Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial

Isabell Witzel (1) , Sibylle Loibl (2) , Gunter Minckwitz (2) , Christoph Mundhenke (3) , Jens Huober (4) , Claus Hanusch (5) , Stephan Henschen (6) , Maik Hauschild (7) , Tilmann Lantzsch (8) , Hans Tesch (9) , Kunibert Latos (10) , Marianne Just (11) , Jörn Hilfrich (12) , Jana Barinoff (13) , Christine Zu Eulenburg (14) , Marc Roller (2) , Michael Untch (15) , Volkmar Müller (1)

1 Department of Gynecology
2 German Breast Group, Forschungs GmbH
3 Department of Gynecology and Obstetrics
4 Department of Gynecology
5 Department of Gynecology and Obstetrics
6 Johanniter-Krankenhaus, Genthin-Stendal
7 Frauenklinik Rheinfelden Betriebs GmbH
8 Krankenhaus St. Elisabeth und St. Barbara
9 Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus
10 Katharinen-Hospital
11 Onkologische Schwerpunktpraxis
12 Frauenklinik der Henriettenstiftung Hannover
13 Deptartment of Gynecology & Gynecologic Oncology
14 Department of Medical Biometry and Epidemiology
15 Department of Gynecology and Obstetrics

In the context of neoadjuvant therapy (NT) for breast cancer patients, different targeted therapy approaches are currently evaluated in clinical trials. Serum markers could help to monitor and optimize such treatment strategies. We investigated human epidermal growth factor receptor 2 serum (sHER2) levels in 175 breast cancer patients participating in the GeparQuattro trial. This study incorporated NT approaches and additional trastuzumab treatment for all patients with HER2-positive tumors. Human epidermal growth factor receptor 2 serum levels were measured by enzyme-linked immunosorbent assay (ELISA) before initiation of NT and after NT (pre-surgery) in a HER2-positive ( = 90) and a HER2-negative patient cohort (n = 85). Median pre-chemotherapy sHER2 levels were higher in patients with positive HER2 status of the primary tumor than in patients with negative HER2 status (14.9 ng/ml vs. 7.7 ng/ml,  < 0.001). A pre-chemotherapy sHER2 cut-off level of 10 ng/ml had the best sensitivity and specificity in discriminating between HER2-positive and HER2-negative primary tumors. In HER2-positive patients, we found a significant positive association between pathological complete remission (pCR) and elevated sHER2 levels (above 15 ng/ml,  = 0.045) and a decrease of sHER2 levels during NT ( = 0.02), which was also significant in multivariate analysis (OR = 3.29, 95% CI 1.001–10.89,  = 0.049). In HER2-negative patients, we observed no association between sHER2 levels and pCR ( > 0.05). Monitoring sHER2 levels in the presence of anti-HER2 treatment might be an adjunct to the clinical evaluation during NT.

Mots clés: Breast cancer; Neoadjuvant therapy; HER2; Serum

Isabell Witzel, Sibylle Loibl, Gunter Minckwitz, Christoph Mundhenke, Jens Huober, et al.. Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial. Breast Cancer Research and Treatment, 2010, 123 (2), pp.437-445. ⟨10.1007/s10549-010-1030-9⟩. ⟨hal-00553821⟩