© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 12, 957,
June 21, 2000
© 2000 Oxford University Press
IN THIS ISSUE |
Bobo et al. (p. 971) analyzed data from 752,081 clinical breast examinations (CBEs) from the National Breast and Cervical Cancer Early Detection Program to determine the percentage of CBEs considered abnormal (suspicious for cancer), the rates of cancer detection, and the sensitivity and specificity of CBEs. They report that 6.9% (about one in 15) of all CBEs were coded as abnormal, and they found that five cancers were detected per 1000 CBEs. They determined that the sensitivity and specificity were comparable to those reported for the CBE component of clinical trials. The authors conclude that CBEs done in a community-based screening program can detect breast cancers as effectively as those done in clinical trials.
In an accompanying editorial, Baines (p. 958) compares the results of Bobo et al. with other studies and concludes that their results show that CBE can do quite well under relatively uncontrolled conditions in a community setting. She points out, however, that we still need to know what high-quality CBE could achieve in the same setting.
Vitamin A, N-Acetylcysteine, and Tumor Recurrence
van Zandwijk et al. (p. 977) report the results of EUROSCAN, a large randomized intervention study to determine whether vitamin A (retinyl palmitate) and N-acetylcysteine (an antimutagen that inhibits formation of carcinogen–DNA links) could improve the prognosis of patients with lung cancer or head and neck cancer by preventing second primary tumors. These patients were a high-risk population for both second primary tumors and tumor recurrence and were predominantly previous or current smokers. Patients were randomly assigned to receive vitamin A, N-acetylcysteine, both compounds, or neither compound. The authors found that 2-year treatment with vitamin A and/or N-acetylcysteine resulted in no benefit in terms of survival, event-free survival, or second primary tumors for these patients. However, because carcinogenesis is a multistep process, the authors recommend that subjects in cancer prevention trials such as EUROSCAN be followed for at least 10 years to reach definite conclusions.
In an accompanying editorial, Omenn (p. 959) notes that, unlike important successes with selective estrogen receptor modulators for breast cancer and nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for the colon, results of randomized large-scale chemoprevention trials against lung cancer have been disappointing. Despite these results, he predicts that there will be advances in chemoprevention from new molecular approaches and better identification of patient and population subgroups.
"The strategy of relying on low-cost vitamins and existing pharmaceuticals [as potential cancer chemoprevention agents] reflects . . . the desire to have cost-effective approaches for the general population."
—Omenn
c-erbB2 and Chemosensitivity
Studies of breast cancer patients have linked overexpression of the gene c-erbB2 with either increased or decreased response to cancer therapies. Whether the gene itself is responsible for observed differences in chemosensitivity, however, is not known. Orr et al. (p. 987) modified normal human mammary epithelial cells—avoiding some of the complexity associated with using cancer cells—to overexpress c-erbB2 and tested the cells’ sensitivity to several chemotherapeutic agents. They found no change in sensitivity to a panel of chemotherapeutic agents in modified cells compared with unmodified cells, even when the cell population was purified to reduce the effect of cells not expressing c-erbB2 on their surface. The authors conclude that expression of c-erbB2 by itself does not appear to affect chemosensitivity, control of which may ultimately prove to involve a number of genes.
Diurnal Cortisol Rhythms and Metastatic Breast Cancer
Abnormal circadian rhythms have been observed in patients with cancer. Sephton et al. (p. 994) examined the prognostic value of diurnal variation of salivary cortisol (a major natural glucocorticoid that affects the immune system) in patients with metastatic breast cancer. They also studied the relationships between cortisol rhythms, circulating natural killer (NK) cells and their activity, standard prognostic indicators, and other variables. Compared with patients who had a normal rhythmic cortisol pattern, earlier mortality occurred among patients with relatively "flat" rhythms, indicating a lack of normal diurnal variation. Flattened profiles were linked with low NK cell counts and reduced NK activity. The cortisol slope appeared to be an independent predictor of survival, and NK cell count was a secondary predictor of survival. The authors speculate that disruption of the cortisol cycle may be one mediator of more rapid disease progression.
-Fetoprotein and Maternal Breast Cancer
Women who have had a full-term pregnancy appear to have a reduced risk of developing breast cancer. To understand the underlying biologic mechanism for this observation, Melbye et al. (p. 1001) analyzed records of 42,057 pregnant Danish women enrolled in an -fetoprotein-screening program. Of these women, 117 were diagnosed with breast cancer. The authors found that, compared with women with -fetoprotein levels below the median, women with an -fetoprotein level greater than or equal to the median value had a 41% lower risk of breast cancer and, in particular, a low incidence of aggressive breast cancer. Their most striking finding was that women with high levels of serum -fetoprotein had a particularly reduced incidence of larger tumors. They conclude that these findings may offer an explanation as to why the risk of breast cancer is lower in women who have had a full-term pregnancy compared with women who have not.
"The association between high -fetoprotein levels in maternal serum and a reduced incidence of breast cancer was particularly strong among women with a pregnancy at a young age."
—Melbye et al.
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