Hyogo College of Medicine, Department of Surgery, Division of Breast and Endocrine Surgery, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan.
The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Breast Medical Oncology, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
BMC Cancer. 2018 Oct 16;18(1):982. doi: 10.1186/s12885-018-4888-2.
Although peripheral blood-based parameters (PBBPs) are reported as prognostic indicators in patients with breast cancers, their utility has not been studied in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). Tumor-infiltrating lymphocytes (TILs) might be a predictive factor in patients with HER2-positive ABC treated with pertuzumab and trastuzumab (PT) plus docetaxel. We aimed to evaluate whether PBBPs could have predictive value in HER2-positive ABC treated with pertuzumab and trastuzumab (PT) combined with eribulin (ERI) or nab-paclitaxel (Nab-PTX).
Data from 51 patients included in two single-arm, phase II trials were included in this retrospective-prospective study; the ERI + PT (N = 30) and Nab-PTX + PT (N = 21) combinations were registered under clinical trials number UMIN000012375 and UMIN000006838, respectively. We assessed PBBPs using prospectively collected data and investigated the association with progression-free survival (PFS); we evaluated absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The cutoff values for ALC, NLR, and PLR were set at 1000 or 1500 cells/μL, 2, and 250, respectively.
PFS was significantly improved in patients with ALC ≥1500/μL compared to those with ALC 1000-, <1500/μL or ALC < 1000/μL (P = 0.0106). High baseline ALC was significantly associated with improved PFS (≥1500/μL; hazard ratio [HR]: 0.3715; 95% confidence interval [CI]: 0.1735-0.7955; P = 0.0108). In contrast, improved PFS was not significantly associated with NLR or PLR. Improved PFS in patients with ALC ≥1500/μL was observed irrespective of visceral metastasis or chemotherapy regimen.
Our results showed that baseline ALC was a predictive factor for PFS in HER2-positive ABC treated with PT irrespective of combined chemotherapy regimen. Anti-tumor effects might be mediated not only by the tumor microenvironment, but also by systemic peripheral circulating lymphocytes. Baseline systemic parameters such as peripheral lymphocyte count might be beneficial in addition to disease extent for predicting the efficacy of PT treatment.
UMIN000012375 , registration date: 21NOV2013, and UMIN000006838 , registration date: 6DEC2011.
尽管外周血参数（PBBPs）已被报道为乳腺癌患者的预后指标，但在人表皮生长因子受体 2（HER2）阳性晚期乳腺癌（ABC）患者中，其应用尚未得到研究。肿瘤浸润淋巴细胞（TILs）可能是接受曲妥珠单抗和帕妥珠单抗（PT）联合多西他赛治疗的 HER2 阳性 ABC 患者的预测因子。我们旨在评估 PBBPs 是否可在接受曲妥珠单抗和帕妥珠单抗（PT）联合艾立布林（ERI）或白蛋白结合型紫杉醇（Nab-PTX）治疗的 HER2 阳性 ABC 患者中具有预测价值。
本回顾性前瞻性研究纳入了两项单臂、II 期临床试验中的 51 例患者的数据；ERI+PT（N=30）和 Nab-PTX+PT（N=21）联合方案分别在临床试验注册号 UMIN000012375 和 UMIN000006838 下进行了注册。我们使用前瞻性收集的数据评估了 PBBPs，并研究了其与无进展生存期（PFS）的关联；我们评估了绝对淋巴细胞计数（ALC）、中性粒细胞与淋巴细胞比值（NLR）和血小板与淋巴细胞比值（PLR）。将 ALC、NLR 和 PLR 的截断值分别设定为 1000 或 1500 个/μL、2 和 250。
与 ALC 为 1000、<1500/μL 或 ALC <1000/μL 的患者相比，ALC≥1500/μL 的患者的 PFS 显著改善（P=0.0106）。基线时较高的 ALC 与 PFS 改善显著相关（ALC≥1500/μL；风险比 [HR]：0.3715；95%置信区间 [CI]：0.1735-0.7955；P=0.0108）。相反，NLR 或 PLR 与 PFS 改善无显著相关性。在 ALC≥1500/μL 的患者中，无论是否存在内脏转移或化疗方案，均观察到 PFS 改善。
我们的结果表明，在接受 PT 治疗的 HER2 阳性 ABC 患者中，基线 ALC 是 PFS 的预测因子，与联合化疗方案无关。抗肿瘤作用不仅可能通过肿瘤微环境介导，还可能通过全身外周循环淋巴细胞介导。除了疾病程度外，基线全身参数（如外周淋巴细胞计数）可能有助于预测 PT 治疗的疗效。
UMIN000012375，注册日期：21NOV2013，和 UMIN000006838，注册日期：6DEC2011。
