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© Oxford University Press 2008.
IN THIS ISSUE
Nationwide Audit of Cervical Cancer Screening in SwedenThe effectiveness of cervical cancer screening programs differs widely in different populations. To better understand why cervical cancers occur despite organized screening, Andrae et al. (p. 622) conducted a comprehensive nationwide audit of the effectiveness of the organized cervical cancer screening program in Sweden. Not having had a Pap smear taken within the recommended screening interval was the most important risk factor for cervical cancer in the presence of a screening program. The screening program was equally effective for women of all ages, including women younger than 30, and was also effective against nonsquamous cancers. The authors conclude that compliance with screening recommendations and high population coverage of screening are vital to the success of organized screening programs.
In an editorial, Cuzick (p. 605) describes three broad groups of screening failures and discusses the remedial action that is needed for each. He notes that routine audits within screening programs are needed if screening is to achieve its full potential.
Cost of Care for Elderly Cancer Patients in the United States
Timely estimates of the costs of care for cancer patients are an important element in the formulation of national cancer programs and policies. Yabroff et al. (p. 630) estimated net costs of care for elderly cancer patients in the United States for the 18 most prevalent cancers and for all other tumor sites combined by use of SEER–Medicare claims files. Costs of care were estimated for each phase of care (initial, continuing, and last year of life), applied to survival data to estimate 5-year costs of care, and then extrapolated to newly diagnosed cancer patients. Across tumor sites, mean net costs of care were highest during the initial phase of care and last year of life and lowest in the continuing phase. Five-year costs to Medicare were highest for lung, colorectal, and prostate cancers. The authors conclude that costs of cancer care to Medicare are substantial and vary by tumor site, phase of care, stage at diagnosis, and survival.
In an editorial, Lipscomb (p. 607) discusses the need for empirically strong estimates of cancer care costs and proposes ways to make cancer cost estimates even more useful. He also notes that, for both the elderly and non elderly, additional focus is required on the indirect costs of cancer, reflecting losses in productivity and earnings attributable to cancer-related mortality and morbidity.
Bortezomib Sensitization of Solid Tumors to TRAIL-Mediated Death
Bortezomib is a proteasome inhibitor that has been FDA approved for the treatment of multiple myeloma. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has antitumor activity in mouse models. Shanker et al. (p. 649) examined renal and breast cancer cell lines for changes in mitochondrial depolarization and caspase activity after treatment with TRAIL alone and in combination with bortezomib. The authors also used these cell lines in mouse models of renal and breast cancer to compare tumor metastasis and survival after treatment with bortezomib, the TRAIL receptor agonist antibody MD5-1, and the combination. Bortezomib sensitized tumor cells to TRAIL-mediated apoptosis mainly through the extrinsic cell death pathway. Mice treated with bortezomib and MD5-1 formed fewer lung metastases and lived longer than mice treated with either single agent. The authors conclude that the combination may be useful in the treatment of solid metastatic tumors.
Pesticides and Risk of Testicular Germ Cell Tumors
Persistent organochlorine pesticides may increase the risk of testicular germ cell tumors (TGCTs), possibly by disrupting endocrine signaling. McGlynn et al. (p. 663) analyzed associations between serum levels of 11 of these chemicals and risk of TGCTs in a population of US servicemen. Comparing levels in men who had developed a TGCT by age 45 and in matched control subjects, they found associations between plasma levels of p,p'–dichlorodiphenyltrichloroethylene and two components of chlordane, cis-nonachlor and trans-nonachlor, and risk of TGCTs. The authors suggest that with more widespread use of persistent organochlorine pesticides being discussed, studies of the association of persistent organochlorine pesticides and TGCTs in other populations should be considered.
CYP2D6 Variation and Endocrine Therapy for Breast Cancer
In two clinical trials of postmenopausal women with estrogen receptor–positive breast cancer, adjuvant endocrine treatment with aromatase inhibitors improved disease-free survival compared with tamoxifen. However, pharmacogenomic data suggest that the clinical benefit of tamoxifen may vary with the number of mutant alleles of the gene that encodes CYP2D6, the cytochrome P450 isoform that is mainly responsible for catalyzing the conversion of tamoxifen to its functional metabolite endoxifen. Punglia et al. (p. 642) constructed a decision-analytic model using data from CYP2D6 pharmacogenomic studies and used it to evaluate whether an aromatase inhibitor or tamoxifen is the optimal initial treatment choice for postmenopausal women who do not carry a CYP2D6 mutation that affects tamoxifen metabolism. Their modeling suggests that among patients with wild-type CYP2D6, adjuvant treatment with tamoxifen may provide 5-year disease-free survival outcomes that are similar or perhaps even superior to those achieved with aromatase inhibitors. They conclude that endocrine therapy tailored to CYP2D6 genotype could be considered for women who are newly diagnosed with breast cancer, particularly those concerned about either the relative toxicity or higher cost of aromatase inhibitors.
In an editorial, Hayes et al. (p. 610) discuss how pharmacogenetics—the use of inherited germline differences between patients to predict cancer outcomes and toxic effects of specific therapies—is influencing the choice of targeted therapies for women with breast cancer. Both tumor-related somatic changes and inherited pharmacogenetic factors will likely predict the best course of treatment for a specific patient.
Resistance of Tumorigenic Breast Cancer Cells to Chemotherapy
Tumorigenic breast cancer cells that express high amounts of CD44 and low or undetectable amounts of CD24 can be isolated from breast cancer biopsies and grown in vitro as three-dimensional mammospheres. To compare the effects of conventional chemotherapy and the epidermal growth factor receptor inhibitor lapatinib on tumorigenic breast cancer cells, Li et al. (p. 672) isolated cells from biopsy samples of HER2-negative breast cancer patients who were treated with conventional chemotherapy and of HER2-positive patients who were treated with lapatinib. They compared the number of tumorigenic cells before and after treatment. After chemotherapy, the percentage of tumorigenic cells and mammosphere formation increased, whereas after lapatinib treatment, both slightly decreased. The authors conclude that these tumorigenic cells are resistant to chemotherapy and that the combination of conventional chemotherapy with targeted therapy may reduce the number of tumorigenic cells, reduce recurrence and improve long-term survival.
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Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 622-629.
J Natl Cancer Inst 2008 100: 642-648.
J Natl Cancer Inst 2008 100: 663-671.
J Natl Cancer Inst 2008 100: 630-641.
J Natl Cancer Inst 2008 100: 649-662.
J Natl Cancer Inst 2008 100: 672-679.
J Natl Cancer Inst 2008 100: 610-613.
J Natl Cancer Inst 2008 100: 605-606.
J Natl Cancer Inst 2008 100: 607-610.
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