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Development of circulating tumor cell-endocrine therapy index in patients with hormone receptor-positive breast cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2015 Jun 01; Vol. 21 (11), pp. 2487-98. Date of Electronic Publication: 2014 Nov 07. - Publication Year :
- 2015
-
Abstract
- Background: Endocrine therapy (ET) fails to induce a response in one half of patients with hormone receptor (HR)-positive metastatic breast cancer (MBC), and almost all will eventually become refractory to ET. Circulating tumor cells (CTC) are associated with worse prognosis in patients with MBC, but enumeration alone is insufficient to predict the absolute odds of benefit from any therapy, including ET. We developed a multiparameter CTC-Endocrine Therapy Index (CTC-ETI), which we hypothesize may predict resistance to ET in patients with HR-positive MBC.<br />Methods: The CTC-ETI combines enumeration and CTC expression of four markers: estrogen receptor (ER), B-cell lymphoma 2 (BCL-2), Human Epidermal Growth Factor Receptor 2 (HER2), and Ki67. The CellSearch System and reagents were used to capture CTC and measure protein expression by immunofluorescent staining on CTC.<br />Results: The feasibility of determining CTC-ETI was initially established in vitro and then in a prospective single-institution pilot study in patients with MBC. CTC-ETI was successfully determined in 44 of 50 (88%) patients. Eighteen (41%), 9 (20%), and 17 (39%) patients had low, intermediate, and high CTC-ETI scores, respectively. Interobserver concordance of CTC-ETI determination was from 94% to 95% (Kappa statistic, 0.90-0.91). Inter- and cell-to-cell intrapatient heterogeneity of expression of each of the CTC markers was observed. CTC biomarker expression was discordant from both primary and metastatic tissues.<br />Conclusions: CTC expression of ER, BCL-2, HER2, and Ki67 can be reproducibly measured with high analytical validity using the CellSearch System. The clinical implications of CTC-ETI, and of the heterogeneity of CTC biomarker expression, are being evaluated in an ongoing prospective trial.<br /> (©2014 American Association for Cancer Research.)
- Subjects :
- Biomarkers, Tumor blood
Biomarkers, Tumor genetics
Breast Neoplasms blood
Breast Neoplasms pathology
Female
Gene Expression Regulation, Neoplastic
Humans
Ki-67 Antigen blood
MCF-7 Cells
Neoplasm Metastasis
Prognosis
Proto-Oncogene Proteins c-bcl-2 blood
Receptor, ErbB-2 blood
Receptors, Estrogen blood
Breast Neoplasms genetics
Ki-67 Antigen genetics
Neoplastic Cells, Circulating pathology
Proto-Oncogene Proteins c-bcl-2 genetics
Receptor, ErbB-2 genetics
Receptors, Estrogen genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 21
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 25381338
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-14-1913