对于HER2阳性晚期乳腺癌患者，曲妥珠单抗治疗可能许多年保持肿瘤完全缓解。那么如果影像学检查（例如造影剂增强CT、造影剂增强MRI、18F-FDG-PET-CT或同位素骨扫描）保持完全缓解，能否停用曲妥珠单抗？
2019年9月6日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表荷兰阿姆斯特丹癌症研究所、多德勒克阿尔伯特施魏策尔医院、鹿特丹大学医疗中心癌症研究所、代尔夫特雷尼尔德格拉夫医院、布雷达安非亚医院、乌得勒支圣安东尼厄斯医院、鹿特丹伊卡齐亚医院、海牙哈加医院的研究报告，分析了HER2阳性晚期乳腺癌患者影像学完全缓解与总生存的相关临床特征、影像学完全缓解病例停用曲妥珠单抗的影响。
该多中心回顾分析对2000年1月～2014年12月荷兰八家医院717例曲妥珠单抗一线或二线治疗HER2阳性晚期乳腺癌患者的医疗记录数据进行回顾分析。通过多因素比例风险回归模型，确定影像学完全缓解与总生存的独立预后因素。对影像学完全缓解后维持或停用曲妥珠单抗患者的进展时间和乳腺癌相关生存也进行了评估。
结果，患者诊断时中位年龄53岁，中位随访109个月（四分位：72～148）期间，影像学完全缓解患者72例（10%）。
总生存的最强相关因素为影像学完全缓解，对其他影响因素进行校正后，影像学完全缓解与否相比：
总生存比例：52%比7%
总死亡风险：低73%（校正风险比：0.27，95%置信区间：0.18～0.40）
影像学完全缓解后：
停用曲妥珠单抗患者30例（43%），中位随访78个月后仍然缓解患者20例（67%），中位进展时间15个月（四分位：10～18）。
维持曲妥珠单抗患者40例（58%），中位随访68个月后仍然缓解患者13例（33%），中位进展时间14个月（四分位：6～27）。
因此，实现影像学完全缓解是HER2阳性晚期乳腺癌患者总生存改善的最强预测因素。对于持续影像学完全缓解的患者，经过医师筛选后，或可停用曲妥珠单抗。故有必要开展进一步研究，确定哪些已经实现影像学完全缓解的患者可以安全地停用曲妥珠单抗。
Breast Cancer Res Treat. 2019 Sep 6.
Radiological complete remission in HER2-positive metastatic breast cancer patients: what to do with trastuzumab?
Steenbruggen TG, Bouwer NI, Smorenburg CH, Rier HN, Jager A, Beelen K, Ten Tije AJ, de Jong PC, Drooger JC, Holterhues C, Kitzen JJEM, Levin M, Sonke GS.
The Netherlands Cancer Institute, Amsterdam, The Netherlands; Albert Schweitzer Hospital, Dordrecht, The Netherlands; Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Reinier de Graaf Hospital, Delft, The Netherlands; Amphia Hospital, Breda, The Netherlands; Sint Antonius Hospital, Utrecht, Utrecht, The Netherlands; Ikazia Hospital, Rotterdam, The Netherlands; Haga Hospital, The Hague, The Netherlands.
PURPOSE: Patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab may experience durable tumor response for many years. It is unknown if patients with durable radiological complete remission (rCR) can discontinue trastuzumab. We analyzed clinical characteristics associated with rCR and overall survival (OS) in a historic cohort of patients with HER2-positive MBC and studied the effect of stopping trastuzumab in case of rCR.
METHODS: We included patients with HER2-positive MBC treated with first or second-line trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Data were collected from medical records. We used multivariable regression models to identify independent prognostic factors for rCR and OS. Time-to-progression after achieving rCR for patients who continued and stopped trastuzumab, and breast cancer-specific survival were also evaluated.
RESULTS: We identified 717 patients with a median age of 53 years at MBC diagnosis. The median follow-up was 109 months (IQR 72-148). The strongest factor associated with OS was achievement of rCR, adjusted hazard ratio 0.27 (95% CI 0.18-0.40). RCR was observed in 72 patients (10%). The ten-year OS estimate for patients who achieved rCR was 52 versus 7% for patients who did not achieve rCR. Thirty patients with rCR discontinued trastuzumab, of whom 20 (67%) are alive in ongoing remission after 78 months of median follow-up since rCR. Of forty patients (58%) who continued trastuzumab since rCR, 13 (33%) are in ongoing remission after 68 months of median follow-up. Median time-to-progression in the latter group was 14 months.
CONCLUSIONS: Achieving rCR is the strongest predictor for improved survival in patients with HER2-positive MBC. Trastuzumab may be discontinued in selected patients with ongoing rCR. Further research is required to identify patients who have achieved rCR and in whom trastuzumab may safely be discontinued.
KEYWORDS: HER2-positive; Long-term survival; Metastatic breast cancer; Radiological complete remission; Trastuzumab
PMID: 31493033
DOI: 10.1007/s10549-019-05427-1
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