title: Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial.
abstract: 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.
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Witzel
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Christoph
authors.initials: C
authors.lastname: Mundhenke
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Claus
authors.initials: C
authors.lastname: Hanusch
authors.forename: Stephan
authors.initials: S
authors.lastname: Henschen
authors.forename: Maik
authors.initials: M
authors.lastname: Hauschild
authors.forename: Tilmann
authors.initials: T
authors.lastname: Lantzsch
authors.forename: Hans
authors.initials: H
authors.lastname: Tesch
authors.forename: Kunibert
authors.initials: K
authors.lastname: Latos
authors.forename: Marianne
authors.initials: M
authors.lastname: Just
authors.forename: Jörn
authors.initials: J
authors.lastname: Hilfrich
authors.forename: Jana
authors.initials: J
authors.lastname: Barinoff
authors.forename: Christine Zu
authors.initials: CZ
authors.lastname: Eulenburg
authors.forename: Marc
authors.initials: M
authors.lastname: Roller
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
mesh_terms: 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
chemical_list: 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