Other highlights in the September 7 JNCI

September 06, 2005

Status of Progesterone Receptor May Be Important Factor in Breast Cancer

Knowing the status of the progesterone receptor (PR) in women with estrogen receptor (ER)-positive breast tumors may have important clinical relevance, including how these tumors respond to tamoxifen, according to a new study.

Many breast cancer therapies have been developed for women whose tumors overexpress ER (i.e., ER-positive tumors). However, data suggest that tumors that are ER-positive but PR-negative are less sensitive to tamoxifen compared with those that are ER- and PR-positive.

To determine whether breast tumors that are ER-positive and PR-negative are more likely to be aggressive than ER-positive/PR-positive tumors, Richard M. Elledge, M.D., of the Baylor College of Medicine in Houston, and colleagues conducted a retrospective clinical analysis of more than 44,000 breast cancer patients with ER-positive tumors. They compared clinical and biologic features of the tumors based on PR status. In addition, the researchers examined HER-1 and HER-2 status in a subset of more than 1,700 patients.

The authors found that the ER-positive/PR-negative tumors--which were larger, divided more rapidly and were more likely to have an abnormal number of chromosomes than the ER- and PR-positive tumors--also more often expressed HER-1 and overexpressed HER-2. Recurrence was higher among tamoxifen-treated women with ER-positive/PR-negative tumors that expressed HER-1 or HER-2 but not among women with ER- and PR-positive tumors that expressed these growth factor receptors. The authors conclude that the lack of PR expression in ER-positive tumors may be a marker of aberrant growth factor signaling that could contribute to tamoxifen resistance.

In an editorial, Cindy A. Wilson, Ph.D., and Dennis J. Slamon, M.D., Ph.D., of the David Geffen School of Medicine at the University of California Los Angeles, discuss how these findings support new hypotheses regarding ER activity in PR-negative breast cancer. "These data could have a profound translational clinical impact on directing therapeutic interventions for patients who have ER-positive tumors but who display a steroid hormone-resistant or -independent phenotype," they write.

Contact:
  • Article: Kimberlee Barbour, Baylor College of Medicine, 713-798-4712, kbarbour@bcm.edu
  • Editorial: Kim Irwin, University of California Los Angeles, 310-206-2805, kirwin@mednet.ucla.edu

    Hirschsprung Disease Gene May Also Be Involved in Some Melanomas

    A new study has found that mutations in a gene involved in Hirschsprung disease--a rare disease of the colon that usually occurs in children--may also predispose carriers to malignant melanoma.

    Because the endothelin signaling pathway plays an important role in the differentiation and migration of melanocytes, the cells from which melanomas arise, Nadem Soufir, M.D., Ph.D., of the Hopital Bichat-Claude Bernard in Paris, and colleagues investigated whether mutations in the gene endothelin receptor B (EDNRB), which is involved in Hirschsprung disease, could also predispose individuals to malignant melanoma. They sequenced the gene in 137 patients with malignant melanoma and 130 matched control subjects.

    EDNRB mutations were identified in four control subjects and in 15 patients, 14 of whom carried mutations reported in Hirschsprung disease and/or resulted in loss of gene function. The authors found a direct association between melanoma risk and the presence of EDNRB mutations. They conclude that their data strongly suggest that EDNRB is involved in the predisposition of two different multigenic disorders, Hirschsprung disease and melanoma.

    Contact: Nadem Soufir, Hopital Bichat-Claude Bernard, nadem.soufir@bch.ap-hop-paris.fr

    Treatment Shows Activity Against Aerodigestive Tract Cancer Cells

    A new study has found that the farnesyltransferase inhibitor SCH66336, which inhibits the growth of non-small-cell lung cancer (NSCLC), appears to inhibit the angiogenic activities of NSCLC and head and neck squamous cell carcinoma (HNSCC) cells.

    Despite therapeutic advances, the outcomes for people diagnosed with aerodigestive tract cancers such as NSCLC and HNSCC remain poor, and most patients with these cancers die from metastatic disease. SCH66336, in combination with other receptor tyrosine kinase inhibitors, has been shown to inhibit the growth of NSCLC cells.

    Ho-Young Lee, Ph.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues investigated whether SCH66336 also inhibits angiogenesis of aerodigestive tract cancer cells. They found that SCH66336 appears to inhibit angiogenic activity of NSCLC and HNSCC cells by inhibiting the interaction between hypoxia-inducible factor 1 alpha and heat shock protein 90 and thus decreasing hypoxia-inducible factor 1 alpha expression. The authors conclude that their results provide a new rationale for the use of farnesyltransferase inhibitors as inhibitors of tumor angiogenesis in aerodigestive cancer.

    Contact: Laura Sussman, Communications Office, M. D. Anderson Cancer Center, 713-745-2457, lsussman@mdanderson.org

    Overexpression of Gene That Interacts With Brca2 May Play Role in Genesis of Breast Cancer

    Overexpression of the gene EMSY may play a role in the development of sporadic breast cancers, according to a new study.

    The protein encoded by the EMSY gene interacts with the Brca2 protein, whose gene has been linked to familial breast cancer. Mutations in BRCA2 are not found in sporadic breast cancers, but the EMSY gene is amplified in 13% of these cancers. It has been suggested that overexpression of the EMSY gene may be an alternate mechanism for suppression of the activity of the Brca2 protein, which could lead to the development of malignant breast cells.

    Connie J. Eaves, Ph.D., and David Huntsman, M.D., of the British Columbia Cancer Agency in Vancouver, and colleagues conducted a series of experiments in a human breast cell line to determine whether overexpression of the EMSY gene would mimic the chromosome instability found in breast cancer cells that have lost functional Brca2 protein. They found that ESMY overexpression induced a chromosome instability phenotype that was similar to that found in BRCA2-deficient cells and conclude that EMSY overexpression may play a role in the genesis of breast cancer.

    Contact: Nicole Adams, BC Cancer Agency, 604-877-6272, nadams@bccancer.bc.ca

    Phase I Study Finds New Drug Well Tolerated in Patients With Prostate Cancer

    A phase I study, conducted by Kim N. Chi, M.D., of the Vancouver Cancer Centre, and colleagues, has found that OGX-011, an antisense oligonucleotide to clusterin, is well tolerated and reduces expression of clusterin--a protein that promotes cell survival--in prostate tumors.

    Contact: Papinder Rehncy, BC Cancer Agency, 604-877-6261, prehncy@bccancer.bc.ca

    Also in the September 7 JNCI:
  • Recent Improvements in Prostate Cancer Outcomes May Be Result of Shift in Classification: http://www.eurekalert.org/emb_releases/2005-09/jotn-rii083105.php
  • Letrozole Following Tamoxifen May Benefit Women With Breast Cancer: http://www.eurekalert.org/emb_releases/2005-09/jotn-lft083105.php
    -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. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

    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.