these 100 patients undergoing GT. The patients meeting the National Comprehensive Cancer Network (NCCN) guidelines for GT were more likely to undergo GT. Testing was performed with a 67- to 84-gene panel, together with an 8- to 9-gene STAT panel if needed. Among 120 patients with reports available, including 33 patients previously tested, 15 (12%) were positive (1 BLM, 1 BRCA1, 3 BRCA2, 1 BRIP1, 1 CFTR, 1 CHEK2, 1 MUTYH, 1 PALB2, 1 PRSS1, 1 RAD50, 1 RET, and 2 TP53), 44 (37%) were negative, and 61 (51%) had an uncertain variant. The median time to STAT results (n = 50) was 8 days. The STAT results were available before surgery for 47 (98%) of the 48 STAT patients undergoing surgery. CONCLUSIONS: New BC patients attending the MDBC demonstrated high rates of acceptance of GC and GT. The combination of GC and GT can offer timely information critical to patient risk assessment and treatment planning.

Evidence for racial/ethnic disparities in emergency department visits following breast cancer surgery among women in California: a population-based study.

PURPOSE: Racial/ethnic disparities in breast cancer outcomes may be related to quality of care and reflected in emergency department (ED) visits following primary treatment. We examined racial/ethnic variation in ED visits following breast cancer surgery. METHODS: Using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development, we identified 151,229 women diagnosed with stage 0-III breast cancer between 2005 and 2013 who received surgical treatment. Differences in odds of having at least one breast cancer-related ED visit within 90 days post-surgery were estimated with logistic regression controlling for clinical and sociodemographic variables. Secondary analyses examined health care-related moderators of disparities. RESULTS: Hispanics and non-Hispanic (NH) Blacks had an increased likelihood of having an ED visit within 90 days of surgery compared to NH Whites [OR = 1.11 (1.04-1.18), p = 0.0016; OR = 1.38 (1.27-1.50), p < 0.0001, respectively]; the likelihood was reduced in Asian/Pacific Islanders [aOR = 0.77 (0.71-0.84), p < 0.0001]. Medicaid and Medicare (vs. commercial insurance) increased the likelihood of ED visit for NH Whites, and to a lesser degree for Hispanics and NH Blacks (p < 0.0001 for interaction). Receipt of surgery at an NCI-designated Comprehensive Cancer Center or at a for-profit (vs. non-profit) hospital was associated with reduced likelihood of ED visits for all groups. CONCLUSION: Racial/ethnic disparities in ED visits following breast cancer surgery persist after controlling for clinical and sociodemographic variables. Improving quality of care following breast cancer surgery could improve outcomes for all groups.

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

BACKGROUND AND OBJECTIVE: Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. METHODS: Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. RESULTS: Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296).

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

UNLABELLED: The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (α4ß2* subtype) availability using PET imaging of the radiotracer 2-(18)F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-(18)F-FA-85380, or 2-(18)F-FA). METHODS: Twenty-four smokers-12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR ≥ 0.26)-underwent 2-(18)F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans. RESULTS: Thalamic nAChR α4ß2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability. CONCLUSION: The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine.

An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.

RATIONALE: Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. OBJECTIVES: This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. RESULTS: This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). CONCLUSIONS: A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.

Evidence for endogenous formation of N'-nitrosonornicotine in some long-term nicotine patch users.

INTRODUCTION: Nitrosation of nicotine or its metabolites in the human body could lead to formation of the 2 carcinogenic tobacco-specific nitrosamines-N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). METHODS: We investigated the possibility of endogenous formation of NNN in people who had stopped smoking and used the 21-mg nicotine patch for 6 months. We quantified urinary biomarkers of exposure to NNN-the sum of NNN and its pyridine-N-glucuronide, referred to as total NNN. Also measured were NNK metabolites-the sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides, referred to as total NNAL. RESULTS: The average decline of urinary total NNN was less drastic than that of total NNAL: 22% of baseline total NNN and 7.3% of baseline total NNAL were detected in urine 24 weeks after smoking cessation and patch use (p = .02). The average ratio of total NNN to total NNAL in the same urine samples increased from 0.14 in baseline urine to 0.38 after 24 weeks of nicotine patch use. DISCUSSION: Overall, these results demonstrate that endogenous formation of NNN may occur in nicotine patch users. However, the levels of urinary total NNN during patch use were generally extremely low. Moreover, in 10 of 20 subjects analyzed here, the rate of decline in total NNN was similar to that in total NNAL, indicating that endogenous formation of NNN is virtually nonexistent in these subjects. Supplementation with ascorbic acid could be a simple approach to block possible NNN formation in nicotine patch users.

Comparing cancer patients who enroll in a smoking cessation program at a comprehensive cancer center with those who decline enrollment.

BACKGROUND: Despite the availability of smoking interventions for cancer patients, many eligible patients decline enrollment into such programs. We examined reasons patients provide for declining smoking treatment and compared treatment decliners to enrollees. METHODS: Eligible cancer patients (N = 231) were offered smoking cessation treatment. During recruitment, demographic, medical (eg, cancer stage), and smoking-related behavioral (eg, readiness to quit) data were collected, and decliners stated a reason for refusal. Patients who enrolled in the cessation program (N = 109) were compared with those who declined (N = 122) in terms of recruitment data, and reasons for declining were compiled. RESULTS: Decliners were significantly more likely to: (1) have head and neck cancer (vs lung cancer); (2) exhibit fewer physical symptoms (eg, shortness of breath); (3) report a lower readiness to quit smoking; (4) indicate no intention to quit smoking; and (5) smoke fewer cigarettes. A preference to quit without professional assistance was the most common reason for declining treatment. CONCLUSIONS: Our findings highlight important differences between patients who enroll in a smoking cessation program and those who decline and underscore the need for motivational interventions to facilitate enrollment into smoking interventions for cancer patients.

Influence of methylphenidate on eating in obese men.

OBJECTIVE: Rapid synaptic dopamine transport or reduced brain dopamine receptor signaling may influence energy intake. Methylphenidate, a dopamine reuptake inhibitor, increases brain synaptic dopamine and produces anorexia, suggesting that it may reduce energy intake. We investigated the effects of two doses of short-acting methylphenidate on energy intake over one meal in obese adult males. RESEARCH METHODS AND PROCEDURES: Nine obese males (>85th BMI percentile) ingested a placebo or a moderate dose (0.5 mg/kg) or a high dose (1.0 mg/kg) of methylphenidate in a within-subject double-blind acute laboratory study. One hour after ingestion, pizza consumption was measured in a naturalistic laboratory setting. RESULTS: Participants reduced energy intake by 23% for the moderate dose vs. the placebo (p < 0.02), but there was no significant difference for the high dose vs. the moderate dose (p > 0.05). Participants consumed 34% fewer kilocalories after ingesting the lowest effective dose of methylphenidate compared with placebo (725.7 +/- 404.5 vs.1095 +/- 271.1 kcal, p < 0.01). Seven of nine subjects responded to the moderate dose. The increase in perceived drug effect above placebo was correlated with the reduction in energy intake for both the moderate (r = -0.85, p = 0.004) and the high (r = -0.75 p = 0.021) doses. Hunger scores were not different across drug doses or placebo before drug administration. DISCUSSION: Methylphenidate reduced energy intake of a highly palatable food over one meal by one-third in obese adult males. Dopamine transport inhibition may be an effective component of a comprehensive treatment for obesity.