Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program

Publication

Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program

Journal Paper/Review - Nov 25, 2021

Müller V, Müller L, Janni W, Wimberger P, Jäger B, Pantel K, Riethdorf S, Harbeck N, Fehm T, Hoffmann O, Rübner M, Huober Jens, Banys-Paluchowski M, Friedl T W P, Fasching P A, Schneeweiss A, Hartkopf A, Wallwiener D, Rack B, Meier-Stiegen F, DETECT study group

Citation

Müller V, Müller L, Janni W, Wimberger P, Jäger B, Pantel K, Riethdorf S, Harbeck N, Fehm T, Hoffmann O, Rübner M, Huober J, Banys-Paluchowski M, Friedl T, Fasching P, Schneeweiss A, Hartkopf A, Wallwiener D, Rack B, Meier-Stiegen F, DETECT study group. Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program. ESMO Open 2021; 6:100299.

Type

Journal Paper/Review (English)

Journal

ESMO Open 2021; 6

Publication Date

Nov 25, 2021

Issn Electronic

2059-7029

Pages

100299

Brief description/objective

BACKGROUND
Circulating tumor cells (CTCs) have been reported to predict clinical outcome in metastatic breast cancer (MBC). Biology of CTCs may differ from that of the primary tumor and HER2-positive CTCs are found in some patients with HER2-negative tumors.

PATIENTS AND METHODS
Patients with HER2-negative MBC were screened for participation in DETECT III and IV trials before the initiation of a new line of therapy. Blood samples were analyzed using CELLSEARCH. CTCs were labeled with an anti-HER2 antibody and classified according to staining intensity (negative, weak, moderate, or strong staining).

RESULTS
Screening blood samples were analyzed in 1933 patients with HER2-negative MBC. As many as 1217 out of the 1933 screened patients (63.0%) had ≥1 CTC per 7.5 ml blood; ≥5 CTCs were detected in 735 patients (38.0%; range 1-35 078 CTCs, median 8 CTCs). HER2 status of CTCs was assessed in 1159 CTC-positive patients; ≥1 CTC with strong HER2 staining was found in 174 (15.0%) patients. The proportion of CTCs with strong HER2 staining among all CTCs of an individual patient ranged between 0.06% and 100% (mean 15.8%). Patients with estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were more likely to harbor ≥1 CTC with strong HER2 staining. CTC status was significantly associated with overall survival (OS). Detection of ≥1 CTC with strong HER2 staining was associated with shorter OS [9.7 (7.1-12.3) versus 16.5 (14.9-18.1) months in patients with CTCs with negative-to-moderate HER2 staining only, P = 0.013]. In multivariate analysis, age, ER status, PR status, Eastern Cooperative Oncology Group performance status, therapy line, and CTC status independently predicted OS.

CONCLUSION
CTC detection in patients with HER2-negative disease is a strong prognostic factor. Presence of ≥1 CTC with strong HER2 staining was associated with shorter OS, supporting a biological role of HER2 expression on CTCs.