ctDNA Detected after Neoadjuvant Therapy for HER2-Positive Breast Cancer Is Associated with Inferior Outcomes and May Inform Adjuvant Therapy.
Journal
Cancer research communications
Journal Volume
6
Journal Issue
1
Start Page
105
End Page
114
ISSN
2767-9764
Date Issued
2026-01-01
Author(s)
Abstract
ctDNA has been reported as a predictor of the progression of metastatic breast cancer and recurrence in early breast cancer (EBC). This study explored whether ctDNA persistence in patients with HER2-positive (HER2+) EBC who achieved pathologic complete response (pCR) after neoadjuvant therapy (NAT) indicates a poor prognosis and the need for adjuvant T-DM1. Of the 117 patients enrolled, 25 patients achieved pCR after NAT and 92 patients did not. Six of the 25 pCR patients showed positive ctDNA after NAT, whereas 26 of the 92 non-pCR patients were ctDNA-positive. Eighteen patients received adjuvant T-DM1, whereas 99 patients did not. Among the non-T-DM1 group, ctDNA positivity after NAT independently predicted recurrence (HR, 5.505; 95% confidence interval, 1.950-15.540; P = 0.001). pCR patients with ctDNA positivity experienced a shorter recurrence-free survival (RFS) compared with pCR and ctDNA-negative patients after NAT(P = 0.008), whereas non-pCR patients with ctDNA-negative tumors had a better RFS compared with non-pCR patients with ctDNA-positive status (P = 0.001). In the 79 patients who were ctDNA-positive before NAT, clearance of ctDNA by NAT was associated with significantly better RFS than nonclearance (P < 0.001). Adjuvant T-DM1 also significantly improved the ctDNA clearance rate (P = 0.035) compared with non-T-DM1 therapy in patients with ctDNA positivity after NAT during serial tests. We classified the 117 patients as T-DM1/non-T-DM1 and ctDNA-positive/negative, and a significantly shorter RFS was observed in patients with ctDNA-positive/non-T-DM1 (P = 0.029) than in the other three patient groups. In conclusion, the presence of ctDNA after NAT in patients with HER2+ EBC is associated with a poor prognosis and may indicate adjuvant T-DM1.
Significance: Adjuvant T-DM1 can improve the survival of HER2+ EBC patients who don't achieve pCR. Our study showed that ctDNA positivity after NAT was associated with decreased RFS. ctDNA-positive status after NAT can be switched to ctDNA-negative status in patients treated with T-DM1. Patients who were ctDNA-positive and treated with T-DM1 had a similar RFS to those who were ctDNA-negative, indicating that "ctDNA positivity" could be a marker determining adjuvant T-DM1 therapy.
Type
journal article