© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 3, 197,
February 3, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
How aggressively should physicians treat dysplasia of the uterine cervix? The answer depends on the natural history of the disease—that is, how often different forms of dysplasia return to normal or progress to cancer. Because treatment is now standard for most forms, Holowaty et al. (p. 252) analyzed the progression and regression of dysplasias among women whose Pap smears were analyzed by a large Canadian cytopathologic laboratory during 1970-1980 (an era of more conservative treatment) and linked the cytopathologic data with provincial cancer, hysterectomy, and mortality data. The researchers found that both mild and moderate dysplasias were more likely to regress than to progress. Because the risk of progression from moderate dysplasia was between the risks for mild and severe dysplasia, the authors suggest that moderate dysplasia may represent a clinically useful distinction.
In an editorial, Critchlow and Kiviat (p. 200) note that how best to identify women with high-grade squamous intraepithelial lesions and how to follow women found to have mild dysplasia have become increasingly complex. The editorialists say that the paper by Holowaty et al. leaves little doubt that most mild dysplasias spontaneously regress to normal and that most of them could be followed by repeated routine cytologic screening without immediate referral for colposcopy and biopsy. In addition, the editorial writers say that the article by Palefsky et al., also in this issue (p. 226), suggests that measures of immune function may be useful in identifying human immunodeficiency virus-1-positive women at high risk of sustained infection with human papillomavirus and, hence, of developing cervical cancer.
Risk of HPV Infection
Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus (HIV)-1. To determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women, Palefsky et al. (p. 226) characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study. Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, e.g., low count of CD4-positive T cells and high HIV RNA load, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.
BRCA1 and BRCA2 Mutations and Cancer Survival
Studies of survival following breast or ovarian cancer in carriers and noncarriers of mutations in the BRCA1 and/or BRCA2 genes have yielded conflicting results. In a new study, Lee et al. (p. 259) have examined survival in a large group of Ashkenazi Jewish volunteers who were screened for three important mutations in the two genes and who provided questionnaire data about the incidence of breast or ovarian cancer and survival among their first-degree relatives. The authors report that there were no survival differences following breast or ovarian cancer between the carriers and noncarriers of BRCA1 and/or BRCA2 mutations.
In an editorial, Burke and Laya (p. 201) note that the findings of Lee et al. add weight to the evidence indicating a generally similar cancer course in carriers and noncarriers of mutations. They say, however, that there may be modifying factors that may influence the clinical effect of the mutations; a full understanding of the clinical implications of mutations in these genes will require studies that evaluate both the mutations and the factors that modify their expression.
Estrogen Replacement Therapy and Breast Cancer Survival
Hormone replacement therapy (HRT) for menopause appears to increase the risk of breast cancer in women, but some studies suggest that the therapy is associated with a reduction in mortality from the disease. Schairer et al. (p. 264) examined breast cancer mortality among postmenopausal women diagnosed with breast cancer during a large, national breast cancer screening program. The researchers found that women who were current users of HRT at diagnosis had statistically significant lower rate ratios for breast cancer mortality than nonusers of hormone therapy—until 144 months after diagnosis for women with axillary lymph node-negative disease (but not thereafter) and until 48 months for current and past hormone users with lymph node-positive disease (but not thereafter). The authors note that further studies are needed to identify the factors underlying these mortality differences.
Prognostic Indicator for Node-Negative Breast Cancer
Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. In this issue, Rudolph et al. (p. 271) introduce a new monoclonal antibody that they believe can be used as an accurate prognostic indicator for this disease. The monoclonal antibody, named Ki-S2, binds to a nuclear protein that is expressed in proliferating cells only in S, G2, and M phases of the cell cycle. By determining the percent of Ki-S2-labeled nuclei in tumor specimens, the authors were able to distinguish those tumors that contained many proliferating cells, and thus posed a high risk of mortality, from those tumors that did not. The authors suggest that measurement of Ki-S2 binding to a tumor specimen may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy.
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