Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
Breast Cancer Res Treat. 2019 Dec;178(3):597-605. doi: 10.1007/s10549-019-05427-1. Epub 2019 Sep 6.
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.
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.
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.
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.
接受曲妥珠单抗治疗的 HER2 阳性转移性乳腺癌（MBC）患者可能会获得多年的持久肿瘤缓解。尚不清楚是否可以停止曲妥珠单抗治疗那些具有持久完全缓解（rCR）的患者。我们分析了在 HER2 阳性 MBC 患者的历史队列中与 rCR 和总生存（OS）相关的临床特征，并研究了在 rCR 情况下停止曲妥珠单抗的效果。
我们纳入了 2000 年至 2014 年期间在荷兰 8 家医院接受一线或二线曲妥珠单抗治疗的 HER2 阳性 MBC 患者。数据来自病历。我们使用多变量回归模型来确定 rCR 和 OS 的独立预后因素。对继续和停止曲妥珠单抗治疗并达到 rCR 的患者的进展时间以及乳腺癌特异性生存也进行了评估。
我们确定了 717 名 MBC 诊断时中位年龄为 53 岁的患者。中位随访时间为 109 个月（IQR 72-148）。与 OS 相关性最强的因素是达到 rCR，调整后的风险比为 0.27（95%CI 0.18-0.40）。72 名患者（10%）观察到 rCR。达到 rCR 的患者的 10 年 OS 估计为 52%，而未达到 rCR 的患者为 7%。30 名 rCR 患者停止了曲妥珠单抗治疗，其中 20 名（67%）在 rCR 后中位 78 个月的持续缓解中仍存活。在 rCR 后继续曲妥珠单抗治疗的 40 名患者（58%）中，有 13 名（33%）在中位 68 个月的随访中仍处于缓解状态。后一组的中位进展时间为 14 个月。
在 HER2 阳性 MBC 患者中，达到 rCR 是改善生存的最强预测因素。在选择的持续 rCR 患者中，可以停用曲妥珠单抗。需要进一步研究以确定达到 rCR 且曲妥珠单抗可能安全停用的患者。
