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© Oxford University Press 2008.
IN THIS ISSUE
Sorafenib Targets Mutant FLT3 in Acute Myelogenous LeukemiaThe kinase inhibitor sorafenib induces growth arrest and apoptosis at much lower concentrations in acute myeloid leukemia (AML) cell lines that harbor internal tandem duplication (ITD) mutations in a section of the Fms-like tyrosine kinase 3 (FLT3) gene than in those with wild-type FLT3. Zhang et al. (p. 184) examined the anti-leukemic activity of sorafenib in mouse AML cell lines that expressed mutant or wild-type FLT3, human AML cells, a mouse leukemia xenograft model, and 16 AML patients with known FLT3 gene mutation status who were treated with sorafenib in a phase I clinical trial. Sorafenib preferentially induced growth arrest and apoptosis in FLT3-ITD mutant mouse AML cells, prolonged survival of mice bearing FLT3-ITD xenografts, and reduced the percentage of leukemia blasts in the peripheral blood and bone marrow of AML patients who harbored FLT3-ITD mutations. The authors conclude that sorafenib may have therapeutic efficacy in AML patients whose cells harbor FLT3-ITD mutations.
Endogenous Sex Hormones and Prostate Cancer Risk
An association between sex hormones in serum and the risk of prostate cancer has been proposed. The Endogenous Sex Hormones and Prostate Cancer Collaborative Group (p. 170) performed an analysis of existing epidemiologic data from worldwide studies to investigate this relationship. They found no association between prostate cancer risk and serum concentrations of almost all hormones tested. Increased serum concentration of sex hormone binding globulin was modestly associated with reduced prostate cancer risk. No heterogeneity among studies was found, and adjusting for potential confounders had little effect. The authors conclude that serum concentrations of sex hormones were not associated with the risk of prostate cancer.
In an editorial, Carpenter et al. (p. 158) note that this study, by confirming the lack of evidence to support the androgen–prostate cancer etiology hypothesis, obliges the scientific community to move past elevated androgen levels as a risk factor for prostate cancer. They suggest that researchers get on with the difficult task of finding, analyzing, and characterizing modifiable risk factors for prostate cancer.
Surgeon and Patient Attributes and Radiotherapy for Breast Cancer
Radiotherapy following breast conservation surgery reduces the risk of local recurrence in women with breast cancer, but not all women receive this treatment. Hershman et al. (p. 199) used data from the Surveillance, Epidemiology, and End Results program; Medicare; and the American Medical Association to examine relationships between surgeon and patient characteristics and the likelihood of receiving radiotherapy after breast conservation surgery. Patients whose surgeons were female, trained in the United States, and had an M.D. degree were more likely to receive radiotherapy. Patients receiving radiotherapy also tended to be younger, white, married, and living in an urban area. The authors stress the need for further research to confirm these associations and to determine whether they are based on surgeon behavior, patient characteristics, or patient–physician interactions.
Ki-67 Expression and Response to Breast Cancer Adjuvant Therapy
Some studies have suggested that breast cancer tumors with a high percentage of cells with an antibody against the proliferation antigen Ki-67 have a better response to primary chemotherapy. Viale et al. (p. 207) retrospectively assessed Ki-67 expression in tumor tissue from 1,924 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemotherapy and endocrine therapy versus endocrine therapy alone for node-negative breast cancer. A high Ki-67 level was associated with other factors that predict poor prognosis. Among patients with endocrine-responsive tumors, a higher Ki-67 level was associated with worse disease-free survival, but Ki-67 level did not predict which women would benefit from combined chemotherapy and endocrine therapy compared with endocrine therapy alone.
In an editorial, Ellis (p. 159) notes that these findings support the long-held position of the American Society of Clinical Oncology Tumor Markers Expert Panel that measurements of the cell cycle should not be used to make decisions about chemotherapy. He discusses the need for assays that integrate more biologic parameters than just the baseline rate of cell cycle progression to predict chemotherapy sensitivity in hormone receptor–positive breast tumors.
Personality Factors and Risk of Breast Cancer
Associations between personality factors and the development of breast cancer have been inconsistent. Bleiker et al. (p. 213) analyzed data from a prospective longitudinal study 5–13 years after participants completed a baseline questionnaire on personality factors. After a short follow-up of 2 weeks to 5 years, the authors previously reported that only one of 11 personality factor was weakly associated with the development of breast cancer. But after the additional follow-up, none of the 11 personality factors, alone or in combination, were statistically significantly associated with the development of breast cancer. The authors conclude that these findings may assist oncologists to reassure patients that personality appears to have no role in the development of breast cancer.
ER Results from Pathology versus Central Laboratory
Breast cancer clinical trials often use estrogen receptor (ER) results from pathology reports instead of assaying the specimens again in a central laboratory, but the reliability of these data is unclear. Collins et al. (p. 218) compared ER assay results abstracted from pathology reports with immunohistochemical results on the same specimens from central laboratory testing to determine their rate of agreement. They found that these results were in agreement for 87.3% of all specimens and for 92.3% of specimens for which the original assay was immunohistochemical. The authors conclude that ER assay results from pathology reports appear to be a reasonable alternative to central laboratory testing for large population-based studies of patients with breast cancer.
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Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 218-221.
J Natl Cancer Inst 2008 100: 213-218.
J Natl Cancer Inst 2008 100: 207-212.
J Natl Cancer Inst 2008 100: 199-206.
J Natl Cancer Inst 2008 100: 170-183.
J Natl Cancer Inst 2008 100: 159-161.
J Natl Cancer Inst 2008 100: 184-198.
J Natl Cancer Inst 2008 100: 158-159.
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