Yuan Jia-Qi, Xiao Zhi, Wang Shou-Man, Guo Lei
Clinical Research Center for Breast Cancer Control and Prevention in Hunan Province, Multidisciplinary Breast Cancer Center, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
Gland Surg. 2022 Feb;11(2):451-465. doi: 10.21037/gs-22-52.
This study sought to estimate the prognostic effect of intratumoral heterogeneity (ITH) and Yes-associated protein 1 (YAP1) intensity in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. We also investigated individualized adjuvant therapy for YAP1-sufficient patients and HER2 heterogeneous patients.
The relationship between prognostic outcomes and clinicopathological variables in 1,650 retrieved breast cancer patients was evaluated. The HER2 intensity and YAP1 expression in HER2-ITH and non-ITH (NITH) patients were also estimated. All patients were followed-up, regardless of whether or not they received intensive treatment, to explore individualized adjuvant therapy for YAP1-sufficient patients and HER2 heterogeneous patients.
Over-expression and nuclear localization of YAP1 were significant in HER2-ITH patients. The over-expression of YAP1 and the presence of ITH affected the prognosis of HER2 positive patients. YAP1 intensity and lymph nodes metastases was more obviously affected the survival of HER2-ITH patients, while the prognosis of NITH patients were correlated with clinical Tumor-Node-Metastasis (cTNM) stage and lymph-vascular space invasion (LVSI) status. HER2-NITH patients and YAP1-insufficient patients benefited from a combination of Trastuzumab and Pertuzumab/Lapatinib, while Capecitabine significantly decreased the relapse risk of ITH patients and YAP1-sufficient patients.
YAP1 overexpression and nuclear localization was usually observed in HER2-ITH patients. For HER2-NITH patients, an advanced stage of cTNM and LVSI status increased the recurrent risk, and intensified Pertuzumab or Lapatinib treatment (combination with Trastuzumab) improved their survival. For HER2-ITH patients, the overexpression of YAP1 and pathological lymph nodes (pLN) metastases increased recurrent risk, and intensified Capecitabine treatment improved their survival. YAP1 overexpression contributed to a poor prognostic outcome, especially when HER2 signal intensity was insufficient.
本研究旨在评估肿瘤内异质性（ITH）和Yes相关蛋白1（YAP1）强度对人表皮生长因子受体2（HER2）阳性乳腺癌患者的预后影响。我们还研究了针对YAP1充足患者和HER2异质性患者的个体化辅助治疗。
评估了1650例检索到的乳腺癌患者的预后结果与临床病理变量之间的关系。还评估了HER2-ITH和非ITH（NITH）患者的HER2强度和YAP1表达。所有患者均接受随访，无论是否接受强化治疗，以探索针对YAP1充足患者和HER2异质性患者的个体化辅助治疗。
YAP1的过表达和核定位在HER2-ITH患者中显著。YAP1的过表达和ITH的存在影响HER2阳性患者的预后。YAP1强度和淋巴结转移对HER2-ITH患者的生存影响更明显，而NITH患者的预后与临床肿瘤-淋巴结-转移（cTNM）分期和淋巴管间隙浸润（LVSI）状态相关。HER2-NITH患者和YAP1不足患者从曲妥珠单抗和帕妥珠单抗/拉帕替尼联合治疗中获益，而卡培他滨显著降低了ITH患者和YAP1充足患者的复发风险。
YAP1过表达和核定位通常在HER2-ITH患者中观察到。对于HER2-NITH患者，cTNM晚期和LVSI状态增加复发风险，强化帕妥珠单抗或拉帕替尼治疗（与曲妥珠单抗联合）可改善其生存。对于HER2-ITH患者，YAP1过表达和病理淋巴结（pLN）转移增加复发风险，强化卡培他滨治疗可改善其生存。YAP1过表达导致预后不良，尤其是当HER2信号强度不足时。
