Τίτλος:
Trastuzumab plus paclitaxel or docetaxel in HER-2-negative/HER-2 ECD-positive anthracycline- and taxane-refractory advanced breast cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 (≥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 (≥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 (≥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. ©AlphaMed Press.
Συγγραφείς:
Ardavanis, A.
Kountourakis, P.
Kyriakou, F.
Malliou, S.
Mantzaris, I.
Garoufali, A.
Yiotis, I.
Scorilas, A.
Baziotis, N.
Rigatos, G.
Περιοδικό:
The oncologist
Λέξεις-κλειδιά:
anthracycline; antiemetic agent; capecitabine; docetaxel; gemcitabine; navelbine; paclitaxel; taxane derivative; trastuzumab, adult; aged; alopecia; anemia; article; blood sampling; breast cancer; cancer growth; constipation; diarrhea; female; fluorescence in situ hybridization; human; human tissue; immunohistochemistry; leukopenia; major clinical study; multiple cycle treatment; nausea and vomiting; neutropenia; oncogene neu; overall survival; phlebitis; priority journal; prophylaxis; refractory period; salvage therapy; thrombocytopenia; treatment response, Adult; Aged; Anthracyclines; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carrier Proteins; Disease Progression; Drug Resistance, Neoplasm; Female; Genes, erbB-2; Humans; Middle Aged; Paclitaxel; Survival Analysis; Taxoids; Treatment Failure; Treatment Outcome; Tumor Markers, Biological
DOI:
10.1634/theoncologist.2007-0207
