Affiliation:
1. a First Department of Medical Oncology, Saint Savas Oncology Hospital, Athens, Greece
2. b Nuclear Medicine Department, Saint Savas Oncology Hospital, Athens, Greece
3. c Biology Department, University of Athens, Athens, Greece
Abstract
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 (≥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.
Publisher
Oxford University Press (OUP)
Cited by
23 articles.
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