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© Oxford University Press 2008.
IN THIS ISSUE
Risk of Death in the US by Age, Sex, and Smoking StatusTo make sense of the important disease risks they face, people need context about how one risk compares with other risks. Unfortunately, messages about health risks often lack such context. To help provide needed perspective, Woloshin et al. (p. 845) used national census and health data for 2004 to create simple one-page charts that present the 10-year chance of dying from various causes according to age, sex, and smoking status. At all ages, the 10-year risk of death from all causes combined is higher for men than women. The effect of smoking on the chance of dying is similar to the effect of adding 5 to 10 years of age. For men who never smoked, heart disease death represents the single largest cause of death from age 50 on. For men who currently smoke, the chance of dying from lung cancer is of the same order of magnitude as the chance of dying from heart disease, and after age 50, it is about 10 times greater than the chance of dying from prostate or colon cancer. For women who never smoked, the 10-year risks of death from breast cancer and heart disease are similar until age 60; thereafter, heart disease represents the single largest cause of death. For women who currently smoke, the chance of dying from heart disease or lung cancer exceeds the chance of dying from breast cancer from age 40 on.
In an editorial, Thun et al. (p. 830) discuss the potential use of these charts in clinical settings to promote behavioral change, such as smoking cessation. They suggest that the numerical risk estimates might have broader use and impact if they could be provided to patients in an interactive format.
Breast Cancer Risk Reduction with Raloxifene
In 2006, after a mean follow-up of 5.6 years, the Raloxifene Use for the Hearth (RUTH) randomized controlled trial found a 44% reduced risk of breast cancer overall among postmenopausal women at increased coronary risk using 60 mg/day raloxifene compared with placebo. Grady et al. (p. 854) now present an analysis of the results of the RUTH trial by tumor type, treatment time, and subgroup. Use of raloxifene was associated with a 55% reduced risk of invasive estrogen receptor–positive breast cancer but with no reduction in invasive estrogen receptor–negative or noninvasive breast cancer. Raloxifene appears to be effective in reducing breast cancer risk regardless of the health characteristics of the women using it or their baseline breast cancer risk.
In an editorial, Jordan (p. 831) reviews the history of laboratory findings that led to the recognition of the importance of selective estrogen receptor modulators and to the development of tamoxifen and raloxifene as drugs to control multiple diseases.
Facility Characteristics and Mammography Performance
The interpretive performance of screening mammography is influenced by characteristics of the women who are being screened and of the interpreting radiologists, but the extent to which it varies by facility-level characteristics is unclear. Taplin et al. (p. 876) conducted a cross-sectional observational study that examined whether mammography facility characteristics reported through a survey accounted for variation in interpretive performance recorded prospectively by mammography facilities. The study included 44 facilities, 484,463 screening mammograms performed on 237,669 women, and 2686 breast cancer diagnoses. Interpretive accuracy of mammography was higher among facilities that offered screening mammograms alone than in those that offered both screening and diagnostic mammograms; that had a breast imaging specialist interpreting mammograms; that did not perform double reading; and that conducted audit reviews two or more times per year. The authors note that understanding how facility characteristics influence performance could allow women and their physicians to choose facilities based on these characteristics and radiology facilities to improve their performance.
Targeting Nuclear Factor-
B to treat melanoma
The transcription factor NF-B plays a regulatory role in cell proliferation, apoptosis, invasion, and metastasis, and its activation may mediate chemoresistance. Schön et al. (p. 862) investigated the antineoplastic properties of KINK-1, a small molecule that specifically inhibits IKKβ, a kinase involved in NF-B activation, in cell lines derived from melanoma. KINK-1 alone had little antiproliferative activity in melanoma cells but increased the activity of cytostatic agents, including camptothecin and doxorubicin, in vitro and prevented doxorubicin-induced NF-B activation. KINK-1 treatment enhanced the therapeutic efficacy of camptothecin and doxorubicin in mice that had been injected with melanoma cells, as reflected in reduced pulmonary metastases and tumor masses.
In an accompanying editorial, Kirkwood et al. (p. 833) describe the biologic basis for targeting NF-B, including the three distinct pathways for NF-B activation. They discuss issues raised by attempting to treat melanoma through NF-B inhibition, including the collateral effects on immune responses that this approach might entail and the possible counter-regulatory response of melanoma cells following IKKβ inhibition.
Trends in the Cost of Initial Cancer Treatment
Little is known about how particular kinds of services contribute to the increased overall costs of cancer treatment. Warren et al. (p. 888) used data from the Surveillance, Epidemiology and End Results–Medicare linked database to assess trends in the costs of cancer-related surgery, chemotherapy, radiation therapy, and other hospitalizations during the period from 2 months prior to diagnosis to 12 months after diagnosis for breast, lung, colorectal, and prostate cancer between 1991 and 2002 as reflected in Medicare reimbursements. The reimbursements for initial care for the four cancers exceeded $6.7 billion in 2002, with costs for hospitalizations accounting for the largest portion of costs. However, given increasing use and costs of chemotherapy and radiation therapy, costs for these treatments may soon equal the costs of hospitalization. The authors suggest that the increase in costs will continue due to demographic factors and rising prices for treatments.
Melatonin and Breast Cancer Risk in Postmenopausal Women
Low urinary melatonin levels have been associated with an increased risk of breast cancer in premenopausal women, but whether this association holds for postmenopausal women has been unclear. Schernhammer et al. (p. 898) investigated this association in a prospective nested case–control study. Increased levels of melatonin's major metabolite, 6-sulfatoxymelatonin, in a baseline 12-hour overnight urine sample were associated with a statistically significantly lower risk of invasive breast cancer. The authors suggest that factors affecting the metabolism of melatonin need to be taken into account in analyses that use this marker.
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