Abstract
PurposePrevious cohort studies have reported plasma TK1 activity (pTKa) as a potential prognostic biomarker in estrogen receptor-positive (ER+) HER2-negative (HER2−) metastatic breast cancer (MBC). In this prospective study, we report here the prognostic impact of pTKa in ER+/HER2− MBC patients treated with endocrine therapy and CDK4/6 inhibitor.Experimental designPatients were included into the prospective, ethics committee-approved ALCINA study (NCT02866149). Eligibility criteria were patients with ER+/HER2− MBC treated at Institut Curie with endocrine therapy and palbociclib. Plasma samples were obtained at baseline and after 4 weeks of treatment. pTKa was quantified by the DiviTum® assay (Biovica, Sweden).ResultsFrom May 2016 to August 2018, 103 patients treated with endocrine therapy and palbociclib were included. Patients had received a median of two prior systemic therapies for MBC (range 0–14). Median follow-up was 13.8 months (range 6–31), with median PFS and OS of 9.6 months (95%CI [7.0–11.3]) and 28 months (95%CI [23–not reached]), respectively. Median baseline pTKa was 292 Du/L (range 20–27,312 Du/L, IQR [89–853]). After adjusting for other prognostic factors, baseline pTKa remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1–1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2–1.6], p < 0.0001), and 4-week pTKa was associated with OS (HR = 1.6 95%CI [1.3–2], p < 0.0001). That survival prediction was significantly improved by the addition of baseline pTKa to clinicopathological characteristics. Adding pTKa changes at 4 weeks to baseline pTKa did not further increase survival prediction.ConclusionThis study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2− MBC patients treated with endocrine therapy and palbociclib.
Highlights
Endocrine therapy is the cornerstone of treatment of estrogen receptor-positive (ER+) HER2-negative (HER2−) breast cancer [1]
After adjusting for other prognostic factors, baseline plasma Thymidine kinase 1 (TK1) activity (pTKa) remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1–1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2–1.6], p < 0.0001), and 4-week pTKa was associated with OS (HR = 1.6 95%CI [1.3–2], p < 0.0001)
This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/ HER2− metastatic breast cancer (MBC) patients treated with endocrine therapy and palbociclib
Summary
Endocrine therapy is the cornerstone of treatment of estrogen receptor-positive (ER+) HER2-negative (HER2−) breast cancer [1]. Endocrine therapies for metastatic breast cancer (MBC) have remained largely unchanged for the past two decades. They include tamoxifen, aromatase inhibitors (AI), and fulvestrant. In preliminary studies using the same assay, serum or plasma TK1 activity (sTKa, pTKa) was reported to be a prognostic circulating biomarker in early and advanced breast cancer [9,10,11,12]. The prognostic impact of baseline serum TK1 levels and TK1 variation in response to therapy was reported in 159 samples from a phase III trial comparing AI and fulvestrant in ER+ HER2− MBC [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
