NEW YORK (Reuters Health) - Contrary to common belief, HER-2 gene amplification can be acquired during progression of breast cancer, according to a report in the June 7th PNAS Early Edition.
The 70% to 75% of women with HER-2-negative primary breast tumors will rarely receive anti-Her-2 antibody (trastuzumab) therapy even for recurrent tumors, the authors explain, because amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of the disease.
Dr. Jonathan Uhr from University of Texas Southwestern Medical Center, Dallas and colleagues developed a sensitive blood test to detect circulating tumor cells (CTCs) and compared HER-2 gene status in primary tumors and in corresponding CTCs from 33 women with breast cancer.
In 29 of 33 women, HER-2 gene expression in the primary tumors and in CTCs was concordant, the authors report, and 10 consecutive CTCs were sufficient to determine the HER-2 gene status.
Among 24 women with recurrent breast cancer whose primary tumors were HER-2-negative, 9 developed HER-2 amplification in their CTCs, the report indicates.
HER-2 amplification in the primary tumor was 2.44 times higher than in the corresponding CTCs, the investigators write, suggesting “that the comparatively low ratio of HER-2 gene amplification in CTCs is a consistently reliable surrogate marker for the higher gene amplification of the corresponding tumor.”
Four of the 9 patients were treated with trastuzumab, the results indicate, and one of these patients who presented with advanced disease showed a complete remission lasting more than 1 year. Two additional patients showed partial responses.
“Genetically unstable cancer cells (all types) will continue to change as cancer progresses,” Dr. Uhr told Reuters Health. As the cancer progresses, it may become possible to detect many immunophenotypic and genotypic changes. “This is particularly important at this time as new ‘targeting’ drugs such as trastuzumab become available.”
“The results show that the current dogma is wrong and that patients with HER-2 negative tumors can eventually have metastases that are HER-2 overexpressors,” Dr. Uhr concluded.
“It is necessary to prove that HER-2 gene amplification in CTCs of patients who have acquired HER-2 gene amplification reflect the current tumor burden,” Dr. Uhr said. “This will be approached by performing needle biopsies of metastatic tumor at the time that the blood sample shows acquisition of HER-2 gene amplification.”
Proc Natl Acad Sci USA June 7, 2004 early edition.
MeSH Headings:Breast Neoplasms: Neoplasms: Neoplasms by Site: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
