Light smoking at base-line predicts a higher mortality risk to women than to men; evidence from a cohort with long follow-up

BACKGROUND: There is conflicting evidence as to whether smoking is more harmful to women than to men. The UK Cotton Workers’ Cohort was recruited in the 1960s and contained a high proportion of men and women smokers who were well matched in terms of age, job and length of time in job. The cohort has been followed up for 42 years. METHODS: Mortality in the cohort was analysed using an individual relative survival method and Cox regression. Whether smoking, ascertained at baseline in the 1960s, was more hazardous to women than to men was examined by estimating the relative risk ratio women to men, smokers to never smoked, for light (1–14), medium (15–24), heavy (25+ cigarettes per day) and former smoking. RESULTS: For all-cause mortality relative risk ratios were 1.35 for light smoking at baseline (95% CI 1.07-1.70), 1.15 for medium smoking (95% CI 0.89-1.49) and 1.00 for heavy smoking (95% CI 0.63-1.61). Relative risk ratios for light smoking at baseline for circulatory system disease was 1.42 (95% CI 1.01 to 1.98) and for respiratory disease was 1.89 (95% CI 0.99 to 3.63). Heights of participants provided no explanation for the gender difference. CONCLUSIONS: Light smoking at baseline was shown to be significantly more hazardous to women than to men but the effect decreased as consumption increased indicating a dose response relationship. Heavy smoking was equally hazardous to both genders. This result may help explain the conflicting evidence seen elsewhere. However gender differences in smoking cessation may provide an alternative explanation

Adjuvant radiotherapy and chemotherapy in breast cancer: 30 year follow-up of survival

BACKGROUND:The long term outcome (more than 15 years) of adjuvant treatment in patients with primary operable breast cancer has rarely been examined.METHODS:A randomised clinical trial of radiotherapy, chemotherapy (28 day cycles of cyclophosphamide, methotrexate and 5-fluorouracil) or both on women with primary operable breast cancer (n = 322) was followed-up for a median of 27 years.RESULTS:260 (81%) patients died, 204 (78%) from breast cancer. Cancer specific survival (SE) at 10 years, 20 years and 30 years was 41 (3)%, 34 (3)% and 33 (3)% respectively. Presence of more than 3 involved lymph nodes increased cancer-specific mortality (HR 1.88, 95% CI 1.34-2.63) after adjustment for age, socio-economic deprivation and adjuvant treatment. Both age (HR 1.63, 95% CI 1.19-2.22) and involved lymph nodes (HR 1.59, 95% CI 1.17-2.14) were significant predictors of all-cause mortality after adjustment for other factors. There was no significant difference in all-cause or cancer-specific survival between patients in each of the 3 treatment arms.CONCLUSIONS:The present study highlights the long term impact of node positive disease but does not indicate that any regimen was associated with significantly better long-term surviva

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Estrogen receptor degradation: a CUE for endocrine resistance?

Despite the undoubted success of adjuvant endocrine therapies that target the estrogen receptor pathway, not all women with estrogen receptor-positive breast cancer respond to these therapies, and many who initially respond will subsequently relapse. Deregulation of various aspects of estrogen receptor signaling has been highlighted as a mechanism of resistance and as a basis for alternative therapeutic approaches. However, a recent publication refocuses attention on the estrogen receptor itself by showing that the ubiquitin-binding CUE domain-containing protein 2 is a regulator of estrogen receptor protein degradation and a marker of endocrine resistance in breast cancer

Competing risk and heterogeneity of treatment effect in clinical trials

It has been demonstrated that patients enrolled in clinical trials frequently have a large degree of variation in their baseline risk for the outcome of interest. Thus, some have suggested that clinical trial results should routinely be stratified by outcome risk using risk models, since the summary results may otherwise be misleading. However, variation in competing risk is another dimension of risk heterogeneity that may also underlie treatment effect heterogeneity. Understanding the effects of competing risk heterogeneity may be especially important for pragmatic comparative effectiveness trials, which seek to include traditionally excluded patients, such as the elderly or complex patients with multiple comorbidities. Indeed, the observed effect of an intervention is dependent on the ratio of outcome risk to competing risk, and these risks – which may or may not be correlated – may vary considerably in patients enrolled in a trial. Further, the effects of competing risk on treatment effect heterogeneity can be amplified by even a small degree of treatment related harm. Stratification of trial results along both the competing and the outcome risk dimensions may be necessary if pragmatic comparative effectiveness trials are to provide the clinically useful information their advocates intend

