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.

  • 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
    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

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