Department of Oncology-Pathology, Karolinska Institutet, Karolinska Vägen A2:07, Solna, 171 64, Stockholm, Sweden.
Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
Breast Cancer Res Treat. 2024 Apr;204(2):299-308. doi: 10.1007/s10549-023-07200-x. Epub 2024 Jan 4.
Thymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown.
In the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated.
No association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis.
sTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation.
ClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.
胸苷激酶 1（TK1）在 DNA 合成和细胞增殖中发挥关键作用。TK1 已被研究作为人表皮生长因子 2（HER2）阴性早期和转移性乳腺癌（BC）的预后标志物和治疗反应的早期指标。然而，HER2 阳性 BC 中连续 TK1 活性的预后和预测价值尚不清楚。
在 PREDIX HER2 试验中，197 名 HER2 阳性 BC 患者被随机分配至新辅助曲妥珠单抗、帕妥珠单抗和多西他赛（DPH）或曲妥珠单抗emtansine（T-DM1），然后进行手术和辅助表柔比星和环磷酰胺治疗。所有参与者均在多个时间点前瞻性采集血清样本：基线时、第 1、2、4 和 6 周期时、辅助治疗结束时、每年共 5 年，和/或复发时。评估 sTK1 活性与基线特征、病理完全缓解（pCR）、无事件生存（EFS）和无病生存（DFS）的关系。
基线 sTK1 水平与所有基线临床病理特征均无相关性。所有病例均观察到从基线到第 2 周期 TK1 活性增加。基线、第 2 和第 4 周期 sTK1 水平与 pCR 状态无关。中位随访 58 个月后，23 例患者发生 EFS 事件。基线或第 2 周期 sTK1 活性与事件时间之间无显著影响。在残留疾病（非 pCR）和治疗结束时高 sTK1 活性的患者中，观察到一种潜在的更差的长期预后的非显著趋势。
HER2 阳性 BC 新辅助治疗后 sTK1 活性增加，但与患者结局或治疗获益无关。然而，在未达到 pCR 的患者中，手术后的预后价值值得进一步研究。
ClinicalTrials.gov，NCT02568839。于 2015 年 10 月 6 日注册。