Meta-analysis of trials comparing anastrozole and tamoxifen for adjuvant treatment of postmenopausal women with early breast cancer

<p>Abstract</p> <p>Objective</p> <p>It was aimed to review the literature and make a meta-analysis of the trials on both upfront, switching, and sequencing anastrozole in the adjuvant treatment of early breast cancer.</p> <p>Methods</p> <p>The PubMed, ClinicalTrials.gov and Cochrane databases were systematically reviewed for randomized-controlled trials comparing anastrozole with tamoxifen in the adjuvant treatment of early breast cancer.</p> <p>Results</p> <p>The combined hazard rate of 4 trials for event-free survival (EFS) was 0.77 (95%CI: 0.70–0.85) (<it>P </it>< 0.0001) for patients treated with anastrozole compared with tamoxifen. In the second analysis in which only ITA, ABCSG 8, and ARNO 95 trials were included and ATAC (upfront trial) was excluded, combined hazard rate for EFS was 0.64 (95%CI: 0.52–0.79) (<it>P </it>< 0.0001). In the third analysis including hazard rate for recurrence-free survival (excluding non-disease related deaths) of estrogen receptor-positive patients for ATAC trial and hazard rate for EFS of all patients for the rest of the trials, combined hazard rate was 0.73 (95%CI: 0.65–0.81) (<it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>Anastrozole appears to have superior efficacy than tamoxifen in the adjuvant hormonal treatment of early breast cancer. Until further clinical evidence comes up, aromatase inhibitors should be the initial hormonal therapy in postmenopausal early breast cancer patients and switching should only be considered for patients who are currently receiving tamoxifen.</p

Exercise and postprandial lipemia: effects on vascular health in inactive adults

Background: There is evidence to suggest that postprandial lipemia are is linked to the impairment of endothelial function, which is characterized by an imbalance between the actions of vasodilators and vasoconstrictors. The aim of this study was to determine the effects of a 12-week high-intensity training (HIT) and moderate continuous training (MCT) protocol on postprandial lipemia, vascular function and arterial stiffness in inactive adults after high-fat meal (HFM) ingestion. Methods: A randomized clinical trial was conducted in 20 healthy, inactive adults (31.6 ± 7.1 years). Participants followed the two exercise protocols for 12 weeks. To induce a state of postprandial lipemia (PPL), all subjects received a HFM. Endothelial function was measured using flow-mediated vasodilation (FMD), normalized brachial artery FMD (nFMD), aortic pulse wave velocity (PWV) and augmentation index (AIx). Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides and glucose were also measured. Results: The effects of a HFM were evaluated in a fasted state and 60, 120, 180, and 240 min postprandially. A significant decrease in serum glucose between 0 min (fasted state) and 120 min postprandially was found in the HIT group (P= 0. 035). Likewise, FMD (%) was significantly different between the fasted state and 60 min after a HFM in the HIT group (P = 0.042). The total cholesterol response expressed as area under curve (AUC)(0–240) was lower following HIT than following MCT, but no significant differences were observed (8%, P > 0.05). Similarly, triglycerides AUC(0–240) was also lower after HIT compared with MCT, which trended towards significance (24%, P= 0.076). The AUC(0–240) for the glucose response was significantly lower following HIT than MCT (10%, P = 0.008). FMD and nFMD AUC(0–240) were significantly higher following HIT than following MCT (46.9%, P = 0.021 and 67.3%, P = 0.009, respectively). PWV AUC(0–240) did not differ following between the two exercise groups (2.3%, P > 0.05). Conclusions: Supervised exercise training mitigates endothelial dysfunction and glucose response induced by PPL. Exercise intensity plays an important role in these protective effects, and medium-term HIT may be more effective than MCT in reducing postprandial glucose levels and attenuating vascular impairment.This study as funded in part by the Center for Studies on Measurement of Physical Activity, School of Medicine and Health Sciences, Universidad del Rosario (Code N° FIUR DN-BG001). We declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or appropriate data manipulatio