© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 2, 79,
January 17, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Uncertainty about prognosis and treatment of axillary lymph node-negative patients with estrogen receptor (ER)-negative or ER-positive breast cancers of 1 cm or less prompted Fisher et al. (p. 112) to analyze data from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. They looked at relapse-free survival (RFS) and overall survival after 8 years of follow-up. Women with ER-negative tumors who received either surgery or surgery and chemotherapy had similar overall survival; however, those who also received chemotherapy had better RFS (81% versus 90%). Women with ER-positive tumors received surgery alone, addition of tamoxifen, or addition of tamoxifen and chemotherapy; RFS was 86%, 93%, and 95%, respectively, and survival was 90%, 92%, and 97%, respectively. The authors conclude that chemotherapy and/or tamoxifen should be considered for the treatment of women with ER-negative or ER-positive tumors of 1 cm or less and negative axillary lymph nodes.
In an editorial, Lippman and Hayes (p. 80) discuss other factors to consider before recommending adjuvant therapy for patients with breast cancer. They conclude that we need more research to identify strong prognostic factors that can identify patients with tumors less than 1 cm for whom the benefits of adjuvant therapy far outweigh the risks.
Radiation Damage and Skin Biomarkers
When DNA in cultured cells is damaged by UVA, UVB, or 
-radiation, intracellular levels of p53 and p21 proteins increase. Ponten et al. (p. 128) analyzed data from a randomized clinical trial to determine whether this response occurred in human skin and was associated with radiation dermatitis. They found increased levels of both p53 and p21 in irradiated skin, a few p53-positive cells in normal skin, and large interindividual differences in the p53 response. Individuals who reacted strongly to one type of radiation also reacted strongly to others. Despite this variation, comparable increases in p53 were independent of the type of radiation used. The p53 response in irradiated skin, however, did not predict the degree of radiation dermatitis. The authors urge additional study of in vivo mechanisms regulating the p53 response to DNA damage and the role of p53 in normal cells.
In an accompanying editorial, Ljungman (p. 82) emphasizes the importance of the great variability among individuals in p53/p21 responsiveness to both UV and ionizing radiation. Individuals with a strong response to UV reacted strongly to ionizing radiation and vice versa, an observation that he believes should be further investigated to determine its association with cancer susceptibility and prognostic utility in other tissues.
Estimated Nicotine Intakes and Toxin Exposure in Smokers
The relevance of nicotine yields from machine-smoked cigarettes for quantifying smokers’ nicotine intakes and exposure to cigarette toxins has been questioned. Jarvis et al. (p. 134) examined the relationship between nicotine yields of machine-smoked cigarettes and salivary cotinine (a major metabolite of nicotine) concentrations in a nationally representative sample of 2031 adult smokers of manufactured cigarettes surveyed in the 1998 Health Survey for England. Cotinine concentrations varied widely between smokers at any level of nominal brand nicotine yield. Estimated nicotine intake per cigarette smoked did not correspond with machine-smoked deliveries at any level of nicotine yield; estimates were about eight times higher than the lowest nicotine deliveries from machine smoking and 1.4 times higher at the highest deliveries. The authors conclude that smokers’ tendency to regulate nicotine intake vitiates the potential health gains from lower tar and nicotine intake.
"Our findings reinforce the emerging consensus that current approaches to characterizing tar and nicotine yields of cigarettes are simplistic and misleading to consumers and regulators alike and should be abandoned."
—Jarvis et al.
Breast Cancer Risk in Ataxia-Telangiectasia Carriers
Individuals with the recessive genetic neurologic disorder ataxia-telangiectasia (A-T) have an increased risk of cancer. Although heterozygous carriers of a mutation that causes A-T appear normal, some epidemiologic studies have suggested that carriers also have an increased risk of female breast cancer. However, other studies have not found such an association. To try to resolve this question, Olsen et al. (p. 121) studied the incidence of cancer in the relatives of A-T patients in the Nordic countries, which have high-quality population registries that record the occurrence of cancer. Overall, heterozygous carriers had a more than twofold increased risk of breast cancer. Mothers of the A-T patients, who are obligate carriers, had a sevenfold increased risk; however, the risk was not increased in relatives who were less likely to be mutation carriers (e.g., sisters, grandmothers, and aunts). The authors note that genotyping might clarify these apparently contradictory findings.
In an accompanying editorial, Swift (p. 84) reviews the evidence that carriers of a mutation that causes A-T have an increased risk of breast cancer. He notes that reliable estimates of the frequency of heterozygous carriers among breast cancer patients and the general population will require sensitive mutation screening methods, especially given the large size of the gene.
Quality of Informed Consent
Investigators are ethically and legally required to obtain informed consent from subjects before they enroll in clinical trials. There are federal regulations regarding consent to research participation, as well as guidance from the National Cancer Institute regarding consent forms. Nevertheless, the quality and outcome of the informed consent process can vary dramatically. Joffe et al. (p. 139) have developed a questionnaire to evaluate the quality of informed consent to cancer clinical research. This questionnaire is a simple, reliable, generic measure that assesses both the objective and subjective understanding of participants in diverse clinical trials. The authors conclude that this questionnaire holds promise as a way to standardize the study of informed consent to research and ultimately to improve the quality of subjects’ consents.
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