Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial.
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 (n = 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, P < 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, P = 0.045) and a decrease of sHER2 levels during NT (P = 0.02), which was also significant in multivariate analysis (OR = 3.29, 95% CI 1.001-10.89, P = 0.049). In HER2-negative patients, we observed no association between sHER2 levels and pCR (P > 0.05). Monitoring sHER2 levels in the presence of anti-HER2 treatment might be an adjunct to the clinical evaluation during NT.
Witzel
Isabell
I
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Loibl
Sibylle
S
von Minckwitz
Gunter
G
Mundhenke
Christoph
C
Huober
Jens
J
Hanusch
Claus
C
Henschen
Stephan
S
Hauschild
Maik
M
Lantzsch
Tilmann
T
Tesch
Hans
H
Latos
Kunibert
K
Just
Marianne
M
Hilfrich
Jörn
J
Barinoff
Jana
J
Eulenburg
Christine Zu
CZ
Roller
Marc
M
Untch
Michael
M
Müller
Volkmar
V
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005858:Germany; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016017:Odds Ratio; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000097:blood*; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human