Abstract
BackgroundIn metastatic breast cancer (MBC), antigen profiles of metastatic tissue and primary tumor differ in up to 20 % of patients. Reassessment of predictive markers, including human epidermal growth factor receptor 2 (HER2) expression, might help to optimize MBC treatment. While tissue sampling is invasive and often difficult to repeat, circulating tumor cell (CTC) analysis requires only a blood sample and might provide an easy-to-repeat, real-time “liquid biopsy” approach. The present retrospective study was conducted to compare HER2 expression in primary tumors, metastatic tissue, and circulating tumor cells (CTCs) from MBC patients and to analyze the potential impact of HER2 overexpression by CTCs on progression-free (PFS) and overall survival (OS) in MBC.MethodsCTC-positive (five or more CTCs/7.5 mL blood; CellSearch®, Janssen Diagnostics) MBC patients starting a new line of systemic treatment were eligible for the study. HER2 status of CTCs was determined by immunofluorescence (CellSearch®). HER2 status of primary (PRIM) and metastatic (MET) tumor tissue was determined by immunohistochemistry. Data were analyzed using descriptive statistics and Kaplan–Meier plots.ResultsOne hundred seven patients (median age (range) 57 (33–81) years) were included. 100/107 (93 %) patients were followed-up for a median [95 % confidence interval (CI)] of 28.5 [25.1–40.1] months. Of 37/107 (35 %) CTC-HER2-positive patients only 10 (27 %) were PRIM-HER2-positive. 6/46 (13 %) patients were MET-HER2-positive; only 2/10 (20 %) CTC-HER2-positive patients were MET-HER2-positive. Overall accuracy between CTC-HER2 expression and PRIM-HER2 and MET-HER2 status was 69 % and 74 %, respectively. Kaplan–Meier plots of PFS and OS by CTC-HER2 status revealed significantly longer median [95 % CI] PFS of CTC-HER2-positive versus CTC-HER2-negative patients (7.4 [4.7–13.7] versus 4.34 [3.5–5.9] months; p = 0.035). CTC-HER2-positive status showed no significant difference for OS (13.7 [7.7–30.0] versus 8.7 [5.9–15.3] months; p = 0.287).ConclusionsHER2 status can change during the course of breast cancer. CTC phenotyping may serve as an easy-to-perform “liquid biopsy” to reevaluate HER2 status and potentially guide treatment decisions. Further, prospective studies are needed.
Highlights
In metastatic breast cancer (MBC), antigen profiles of metastatic tissue and primary tumor differ in up to 20 % of patients
The primary tumor was estrogen receptor (ER)-positive in 78 (73 %) patients, progesterone receptor (PR)-positive in 68 (64 %) patients, and human epidermal growth factor receptor 2 (HER2)-negative in 91 (85 %) patients. 80 % of all patients had multiple metastatic sites, 18 % had bone metastases, 21 % had visceral or local metastases, and 62 % had both. 48 % of all patients received firstline treatment for MBC, 21 % second-line treatment, and 31 % third- or further-line treatment. 13 % of patients were pretreated with HER2-targeted therapy before study entry
HER2 status of circulating tumor cell (CTC), primary tumor, and metastases The median number of CTCs detected per 7.5 mL blood was 27 (5–5000)
Summary
In metastatic breast cancer (MBC), antigen profiles of metastatic tissue and primary tumor differ in up to 20 % of patients. As MBC treatment evolves towards targeted therapy, the efficacy of novel therapies is increasingly based on the biological characteristics of the disease. These are currently determined using primary tumor tissue (e.g. HER2-status) or by means of sequential metastatic tissue biopsies because breast cancer phenotype may change during disease progression [1, 2]. Markers to predict the efficacy of MBC treatment frequently relate to the characteristics of the primary tumor, even though antigen profiles of the primary tumor and the distant metastases have been reported to differ in 7–20 % of patients [3,4,5,6,7]. Due to the invasive nature of MBC, tissue sampling of metastatic sites may be difficult to perform, especially if repeated sampling is required [10]
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