title: Trastuzumab plus paclitaxel or docetaxel in HER-2-negative/HER-2 ECD-positive anthracycline- and taxane-refractory advanced breast cancer.
abstract: Trastuzumab is considered effective against human epidermal growth factor receptor (HER)-2-positive breast cancer as assessed by immunohistochemistry (IHC) and fluorescence or chromogenic in situ hybridization (FISH/CISH) on biopsy material. Trastuzumab is now approved in both the adjuvant and metastatic settings for this patient population. Because HER-2 extracellular domain (ECD) levels have been correlated with disease progression in the metastatic setting, we considered trastuzumab salvage therapy plus a taxane in heavily pretreated trastuzumab-naive relapsed breast cancer patients with high serum levels of HER-2 ECD (> or =15 ng/ml). All patients had previously failed at least two lines of anthracycline- and taxane-based regimens and were HER-2 negative by IHC and FISH/CISH prior to a centralized reanalysis, and were serum positive for HER-2 ECD (> or =15 ng/ml) at baseline. Regular serum accounts of HER-2 ECD were recorded and compared with response and survival outcomes. Twenty-two patients were finally eligible for salvage therapy. Minor responses were observed in five (23%) and stable disease (SD) was observed in 11 patients, leading to a clinical benefit rate of 73% (16 of 22 patients). The median time to progression and overall survival time were 5 (6.5 months in minor responders and SD) and 12 months, respectively; 11 and eight patients remained progression free for >6 and >12 months, respectively. Eleven and seven patients were alive at 12 and 15 months, respectively, after treatment start. Furthermore, in total, 13 (59.1%) patients obtained a biochemical response. In our study, patients with conventionally HER-2-negative disease but with expression of HER-2 ECD above the normal limit (> or =15 ng/ml) displayed a rapid response, both biochemically and clinically, to the trastuzumab-taxane combination. This is the first study assessing anti-HER-2-based treatment in HER-2-negative advanced breast cancer according to HER-2 ECD positivity; if our results are confirmed, additional patients with "hidden" HER-2-positive breast cancer might benefit from anti-HER-2 treatment.
authors.affiliation: First Department of Medical Oncology, Saint Savas Oncology Hospital, 171 Alexandras Avenue, 115 22 Athens, Hellas. ardavanis@yahoo.com
authors.forename: Alexandros
authors.initials: A
authors.lastname: Ardavanis
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Kountourakis
authors.forename: Flora
authors.initials: F
authors.lastname: Kyriakou
authors.forename: Savoula
authors.initials: S
authors.lastname: Malliou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mantzaris
authors.forename: Anastasia
authors.initials: A
authors.lastname: Garoufali
authors.forename: Ioulia
authors.initials: I
authors.lastname: Yiotis
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Baziotis
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Rigatos
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D002352:Carrier Proteins / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D018734:Genes, erbB-2 / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C513410:ECD protein, human; D043823:Taxoids; D000077143:Docetaxel; D000068878:Trastuzumab; D017239:Paclitaxel