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.
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

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.