HER-2 gene amplification can be acquired as breast cancer progresses

Songdong Meng, Debasish Tripathy, Sanjay Shete, Raheela Ashfaq, Barbara Haley, Steve Perkins, Peter Beitsch, Amanullah Khan, David Euhus, Cynthia Osborne, Eugene Frenkel, Susan Hoover, Marilyn Leitch, Edward Clifford, Ellen Vitetta, Larry Morrison, Dorothee Herlyn, Leon W M M Terstappen, Timothy Fleming, Tanja FehmThomas Tucker, Nancy Lane, Jianqiang Wang, Jonathan Uhr

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419 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9393-9398
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number25
DOIs
StatePublished - Jun 22 2004

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    Meng, S., Tripathy, D., Shete, S., Ashfaq, R., Haley, B., Perkins, S., Beitsch, P., Khan, A., Euhus, D., Osborne, C., Frenkel, E., Hoover, S., Leitch, M., Clifford, E., Vitetta, E., Morrison, L., Herlyn, D., Terstappen, L. W. M. M., Fleming, T., ... Uhr, J. (2004). HER-2 gene amplification can be acquired as breast cancer progresses. Proceedings of the National Academy of Sciences of the United States of America, 101(25), 9393-9398. https://doi.org/10.1073/pnas.0402993101