© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 21, 1585,
November 7, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Reports that the relative risk of cancer in smokers compared with nonsmokers is greater in women than in men have led to considerable speculation about the biologic mechanisms involved. It has also led to many news stories that echo these results. In his commentary, Perneger (p. 1600) suggests that evidence from many epidemiologic studies is interpreted incorrectly because of misunderstandings about the meanings of relative risk versus absolute risk and the meanings of statistical interaction versus biologic interaction. Correcting the first issue, misinterpretation of relative risk estimates, he believes, may require epidemiologic training, cautious interpretation of results, and careful proofreading of manuscripts before submission and after editing. Correcting the second issue, the misunderstanding of interaction (statistical or biologic), he believes, is more difficult to achieve and may require a new nomenclature.
Tamoxifen and Depression
Concerns have been raised that tamoxifen treatment may be associated with episodes of depression. Day et al. (p. 1615) examined the psychological effects of tamoxifen treatment on 11,064 women at different levels of risk for clinical depression who were enrolled in the National Surgical Adjuvant Breast and Bowel Project’s Breast Cancer Prevention (P-1) study. Each woman was prospectively assessed for the risk of depression and assigned to a high-, medium-, or low-risk group. After evaluating the women every 6 months with the Center for Epidemiological Studies—Depression scale (CES-D), the authors found that there was a positive relationship between depression risk and CES-D scores, with those in the high-risk group being the most likely to experience a depressive episode. However, within the risk groups, there was no difference in CES-D scores between women receiving tamoxifen and those receiving the placebo. The authors conclude that tamoxifen does not increase the risk for or exacerbate existing depression in women.
Ductal Lavage for Detecting Atypical Breast Cancer Cells
Women with atypical ductal epithelial breast cells have a higher risk of breast cancer than women with normal breast cells. In a prospective multicenter study, Dooley et al. (p. 1624) compared the abilities of ductal lavage, a new procedure for collecting cells from milk ducts with a microcatheter, with nipple aspiration to detect abnormal breast epithelial cells in women at high risk for breast cancer. They found that ductal lavage collected substantially more breast epithelial cells than nipple aspiration and that abnormal cells were detected 3.5 times more often in samples collected by ductal lavage than in samples collected by nipple aspiration. The authors also report that ductal lavage is a safe and well-tolerated procedure.
Prophylactic Mastectomy in BRCA1/2 Mutation Carriers
Although prophylactic mastectomy is associated with a substantially reduced risk of subsequent breast cancer in women with a family history of the disease, the effect in women who carry mutations in their BRCA1 and BRCA2 genes is unclear. Hartmann et al. (p. 1633) determined the BRCA1 and BRCA2 gene mutation status of 214 women with strong family histories of breast cancer who had previously undergone prophylactic mastectomy. They found that none of the 26 women with a mutation in BRCA1 or BRCA2 developed breast cancer. Of the three women who developed breast cancer following prophylactic mastectomy, two were screened for BRCA1 or BRCA2 mutations and were negative. The mutation status of the third woman could not be determined. The authors estimated the mutation carriers’ probabilities of developing breast cancer and calculated a risk reduction, after bilateral prophylactic mastectomy, of 89.5% to 100%. They conclude that the risk reduction after prophylactic mastectomy in BRCA1 and BRCA2 carriers is substantial, even in this highest-risk group.
In an editorial, Lynch et al. (p. 1586) discuss the historical context for the use of prophylactic mastectomy in women at high risk for breast cancer, examine how the knowledge of BRCA1 or BRCA2 mutation status may affect the decision to undergo the procedure, and identify persisting barriers that prevent women from choosing prophylactic surgical procedures.
CCR7 and Regional Lymph Node Metastasis
CC chemokine receptor-7 (CCR7) is involved in dendritic cell migration to regional lymph nodes through afferent lymphatic vessels. Because CCR7 is also expressed by human breast and melanoma cell lines, Wiley et al. (p. 1638) investigated whether CCR7 expression would enhance metastasis of B16 melanoma cells to regional lymph nodes by inserting CCR7 complementary DNA into B16 cells (CCR7-B16 cells) so that they express CCR7. When CCR7-B16 cells were injected into the footpad of mice (so that cells used a lymphatic route), 58% of the lymph nodes showed gross metastases compared with 5% in mice injected with control B16 cells. When injected intravenously (so that cells used a vascular route), both cell types metastasized equally well to the lung. They conclude that expression of a single CCR7 gene increased B16 cell metastasis to draining lymph nodes by co-opting normal mechanisms of lymph node homing.
In an editorial, Förster et al. (p. 1588) provide additional background information about CCR7 and highlight the remarkable finding that expression of a single gene, CCR7, enabled melanoma cells to acquire new metastatic properties. They urge that additional research should examine other changes induced by the expression of CCR7 in B16 cells and should explore the mechanism of the newly acquired properties.
Insights From Lung Cancer in Sheep
Although smoking is the leading cause of lung cancer, many cases of lung cancer are not associated with smoking, and the incidence of lung adenocarcinoma, a subtype less often associated with smoking, is increasing. In hopes of finding insights from animal models of lung cancer, Palmarini and colleagues have studied ovine (sheep) pulmonary adenocarcinoma (OPA), which is caused by a retrovirus with a particular affinity for the differentiated epithelial cells of the lung. In a review in this issue of the Journal (p. 1603), they discuss the literature on OPA, examine similarities between sheep and human lung cancers, and explore ways that OPA and its retrovirus can shed light on mechanisms and causes of human lung adenocarci
| ||||||||||||||||||||||||||||||||||||