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© Oxford University Press 2007.
IN THIS ISSUE
Results from Adjuvant Breast Cancer Randomized TrialsPatients with early-stage breast cancer have an improved outcome after a single treatment with tamoxifen, ovarian ablation or suppression, or chemotherapy. The Adjuvant Breast Cancer Trials were initiated to determine whether 5 years of tamoxifen treatment, combined with chemotherapy and/or ovarian ablation or suppression, would further improve outcomes. In the chemotherapy trial reported by Bliss et al. (p. 506), 1,991 women with early-stage breast cancer were randomly assigned between 1992 and 2000 to receive chemotherapy. The women could have undergone ovarian ablation or suppression or not. The addition of chemotherapy to tamoxifen improved relapse-free and overall survival compared with no chemotherapy; women younger than 50 years and premenopausal women who did not receive ovarian ablation or suppression showed the greatest benefit.
In the ovarian ablation or suppression trial (p. 516), 2,144 pre- and perimenopausal women with early-stage breast cancer were randomly assigned between 1993 and 2000 to receive ovarian ablation or suppression. The women could have received chemotherapy or not. Ovarian ablation or suppression did not improve relapse-free or overall survival compared with tamoxifen alone.
The authors conclude that, overall, women with early-stage breast cancer may have modest and sustainable benefits from combined chemotherapy and endocrine therapy, but the real impact on overall survival may not be evident for several years. Further study is required to examine the potential benefits of ovarian ablation or suppression among women younger than 40 years with estrogen receptor–positive tumors who have not received chemotherapy.
In a related editorial, Pritchard (p. 494) discusses how the data from these trials add to current efforts to improve the outcomes of young women with early-stage breast can-cer. The studies emphasize the importance of making archived tumor specimens from all large adjuvant trials available for future biomarker analyses.
PSA Levels and Prediction of Lethal Prostate Cancer
Men with untreated localized prostate cancer have high long-term survival rates. To determine whether prostate-specific antigen (PSA) levels can be used to accurately predict which men among those with localized prostate cancer have lethal disease, Fall et al. (p. 526) performed sensitivity and specificity analyses using PSA measurements from a Scandinavian cohort of 267 men with localized prostate cancer who were being managed by watchful waiting. After a mean follow-up of 8.5 years, 52 patients had developed metastases or died from prostate cancer. Although baseline PSA values and their rates of change were associated with prostate cancer progression, neither predicted lethal disease accurately. The authors conclude that baseline PSA and rate of PSA change are prognostic factors for le-thal prostate cancer but are poor monitoring tools for patients who undergo watchful waiting.
In a related editorial, Parekh et al. (p. 496) emphasize the urgent need for better tools to predict lethal prostate cancer. Reliable prediction tools would allow doctors to avoid unnecessary treatment but to continue careful surveillance of patients with tumors that are not life-threatening. They compare the findings of Fall et al. with their own and note that there are consistent findings regarding PSA, despite important differences in study design, clinical practice, and population.
Noncancer Causes of Death in Testicular Cancer Survivors
Although modern treatment for testicular cancer is associated with increased survival, the long-term health effects of these treatments are unclear. Fosså et al. (p. 533) used data from 14 population-based cancer registries in North America and Europe to quantify the long-term risk of death from noncancer causes among 38,907 men who had survived at least 1 year after a testicular cancer diagnosis. Compared with the general population, testicular cancer patients who were treated with chemotherapy after 1975, when cisplatin-based chemotherapy came into widespread use, had a higher risk of death from all noncancer causes, notably infections, circulatory diseases, and respiratory diseases. Patients who were diagnosed before age 35 also had a higher risk of death than the general pop-ulation from all noncancer causes, including infections and circulatory diseases, regardless of treatment.
Trial of Celecoxib in Patients with Barrett's Esophagus
Barrett's esophagus, a preinvasive condition that is associated with chronic gastroesophageal reflux, is a risk factor for the development of esophageal adenocarcinoma. Because aspirin and other nonsteroidal anti-inflammatory drugs, such as celecoxib, may decrease the risk of esophageal carcinoma, Heath et al. (p. 545) conducted a phase IIb randomized, placebo-controlled trial of long-term use of celecoxib (200 mg twice daily) in patients with Barrett's esophagus and dysplasia. After 48 weeks of treatment, no difference was found in the proportion of patients with dysplasia or cancer between the celecoxib and placebo groups. The authors conclude that 200 mg of celecoxib taken twice daily for 48 weeks does not appear to prevent progression of Barrett's esophagus to cancer.
Androgen Signals and Sex in Bladder Cancer Development
Males have a higher incidence of bladder cancer than females, and males are more susceptible to the effects of bladder carcinogens. To investigate whether androgen signaling could contribute to the sex difference, Miyamoto et al. (p. 558) treated bladder cancer cell lines and mice carrying xenograft tumors derived from these lines with a variety of treatments that reduce androgen levels (i.e., antiandrogen treatment or castration) or androgen receptor activity (i.e., RNA in-terference or treatment with a molecule that leads to selective degradation of the androgen receptor). Reduction of androgen and androgen receptor levels independently suppressed cell proliferation in vitro and tumor growth in vivo. Moreover, the initiation of bladder tumors using a known bladder carcinogen was reduced in male mice whose androgen receptor had been ablated by gene targeting. The authors conclude that androgen signaling is implicated in bladder cancer development and progression. They suggest that targeting androgen signaling pathways could lead to new prevention and treatment approaches.
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Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 494-495.
J Natl Cancer Inst 2007 99: 496-497.
J Natl Cancer Inst 2007 99: 506-515.
J Natl Cancer Inst 2007 99: 516-525.
J Natl Cancer Inst 2007 99: 526-532.
J Natl Cancer Inst 2007 99: 533-544.
J Natl Cancer Inst 2007 99: 545-557.
J Natl Cancer Inst 2007 99: 558-568.
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