Journal of the National Cancer Center (Jun 2024)
The prognostic role of circulating tumor DNA across breast cancer molecular subtypes: A systematic review and meta-analysis
Abstract
Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.