[HER-2 gene amplification can be acquired as breast cancer progresses]
>>Published online before print June 11, 2004
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0402993101
Medical Sciences
HER-2 gene amplification can be acquired as breast cancer progresses
Songdong Meng a, Debasish Tripathy b, Sanjay Shete c, Raheela Ashfaq d, Barbara Haley b, Steve Perkins e, Peter Beitsch f, Amanullah Khan g, David Euhus h, Cynthia Osborne b, Eugene Frenkel b, Susan Hoover h, Marilyn Leitch h, Edward Clifford i, Ellen Vitetta a, Larry Morrison j, Dorothee Herlyn k, Leon W. M. M. Terstappen l, Timothy Fleming m, Tanja Fehm n, Thomas Tucker a, Nancy Lane a, Jianqiang Wang a, and Jonathan Uhr a,o,p
aCancer Immunobiology Center, bDepartment of Medicine, Komen Breast Cancer Center, dDepartment of Pathology, fDallas Surgical Group, hCenter for Breast Care, and iDepartment of Surgery, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390; cDepartment of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; eSt. Paul University Hospital, Dallas, TX 75235; gCancer Center Associates, Dallas, TX 75235; jVysis, Inc., Downers Grove, IL 60515; kWistar Institute, Philadelphia, PA 19104; lImmunicon Corp., Huntingdon, PA 19006; mDepartment of Surgery, Washington University School of Medicine, St. Louis, MO 63130; and nDepartment of Gynecology and Obstetrics, University of Tubingen, 72076 Tubingen, Germany
Contributed by Jonathan Uhr, April 28, 2004
Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 ± 2.72 vs. 2.8 ± 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.
oJ.U. holds stock in Immunicon Corp.<<
Clearly involves the CellSearch kit.
Cheers, Tuck |
