Ardavanis Alexandros, Kountourakis Panteleimon, Kyriakou Flora, Malliou Savoula, Mantzaris Ioannis, Garoufali Anastasia, Yiotis Ioulia, Scorilas Andreas, Baziotis Nikolaos, Rigatos Gerasimos
First Department of Medical Oncology, Saint Savas Oncology Hospital, 171 Alexandras Avenue, 115 22 Athens, Hellas.
Oncologist. 2008 Apr;13(4):361-9. doi: 10.1634/theoncologist.2007-0207.
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.
通过对活检材料进行免疫组织化学（IHC）以及荧光或显色原位杂交（FISH/CISH）评估，曲妥珠单抗被认为对人表皮生长因子受体（HER）-2阳性乳腺癌有效。目前，曲妥珠单抗已被批准用于该患者群体的辅助治疗和转移性治疗。由于HER-2细胞外结构域（ECD）水平与转移性疾病的进展相关，我们考虑在血清HER-2 ECD水平较高（≥15 ng/ml）、既往接受过大量治疗且未使用过曲妥珠单抗的复发乳腺癌患者中，采用曲妥珠单抗挽救治疗联合紫杉烷类药物。所有患者此前至少在两种基于蒽环类和紫杉烷类的治疗方案中失败，在进行集中重新分析之前，经IHC和FISH/CISH检测为HER-2阴性，且基线时血清HER-2 ECD呈阳性（≥15 ng/ml）。记录HER-2 ECD的定期血清检测结果，并与反应和生存结果进行比较。最终有22例患者符合挽救治疗条件。5例（23%）患者观察到轻微反应，11例患者病情稳定（SD），临床获益率为73%（22例患者中的16例）。中位疾病进展时间和总生存时间分别为5个月（轻微反应者和病情稳定者为6.5个月）和12个月；11例和8例患者分别在>6个月和>12个月时无疾病进展。治疗开始后12个月和15个月时分别有11例和7例患者存活。此外，总共13例（59.1%）患者获得了生化反应。在我们的研究中，传统上HER-2阴性但HER-2 ECD表达高于正常上限（≥15 ng/ml）的患者，对曲妥珠单抗-紫杉烷联合治疗在生化和临床方面均表现出快速反应。这是第一项根据HER-2 ECD阳性评估HER-2阴性晚期乳腺癌中基于抗HER-2治疗的研究；如果我们的结果得到证实，更多“隐匿性”HER-2阳性乳腺癌患者可能会从抗HER-2治疗中获益。
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