Other highlights of the January 15 JNCI

January 14, 2003

Study Finds Possible Mechanism for Hormone Therapy Resistance in Breast Cancer

Quantitative measurements of the expression levels of hormone receptors and the epidermal growth factor receptor HER-2/neu in women with breast cancer have shed light on possible reasons why HER-2/neu-positive breast cancer tumors are less responsive to hormone therapy compared with HER-2/neu-negative tumors. The findings appear in the January 15 issue of the Journal of the National Cancer Institute.

Breast cancer patients are typically classified as hormone receptor-positive or -negative, and response to hormone treatment such as tamoxifen has been associated with the presence of hormone receptors in breast cancer tumors. In addition, 20% to 25% of breast cancers demonstrate an amplification and overexpression of HER-2/neu. HER-2/neu-positive and hormone receptor-positive tumors seem to be less responsive to hormone treatment than hormone receptor-positive tumors that do not overexpress HER-2/neu.

To clarify the relationship between hormone receptor levels and HER-2/neu overexpression/amplification, Gottfried Konecny and Dennis J. Slamon, of the University of California at Los Angeles Jonsson Comprehensive Cancer Center, and their colleagues analyzed quantitative levels of HER-2/neu expression/amplification and hormone receptor expression in cell lines and in 1556 patients with breast cancer.

They found that, in general, higher levels of HER-2/neu overexpression or gene amplification were associated with lower corresponding hormone receptor levels. HER-2/neu amplification and overexpression were associated with lower absolute tumor hormone receptor levels, even in patients with tumors classified as hormone receptor-positive. The authors note that this phenomenon may help to explain the lower response to hormone therapy that has been reported among HER-2/neu-positive, hormone receptor-positive patients compared with HER-2/neu-negative, hormone receptor-positive patients.

The authors conclude that quantitative measurements of HER-2/neu and hormone receptors may be a better way to predict response to hormone therapy for patients with HR positive tumors that also overexpress HER-2/neu than the scoring systems commonly used.

Mutations in Gene for Rare Disease Associated with Risk of Colon Cancer

Mutations in the hereditary hemochromatosis gene (HFE) are associated with an increased risk of colon cancer, according to a new study in the January 15 issue of the Journal of the National Cancer Institute.

Hereditary hemochromatosis is an autosomal recessive disease that is characterized by iron overload, which leads to dysfunction of the pancreas, liver, heart, and other organs. Although the disease itself is rare, the HFE gene mutations that cause the disease occur in up to 15% of the U.S. population. HFE gene mutations are associated with increased total body iron stores in some people. Because high iron levels can lead to free radical formation and DNA damage, Nicholas J. Shaheen of the University of North Carolina at Chapel Hill and colleagues performed a population-based, case¡Vcontrol study to assess colon cancer risk among individuals with and without HFE gene mutations.

The investigators looked for two major HFE gene mutations, C282Y and H63D. They found that the allele frequencies of the H63D and C282Y mutations were greater among case patients with colon cancer than among cancer-free control subjects. Also, subjects with any HFE gene mutation were more likely to have colon cancer than subjects with no HFE gene mutations, when the analysis was adjusted for other potential risk factors. The risk of colon cancer associated with an HFE gene mutation was independent of a family history of colon cancer.

"If subsequent studies confirm that mutations in the HFE gene are a risk factor for colon cancer, testing for such mutations may allow the identification of a subgroup of individuals that might benefit from intensified colorectal cancer screening," the authors say.

Retinoic Acid Receptor Expression May Be Associated with Increase Lung Cancer Risk

Although the nuclear retinoic acid receptor ß (RARß) has tumor suppressor-like functions in epithelial cells, its expression is associated with poor outcomes for patients with stage I non-small-cell lung cancer (NSCLC). Human telomerase, an enzymatic complex that is activated in immortalized and malignant cells, is also associated with poor prognosis in patients with NSCLC.

In the January 15 issue of the Journal of the National Cancer Institute, Jean-Charles Soria, Reuben Lotan, and colleagues from the University of Texas M. D. Anderson Cancer Center determined whether there was an association between expression of RARß and hTERT, the catalytic subunit of telomerase, in the bronchial epithelium of heavy smokers at risk of developing lung cancer. The authors found a statistically significant correlation between expression of RARß and hTERT. The authors conclude that the association between RARƒÒ and hTERT expression suggests that RARß expression may be indicator of increased risk of lung cancer in heavy smokers.
-end-
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.

Journal of the National Cancer Institute

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