Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Clin Cancer Res. 2019 Aug 15;25(16):4985-4992. doi: 10.1158/1078-0432.CCR-19-0560. Epub 2019 May 10.
In breast cancer, pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) is associated with favorable long-term outcome. Trastuzumab emtansine as additional adjuvant therapy improves recurrence-free survival of patients with HER2-positive breast cancer without pCR, but it is uncertain whether all patients without pCR need additional therapy. We evaluated the prognostic value of residual disease after trastuzumab-based NST in patients with HER2-positive breast cancer using Residual Cancer Burden (RCB), Neoadjuvant Response Index (NRI), and Neo-Bioscore.
We included patients with stage II or III HER2-positive breast cancer treated with trastuzumab-based NST and surgery at The Netherlands Cancer Institute between 2004 and 2016. RCB, NRI, and Neo-Bioscore were determined. Primary endpoint was 5-year recurrence-free interval (RFI). A 3% difference compared with the pCR group was considered acceptable as noninferiority margin on the 5-year RFI estimate, based on a proportional hazards model, and its lower 95% confidence boundary.
A total of 283 women were included. Median follow-up was 67 months (interquartile range 44-100). A total of 157 patients (56%) with pCR (breast and axilla) had a 5-year RFI of 92% (95% CI, 88-97); patients without pCR had a 5-year RFI of 80% (95% CI, 72-88). Patients with an RCB = 1 ( = 40, 15%), an NRI score between 0.75 and 0.99 ( = 30, 11%), or a Neo-Bioscore of 0 to 1 (without pCR; = 28, 11%) have a 5-year RFI that falls within a predefined noninferiority margin of 3% compared with patients with pCR.
The RCB, NRI, and Neo-Bioscore can identify patients with HER2-positive breast cancer with minimal residual disease (i.e., RCB = 1, NRI ≥ 0.75, or Neo-Bioscore = 0-1) after NST who have similar 5-year RFI compared with patients with pCR.
在乳腺癌中，新辅助全身治疗（NST）的病理完全缓解（pCR）与良好的长期预后相关。曲妥珠单抗-美坦新偶联物作为辅助治疗可改善无 pCR 的 HER2 阳性乳腺癌患者的无复发生存，但尚不确定所有无 pCR 的患者是否都需要额外的治疗。我们使用残余肿瘤负担（RCB）、新辅助反应指数（NRI）和 Neo-Bioscore 评估了接受曲妥珠单抗为基础的 NST 治疗的 HER2 阳性乳腺癌患者在治疗后的残余疾病的预后价值。
我们纳入了 2004 年至 2016 年在荷兰癌症研究所接受曲妥珠单抗为基础的 NST 和手术治疗的 II 期或 III 期 HER2 阳性乳腺癌患者。确定了 RCB、NRI 和 Neo-Bioscore。主要终点是 5 年无复发生存率（RFI）。基于比例风险模型及其较低的 95%置信区间边界，与 pCR 组相比，可接受的 5 年 RFI 估计值的非劣效性差异为 3%。
共纳入 283 名女性。中位随访时间为 67 个月（四分位距 44-100）。157 名（56%）患者达到了 pCR（乳腺和腋窝），其 5 年 RFI 为 92%（95%CI，88-97）；未达到 pCR 的患者 5 年 RFI 为 80%（95%CI，72-88）。RCB = 1（=40，15%）、NRI 评分在 0.75 至 0.99（=30，11%）或 Neo-Bioscore 为 0 至 1（无 pCR；=28，11%）的患者，与 pCR 患者相比，其 5 年 RFI 在预设的 3%非劣效性范围内。
RCB、NRI 和 Neo-Bioscore 可识别出接受 NST 治疗后存在最小残余疾病（即 RCB=1、NRI≥0.75 或 Neo-Bioscore=0-1）的 HER2 阳性乳腺癌患者，与 pCR 患者相比，这些患者的 5 年 RFI 相似。
