Nicotine dependence, withdrawal symptoms, and adolescents' readiness to quit smoking.

The purpose of this study was to characterize nicotine dependence and nicotine withdrawal symptoms among adolescent smokers and to investigate associations between these key factors and adolescents' readiness to quit smoking. A total of 5624 high school students participated in a school-based survey. Of 1111 adolescents who were current or former smokers, the following stage-of-change distribution for smoking cessation was observed: precontemplation, 52.5%; contemplation, 16.0%; preparation, 7.5%; action, 13.2%; and maintenance, 10.8%. Among current smokers, 18.1% were substantially dependent on nicotine, 45.2% had moderate dependence, and 36.7% had no dependence. Higher proportions of current smokers than successful quitters reported withdrawal symptoms with their most recent quit attempts. Precontemplators exhibited significantly higher mean nicotine dependence scores than did students in the contemplation or preparation stages (F(2,837) = 12.03; p < 0.0001). A similar trend was observed for withdrawal-symptom scores across the stages of change. The nicotine dependence and withdrawal-symptom scores were significantly correlated (r = 0.44, p < 0.001). Nicotine dependence and nicotine withdrawal appear to interfere with adolescents' abilities and readiness to quit smoking, suggesting a potential role for nicotine replacement therapy in the treatment of tobacco use and dependence among adolescents.

Tobacco withdrawal signs and symptoms among women with and without a history of depression.

A past history of depression is associated with a decreased likelihood of quitting smoking. Tobacco withdrawal may be a mechanism through which depression history impedes smoking cessation. This research examined the influence of depression history on unmedicated tobacco withdrawal signs (polysomnographic measures of sleep) and symptoms (self-reported urge, negative affect, hunger, and sleep) among women (N= 13). Depression history was associated with differential withdrawal-induced changes in several REM sleep parameters. Self-report and other polysomnography (sleep fragmentation, slow-wave sleep) measures displayed statistically significant withdrawal effects but did not discriminate between depression history groups. These results suggest that REM sleep parameters may be sensitive to differential tobacco withdrawal responses that are not readily apparent through self-reported symptoms.

Gender differences in response to nicotine replacement therapy: objective and subjective indexes of tobacco withdrawal.

K. A. Perkins (1996) recently proposed that nicotine reinforcement controls smoking to a greater degree among men than women and that consequently, nicotine replacement therapy (NRT) during smoking cessation should benefit men more than women. The authors tested this hypothesis. Polysomnographic measures of sleep and self-report indexes of tobacco withdrawal were collected pre- and postcessation from an active nicotine patch group and a placebo patch group in a randomized, double-blind clinical trial (N = 34). Objective sleep parameters supported Perkins's hypothesis and indicated that among women, NRT may be less effective at suppressing certain withdrawal responses compared with men and may produce some iatrogenic effects. Valid and reliable self-report measures of withdrawal did not reveal gender differences in response to NRT.

Time-dependence of hazard ratios for prognostic factors in primary breast cancer.

Some prognostic factors, such as steroid receptors, appear strongly related to outcome in early studies with short follow-up, but as follow-up matures the relationships appear to weaken. We investigated this phenomenon for several factors (tumor size, axillary lymph nodes, S-phase fraction, estrogen receptor (ER) status, and adjuvant therapy) in a large sample of breast cancer cases (N=2,873) with up to 17 years of follow-up for disease-free survival (DFS). Subjects in the study were identified from patients who had hormone receptor assays performed in our laboratory. Analysis of DFS included fitting a multivariate Cox proportional hazards model, testing for nonproportionality, and examining diagnostic plots. The assumption of proportional hazards was violated for several factors including ER, tumor size, and S-phase fraction. For ER, the hazard ratio was initially less than 1.0, indicating a good effect on prognosis, but increased at later times to values greater than 1.0, indicating a bad effect on prognosis. In contrast, the hazard ratios for tumor size and S-phase were initially high and decreased asymptotically toward 1.0 over time. Analysis of p53 expression in a subset of cases yielded qualitatively similar results. We conclude that several standard prognostic factors (ER, tumor size, S-phase fraction) and possibly other investigational factors have important but nonproportional effects on hazard. It is likely that violation of proportional hazards is common and not limited to breast cancer. Failure to recognize violations of proportional hazards can lead to both over- and under-estimation of the effects of important prognostic factors.

Lack of prognostic value of cathepsin D levels for predicting short term outcomes of breast cancer patients.

The value of cathepsin D determinations done on tumor cytosols in evaluating the prognosis of breast cancer patients has been debated in the literature. Our previous work suggested that cathepsin D determinations were not of prognostic value, but in that study we used immunoblotting and immunohistochemical methods rather than the more widely used double antibody immunoradiometric (IRMA) assay for measuring cathepsin levels. Here we report our results determining cathepsin D using components of a commercially available IRMA system on a large patient sample (n = 1984). Reagents from a commercially available IRMA kit were used to analyze cathepsin D levels in the cytosols of 1984 patients with breast cancer. All patients had invasive breast cancer with known tumor size and with some axillary nodes pathologically examined. Only patients with T1 and T2 tumor sizes were included. Median follow-up was 37 months. The hypothesis that high cathepsin D levels correlated with poorer outcome (poorer DFS or OS) was not confirmed, either in all patients, or in node-positive or node-negative subsets. Only in patients treated with adjuvant therapy were higher cathepsin D levels correlated with negative outcome (worsened OS, but not DFS), although given the large number of subsets analyzed this correlation may be spurious. Multivariate analyses using interaction terms did not support the concept that high cathepsin D levels correlate with resistance to adjuvant therapy. In this study evaluating the value of cathepsin D using components from a kit widely used for measuring cathepsin D levels, we conclude that cathepsin D is of doubtful value in predicting risk of early relapse or death for patients with newly diagnosed invasive breast cancer.