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

Publication

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

Journal Paper/Review - Nov 1, 2017

De Gregorio Amelie, Janni Wolfgang, Fasching Peter A, Taran Florin-Andrei, Hartkopf Andreas, Jaeger Bernadette, Meier-Stiegen Franziska, Pantel Klaus, Schneeweiss Andreas, Mueller Volkmar, Riethdorf Sabine, Alunni-Fabbroni Marianna, Trapp Elisabeth, Rack Brigitte, De Gregorio Nikolaus, Scholz Christoph, Huober Jens, Friedl Thomas W P, Fehm Tanja

Citation

De Gregorio A, Janni W, Fasching P, Taran F, Hartkopf A, Jaeger B, Meier-Stiegen F, Pantel K, Schneeweiss A, Mueller V, Riethdorf S, Alunni-Fabbroni M, Trapp E, Rack B, De Gregorio N, Scholz C, Huober J, Friedl T, Fehm T. 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; 1:1-12.

Type

Journal Paper/Review (English)

Journal

JCO Precis Oncol 2017; 1

Publication Date

Nov 1, 2017

Issn Electronic

2473-4284

Pages

1-12

Brief description/objective

PURPOSE
Discordance in human epidermal growth factor receptor 2 (HER2) status between primary tumor and metastases might have important implications for treatment response and therapy decisions. Here, we evaluate both the frequency of circulating tumor cells (CTCs) and the factors predicting HER2 discordance between primary tumor and CTCs as a potential surrogate for tumor biology and tumor heterogeneity in patients with metastatic breast cancer.

PATIENTS AND METHODS
The number of CTCs in 7.5 mL of peripheral blood and HER2 status were evaluated in 1,123 women with HER2-negative metastatic breast cancer. HER2 discordance was defined as the presence of at least one CTC with a strong immunocytochemical HER2 staining intensity. Factors predicting discordance in HER2 phenotype were assessed using multivariable logistic regression.

RESULTS
Overall, 711 (63.3%) of 1,123 screened patients were positive for CTCs (≥ one CTC). Discordance in HER2 phenotype between primary tumor and CTCs was observed in 134 patients (18.8%) and was significantly associated with histologic type (lobular ductal; odds ratio [OR], 2.67; 95% CI, 1.63 to 4.39; < .001), hormone receptor status (positive negative; OR, 2.84; 95% CI, 1.15 to 7.02; = .024), and CTC number (≥ five one to four; OR, 7.64; 95% CI, 3.97 to 14.72; < .001).

CONCLUSION
HER2 discordance between primary tumor and CTCs was observed in 18.8% of patients and was associated with histologic type, hormone receptor status of the primary tumor, and CTC number. The clinical utility of CTCs as liquid biopsy to assess tumor heterogeneity of metastatic disease and guide treatment decisions must be evaluated in prospective randomized trials.