title: Serum HER-2/neu as a prediction and monitoring parameter in a phase II study with weekly paclitaxel in metastatic breast cancer.
abstract: Elevated levels of the extracellular domain of HER-2/neu in serum (sHER-2/neu) have been shown to be of prognostic importance. In this phase II study with weekly paclitaxel in metastatic breast cancer, we investigated the predictive quality of this serum oncoprotein by correlating the outcome of therapy to sHER-2/neu levels. Paclitaxel (90 mg/m2 weekly x6, q9w) was administered to 35 patients with complete outcome assessment and biochemical follow-up. sHER-2/neu was measured using standardized enzyme-linked immunoassays. We found that 62.9% (22/35) of the patients had elevated levels (> or = 15 ng/ml) of sHER-2/neu. The overall response rate (RR) to weekly paclitaxel was 40.0% (14/35). There was no difference in RR between sHER-2/neu-positive patients (40.9%) and sHER-2/neu-negative patients (38.5%; p = 0.4). The progression-free interval was longer for sHER-2/neu-negative patients (53.2 weeks) in comparison to sHER-2/neu-positive patients (31.2 weeks; p = 0.098). Responses were significantly more durable in sHER-2/neu-negative patients (65.2 weeks) than in the sHER-2/neu-positive subgroup (25.7 weeks; p = 0.042). Introducing hypothetical cut-offs into the sHER-2/neu-positive subset, we found that in patients with a sHER-2/neu level of greater than 22 ng/ml, the progression-free survival decreased significantly with increasing sHER-2/neu levels (p < or = 0.022). Considering the high impact of progression-free survival and duration of response as outcome parameters, the sHER-2/neu status is a predictive indicator for benefit from paclitaxel chemotherapy.
authors.affiliation: Medizinische Klinik und Poliklinik II, Schwerpunkt Onkologie und Hämatologie, Universitätsklinikum Charité, Campus Mitte, Humboldt-Universität zu Berlin, 10117 Berlin, Germany. Diana.Lueftner@rz.hu-berlin.de
authors.forename: Diana
authors.initials: D
authors.lastname: Lüftner
authors.forename: Petra
authors.initials: P
authors.lastname: Henschke
authors.forename: Bernd
authors.initials: B
authors.lastname: Flath
authors.forename: Costa
authors.initials: C
authors.lastname: Akrivakis
authors.forename: Sonja
authors.initials: S
authors.lastname: Schnabel
authors.forename: Berit
authors.initials: B
authors.lastname: Prinz
authors.forename: Rita
authors.initials: R
authors.lastname: Geppert
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.forename: Kurt
authors.initials: K
authors.lastname: Possinger
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases