Nearly 1 in 5 patients with metastatic breast cancer with measurable circulating tumor cells (CTCs) have discordant HER2 status between their primary tumor and CTCs, according to a study published in JCO Precision Oncology.1

CTCs have prognostic relevance in metastatic breast cancer, though it is unknown the degree to which these cells and their corresponding primary tumors are phenotypically heterogeneous. For this study, which was part of the DETECT study ( Identifier: NCT01619111), researchers analyzed liquid biopsies from patients with HER2-negative metastatic breast cancer to determine any discordance in HER2 status between circulating cells and primary tumors.

Among the 1123 screened patients, the median age was 62, 65.4% were postmenopausal, more than 70% had stage pT1 or pT2 disease, and 78.9% were hormone receptor­–positive. At least 1 CTC was detected in 63.3% of patients.

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Among the 711 patients with at least 1 detected CTC, 18.8% had HER2-positive circulating cells, contrasting with a HER2-negative primary tumor. Patients with lobular carcinoma were more than twice as likely to have HER2-positive CTCs as patients with ductal carcinoma (odds radio [OR], 2.67), as were patients with hormone receptor–positive vs –negative disease (OR, 2.84).

Patients with at least 5 detected CTCs were over 7 times as likely to have HER2-positive circulating cells as those with fewer (OR, 7.64).

The researchers did not, however, note whether treatment plan might affect the observed HER2-status discordance.

The authors concluded that “knowledge of factors associated with discordance in HER2 status may be incorporated into today’s clinical practice by guiding the decision process for performing biopsy to characterize metastatic relapse.”


  1. De Gregorio A, Friedl TW, Huober J, et al. Discordance in human epidermal growth factor receptor 2 (HER2) phenotype between primary tumor and circulating tumor cells in women with HER2-negative metastatic breast cancer. JCO Precis Oncol. 2017 Sep 28. doi: 10.1200/PO.17.00023 [Epub ahead of print]