© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 24, 2063,
December 15, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
The conventional treatment for oropharyngeal cancer, radiation therapy, is not very successful. To test the ability of chemotherapy given concomitantly with radiotherapy to improve the outcome in this disease, Calais et al. (p. 2081) studied 226 patients enrolled in a randomized, phase III clinical trial. The trial compared radiotherapy alone with combined ther-apy using carboplatin and 5-fluorouracil with radiation treatment. The patients were followed for a mean of 35 months, and all patients were followed for at least 12 months. Although patients receiving both radiotherapy and chemotherapy over a period of 7 weeks exhibited a significantly increased rate of high-grade acute toxicity (71% versus 39% for patients receiving radiation therapy alone), 3-year overall survival and disease-free survival for the combined-therapy group (51% and 42%, respectively) were significantly higher than for patients who received only radiotherapy (31% and 20%, respectively).
In an accompanying editorial, Forastiere and Trotti (p. 2065) place the results of the study by Calais et al. in the context of other combined radiation therapy and chemotherapy (radiochemotherapy) trials and meta-analyses for head and neck cancer. The editorialists conclude that the evidence now supports radiochemotherapy as a standard of care; however, they note that both nonsurgical and surgical approaches to organ conservation need to be evaluated with attention to assessments of speech and swallowing function in addition to local control and survival outcomes.
TGF-ß and Breast Cancer Risk
Transforming growth factors-ß (TGF-ßs) are potent growth suppressors that regulate breast cell proliferation. They do this through the TGF-ß receptor type II (TGF-ß-RII) on the cell surface. Epithelial hyperplasia lacking atypia (EHLA) is a common benign breast abnormality that is associated with a mild elevation in breast cancer risk. Gobbi et al. (p. 2096) studied the expression of TGF-ß-RII in patients with EHLA. Patients with 25%-75% of normal TGF-ß-RII expression had a 1.98 times greater risk of developing invasive breast cancer than did women with normal expression; those with less than 25% of normal were at a 3.41 times greater risk. The investigators conclude that the loss of TGF-ß-RII expression is associated with an increased risk of invasive breast cancer.
In an editorial, Ellis and Hayes (p. 2067) note that EHLA is generally ignored by clinicians because the relative increased risk of breast cancer associated with such lesions is modest. Tamoxifen treatment of all women with EHLA would result in an enormous number of patients needlessly taking the drug, they say. Ellis and Hayes suggest that loss of TGF-ß-RII expression in EHLA may provide a means to identify patients at increased risk who may be considered for chemoprevention.
ß-Carotene Supplementation
Individuals with high intakes of fruits and vegetables containing ß-carotene seem to experience lower risks of developing cancer, as determined by epidemiologic methods. However, the few randomized trials of ß-carotene supplementation show no overall benefits; some even suggest harm. Lee et al. (p. 2102) tested the effects of ß-carotene in healthy women participating in the Women's Health Study. This is a randomized, double-blind, placebo-controlled trial originally testing aspirin, vitamin E, and ß-carotene in the prevention of cancer and cardiovascular disease among 39,876 apparently healthy women aged 45 years or older. The ß- carotene component was terminated early after a median treatment duration of 2.1 years. No effect was found on the incidence of cancer, cardiovascular disease, or mortality after a median of 4.1 years (treatment plus follow-up). The authors conclude that there was no benefit or harm among these women from ß-carotene supplementation for a limited period.
In an editorial, Marshall (p. 2068) explores possible reasons for epidemiology's "miss." He points out that there is a need to attend to possible imprecision and confounding in the dietary data on which much of nutritional epidemiology relies.
HRAS1 Alleles and Breast Cancer
It has been hypothesized that women who lack one of the four common minisatellite alleles at the HRAS1 locus are at increased risk for breast cancer. Firgaira et al. (p. 2107) have tested this hypothesis by use of a new method to size minisatellite alleles in a group of Australian women with early-onset breast cancer. The authors found no association between the HRAS1 rare alleles and the risk of breast cancer in this group. They recommend that this hypothesis be retested with new methods that can more clearly distinguish rare alleles from similarly sized common alleles.
BRCA1/BRCA2 Mutations
The inherited founder mutations in the BRCA1 and/or BRCA2 genes are associated with an increased risk of breast cancer. However, whether patients with breast cancer who have such mutations have an outcome different from that of patients with "sporadic" breast cancer has been unresolved. To address this question, Robson et al. (p. 2112) compared the outcomes after breast conservation therapy in Ashkenazi women with or without inherited mutations in BRCA genes. They report that patients with BRCA mutations are more likely to experience distant relapse and die of breast cancer. In spite of this finding, mutation status was not an independent predictor of survival, suggesting that other factors are involved.
Rescue From Tamoxifen Failure
In many cases, breast cancers stop responding to the antihormonal agent tamoxifen after initially regressing. To investigate the possibility of using LGD1069, a retinoid X receptor-specific ligand, in the treatment of breast cancers that have stopped responding to tamoxifen, Bischoff et al. (p. 2118) used a rat model of carcinogen-induced mammary carcinoma. After tamoxifen failure (i.e., a failure to respond completely) had been demonstrated in the model, they tested the effect of treatment with the ligand in combination with tamoxifen versus treatment with tamoxifen alone. The researchers found that LGD1069 plus tamoxifen given for up to 20 weeks after tamoxifen failure produced an overall objective response rate of 94% (includes complete responses and partial responses), compared with a rate of 33% for tamoxifen alone. They also found that tumors that failed to respond to tamoxifen therapy exhibited a 51% objective response rate to the LGD1069 in the absence of further tamoxifen.
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