HER-2 gene amplification can be acquired as breast cancer progresses.
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.
Meng
Songdong
S
Cancer Immunobiology Center, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Tripathy
Debasish
D
Shete
Sanjay
S
Ashfaq
Raheela
R
Haley
Barbara
B
Perkins
Steve
S
Beitsch
Peter
P
Khan
Amanullah
A
Euhus
David
D
Osborne
Cynthia
C
Frenkel
Eugene
E
Hoover
Susan
S
Leitch
Marilyn
M
Clifford
Edward
E
Vitetta
Ellen
E
Morrison
Larry
L
Herlyn
Dorothee
D
Terstappen
Leon W M M
LW
Fleming
Timothy
T
Fehm
Tanja
T
Tucker
Thomas
T
Lane
Nancy
N
Wang
Jianqiang
J
Uhr
Jonathan
J
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068878:Trastuzumab