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© Oxford University Press 2007.
IN THIS ISSUE
Transdermal Testosterone and Libido in Female Cancer SurvivorsFemale cancer survivors may suffer from low libido and other changes in sexual function. In previous trials, a combination of transdermal testosterone and estradiol has been shown to improve libido in women with low libido. To determine whether transdermal testosterone alone could benefit cancer survivors, Barton et al. (p. 672) measured serum testosterone levels and changes in sexual function reported by postmenopausal women who were cancer survivors. The participants were randomly assigned to transdermal testosterone or placebo in a randomized controlled trial with a crossover design. Although their testosterone levels increased during the treatment period, the women who received testosterone reported no greater change in libido than those taking a placebo. The authors conclude that the treatment may have not worked because the women in the trial were not given supplemental estrogen and had low levels of estrogen, unlike the women in the previous trials who had sufficient estrogen.
In an editorial, Ganz and Greendale (p. 659) discuss the multifaceted nature of female sexual function, the context for interpretation of the study of Barton et al. regarding treatment of female patients with low libido, and the design of future studies.
Drug Resistance and Genetic Instability in CML Stem Cells
Imatinib therapy that targets the BCR-ABL oncogene has been effective in causing remissions in patients with chronic-phase chronic myeloid leukemia, but relapses often occur. Jiang et al. (p. 680) analyzed the BCR-ABL oncogene in chronic myeloid leukemia stem cells obtained from patients who had not received imatinib. They found that the oncogene was highly susceptible to genetic mutation both in vivo and in vitro. The authors conclude that the inherent genetic instability of chronic myeloid leukemia stem cells may explain the tendency of patients to develop resistance to therapies that target the BCR-ABL oncogene.
In an accompanying editorial, Rodrigues and Sattler (p. 662) discuss the possible causes of genetic instability in chronic myeloid leukemia stem cells and the implications of the new findings for ongoing efforts to develop improved therapies for the disease.
HER2-Overexpressing Breast Cancer and Multiagent Targeted Treatment
HER inhibitors only partially block HER signaling and tumor growth in xenograft breast cancer models. Arpino et al. (p. 694) investigated whether a blockade of signaling from HER with several inhibitors could more effectively block tumor growth in such models. The tumors of mice treated with single agents or dual-agent combinations, even in the presence of antiestrogen therapy, eventually progressed. Most tumors of mice treated with gefitinib, trastuzumab, and pertuzumab plus tamoxifen or plus estrogen withdrawal disappeared completely and did not reappear for more than 189 days after treatment. The authors conclude that treatment with three HER inhibitors blocked growth of HER2-overexpressing xenografts better than treatment with a single agent or two-drug combinations.
Rituximab, Chemotherapy, and Overall Survival in Lymphoma Patients
Adding the anti-CD20 monoclonal antibody rituximab to chemotherapy (R-chemo) improves response rates and progression-free survival in patients with indolent or mantle cell lymphoma, but the impact of R-chemo on overall survival is unclear. To examine the efficacy of R-chemo compared with chemotherapy alone, Schulz et al. (p. 706) performed a systematic review and meta-analysis of seven randomized controlled trials that included 1,943 patients. Patients treated with R-chemo had better overall survival (particularly patients with follicular lymphoma), overall response, and disease control but were more likely to have fever and fewer circulating white blood cells than patients treated with chemotherapy alone. The authors conclude that initial therapy with rituximab and chemotherapy is superior to chemotherapy alone with respect to overall survival in patients with indolent or mantle cell lymphoma.
New Risk Prediction Models for Lung Cancer
Risk prediction models could play an important role in cancer research and prevention. The ability to assess individual risk allows for targeted prevention efforts and improves identification of appropriate patients to include in certain types of clinical trials. Several models for lung cancer risk prediction exist, but these focus mainly on long-term smokers and largely include smoking variables. Using data from a large case–control study of lung cancer, Spitz et al. (p. 715) developed and validated separate models for lung cancer risk prediction among never, former, and current smokers. The predictive factors in the models—which included exposure to secondhand smoke, asbestos, and dust; family history of cancer; smoking history variables; and prior respiratory disease—all have biologically plausible roles in lung cancer. The authors used the models to calculate absolute risks of lung cancer for the different smoking populations and also to create an ordinal risk index. They conclude that these risk prediction models could be valuable tools in risk assessment because they use easy-to-obtain clinical information.
Long-term Results of Tamoxifen Treatment Trial to Prevent Breast Cancer
Initial findings from the Italian Randomized Tamoxifen Prevention Trial showed no reduction in breast cancer risk, in contrast to the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (P-1), which showed a benefit for women at high risk for breast cancer. In a longer follow-up study, the women in the Italian trial were grouped by baseline risk for hormone receptor–positive breast cancer; all had undergone a hysterectomy before the trial began. After 11 years of follow-up, Veronesi et al. (p. 727) found that tamoxifen treatment reduced breast cancer incidence among women at high risk (1.51 vs. 6.26 per 1,000 women-years). There was not a statistically significant effect on risk overall or among women who were in the low risk group. Women who took tamoxifen reported side effects, including hot flashes and cardiovascular events, more often than women who took placebo. The authors conclude that tamoxifen is a useful intervention for women at high risk for breast cancer.
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Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 659-661.
J Natl Cancer Inst 2007 99: 662-663.
J Natl Cancer Inst 2007 99: 672-679.
J Natl Cancer Inst 2007 99: 680-693.
J Natl Cancer Inst 2007 99: 694-705.
J Natl Cancer Inst 2007 99: 706-714.
J Natl Cancer Inst 2007 99: 715-726.
J Natl Cancer Inst 2007 99: 727-737.
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