TY - JOUR
T1 - HER-2 gene amplification can be acquired as breast cancer progresses
AU - Meng, Songdong
AU - Tripathy, Debasish
AU - Shete, Sanjay
AU - Ashfaq, Raheela
AU - Haley, Barbara
AU - Perkins, Steve
AU - Beitsch, Peter
AU - Khan, Amanullah
AU - Euhus, David
AU - Osborne, Cynthia
AU - Frenkel, Eugene
AU - Hoover, Susan
AU - Leitch, Marilyn
AU - Clifford, Edward
AU - Vitetta, Ellen
AU - Morrison, Larry
AU - Herlyn, Dorothee
AU - Terstappen, Leon W M M
AU - Fleming, Timothy
AU - Fehm, Tanja
AU - Tucker, Thomas
AU - Lane, Nancy
AU - Wang, Jianqiang
AU - Uhr, Jonathan
PY - 2004/6/22
Y1 - 2004/6/22
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0402993101
DO - 10.1073/pnas.0402993101
M3 - Article
C2 - 15194824
AN - SCOPUS:3042552362
SN - 0027-8424
VL - 101
SP - 9393
EP - 9398
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 25
ER -