Dynamic changes in circulating tumor DNA among Taiwanese early breast cancer patients undergoing upfront surgery: Results from the VGH-TAYLOR study.

Abstract

558 Background: Circulating tumor DNA (ctDNA) has emerged as a promising prognostic marker in breast cancer. Post-treatment ctDNA detection is associated with increased recurrence risk and reduced long-term survival. This study evaluated dynamic ctDNA changes in early breast cancer patients with distinct immunohistochemical (IHC) subtypes. Methods: Liquid biopsies were performed using the Oncomine Breast cfDNA Assay v2. Samples were collected at baseline (pre-surgery, visit 1), after adjuvant therapy (visit 2), and every six months thereafter (visit 3 and subsequent visits) for patients in the upfront surgery (Group 1A) arm of the VGH-TAYLOR study. Pre-operative and follow-up ctDNA detectability and its impact on recurrence-free survival (RFS) were evaluated. Results: A total of 577 early breast cancer patients with at least one ctDNA test were analyzed; the majority (74%, n=425) were hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative. Among 500 pre-operative samples, ctDNA was detected in 24% (n=121) of patients, with TP53 (21%, n=106) and PIK3CA (6%, n=28) being the most prevalent mutations. During follow-up (visit 2 and later), ctDNA was detected in only 3% (n=13) of patients; all harbored TP53 mutations, with one case also exhibiting an ERBB3 mutation. All patients with detectable follow-up ctDNA had also tested positive pre-operatively (Table 1). Five-year RFS was 94% in the ctDNA-positive group (n=121) and 95% in the ctDNA-negative group (n=319). Among HR-negative/HER2-positive and HR-negative/HER2-negative subtypes, ctDNA positivity was associated with numerically worse RFS (90% vs. 94% and 88% vs. 89%, respectively). Conclusions: Following surgery and adjuvant therapy, most pre-operative ctDNA-positive cases became undetectable (89%, 108/121). Although ctDNA positivity showed a trend toward compromised RFS, particularly in HR-negative/HER2-positive and HR-negative/HER2-negative subtypes with TP53 mutations, the high clearance rate of pre-surgery ctDNA positivity warrants longer follow-up to fully evaluate its prognostic value and the impact of liquid biopsy in early breast cancer. Clinical trial information: NCT04626440 . Dynamic changes of circulating tumor DNA before surgery and after treatment across immunohistochemical subtypes among early breast cancer. Subtype Pre-surgery ctDNA positive Post-treatment/follow-up ctDNA positive HR+/HER2+ 26%(9/35) 0%(0/35) HR+/HER2- 22.8%(84/369) 1.9%(7/369) HR-/HER2+ 25%(7/28) 7.1%(2/28) HR-/HER2- 30.8%(20/65) 6.2%(4/65) HR: hormone receptor, HER2: human epidermal growth factor receptor II, ctDNA: circulating tumor DNA.