HER2 status differed between primary tumor and CTCs in 18.8% of women with MBC


Discordance in HER2 status between the primary breast tumor and circulating tumor cells (CTCs) in women with HER2-negative metastatic disease was 18.8% in a prospective cohort of patients.

The probability of discordance decreased with increasing age but increased with primary tumors that were hormone-receptor positive, higher grade, and of lobular histology, Amelie De Gregorio, MD, and associates reported in JCO Precision Oncology.

The investigators evaluated the HER2 status of CTCs obtained from women with HER2-negative breast cancer screened in the ongoing German DETECT III trial , which is aimed at determining the efficacy of lapatinib in patients with initially HER2-negative metastatic breast cancer but HER2-positive CTCs. HER2 discordance was defined as the presence of a single CTC or more within 7.5 mL of peripheral blood that showed a strong immunohistochemical (IHC) staining intensity (IHC score 3+).

Out of 1,123 women screened, at least one CTC was detected in blood samples from 711 women (63.3%; 95% confidence interval, 60.4%-66.1%). The median number of CTCs detected was seven (interquartile range, 2-30; range, 1-35,078 CTCs), and discordance in HER2 phenotype between primary tumor and CTCs was found in 134 patients (18.8%), Dr. De Gregorio of University Hospital Ulm (Germany) and associates reported (JCO Precis Oncol. 2017 Sep 28. doi: 10.1200/PO.17.00023 ).

In a multivariable analysis, histologic type (lobular vs. ductal; odds ratio, 2.67; P less than .001), hormone receptor status (positive vs. negative; OR, 2.84; P = .024), and CTC number (greater than 5 vs. 1-4 CTCs; OR, 7.64; P less than .001) significantly and independently predicted discordance in HER2 phenotype between primary tumor and CTCs. There was also a significant effect of age, with the probability of discordance decreasing with increasing age, the investigators noted.

“The 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,” the investigators wrote.

“Moreover, the concept of liquid biopsy using CTCs as a real-time noninvasive monitoring tool to evaluate tumor biology, progression, and heterogeneity as a basis for more personalized treatment decisions should be tested in prospective randomized clinical trials,” they added.

The DETECT study program is supported by the Investigator-Initiated Study Program of Janssen Diagnostics, with clinical trials also supported by Pierre Fabre Pharma, TEVA Pharmaceuticals Industries, Amgen, Novartis Pharma, and Eisai. Dr. De Gregorio disclosed an advisory role with Roche Pharma AG; several coauthors disclosed consultancy and funding from various pharmaceutical companies.


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