Circulating Tumor DNA Linked to Poor Prognosis in HER2-Positive Early Breast Cancer

THURSDAY, Jan. 15, 2026 (HealthDay News) — For patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), the presence of circulating tumor (ct)DNA after neoadjuvant therapy (NAT) is associated with poor prognosis and may indicate the need for adjuvant ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate, according to a study published online Jan. 14 in Cancer Research Communications.

Po-Han Lin, M.D., Ph.D., from National Taiwan University Hospital in Taipei, and colleagues examined the role of ctDNA persistence in 117 patients with HER2-positive EBC who achieved pathologic complete response (pCR) after NAT in terms of predicting prognosis.

The researchers found that 25 and 92 patients achieved and did not achieve pCR after NAT, respectively. Six of 25 pCR patients and 26 of 92 patients without pCR showed positive ctDNA. Overall, 18 and 99 patients received and did not receive adjuvant T-DM1, respectively. ctDNA positivity after NAT independently predicted recurrence among the non-T-DM1 group (hazard ratio, 5.505). Shorter recurrence-free survival (RFS) was experienced by pCR patients with ctDNA positivity versus pCR and ctDNA-negative patients after NAT; compared with non-pCR patients with ctDNA-positive status, non-pCR patients with ctDNA-negative tumors had a better RFS. In the 79 patients who were ctDNA-positive before NAT, significantly better RFS was seen with ctDNA clearance by NAT versus nonclearance. In patients with ctDNA positivity after NAT during serial tests, adjuvant T-DM1 significantly improved the ctDNA clearance rate compared with non-T-DM1 therapy. On classification of patients as T-DM1/non-T-DM1 and ctDNA-positive/negative, RFS was significantly shorter in those with ctDNA-positive/non-T-DM1 than in the other groups.

“Our findings indicate that ctDNA could be a better prognostic factor than pCR in patients with HER2-positive early breast cancer after they”ve received NAT,” lead author Chiun-Sheng Huang, M.D., Ph.D., also from the National Taiwan University Hospital, said in a statement.

One author disclosed ties to the biopharmaceutical industry.

Abstract/Full Text