Can ctDNA Testing Predict Recurrence in HER2-Positive Breast Cancer?
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Does a "Complete Response" (pTY) in breast cancer treatment always mean a complete cure? Cancer Research Communicationspublished a striking study demonstrating that circulating tumor DNA (ctDNA) may be a 5.5-fold stronger predictor of recurrence than pathology reports.
Why Does It Matter?
Preoperative (neoadjuvant) chemotherapy and targeted drugs have become standard in breast cancer, particularly HER2-positive disease. Complete disappearance of the tumor at surgery after treatment—pathological complete response (pCR)—has long been considered the strongest sign of recovery.
In practice, however, some patients achieving pCR unfortunately relapse months or years later. This raises the concept of "invisible disease remaining at a microscopic level" (MRD) . Published by Lin and colleagues on January 14, 2026, in Cancer Research Communications , this study demonstrates that tracking circulating tumor DNA (ctDNA) through liquid biopsy could be vital for revealing hidden danger and selecting patients for powerful treatments such as T-DM1 (Kadcyla).
Study Basics: Who Received What?
This retrospective study examined patients receiving neoadjuvant (preoperative) systemic treatment: 117 patients with early-stage HER2-positive breast cancer .
- Treatment Regimen: Patients received standard taxane-based chemotherapy and anti-HER2 antibodies (trastuzumab or trastuzumab + pertuzumab).
- The KATHERINE Trial's Influence: In 18 patients without pathological complete response after surgery, meaning residual tumor remained, the survival-improving antibody–drug conjugate T-DM1 (Ado-trastuzumab emtansine) was administered.
- Follow-up: Researchers analyzed ctDNA in blood samples collected before and after treatment and examined its relationship with recurrence.
Striking Results: A 5.5-Fold Increase in Risk!
The findings could fundamentally change oncology follow-up strategies:
Risk Analysis by Patient Group
- Pathological Response "Complete," Molecular Response "Incomplete": Among 25 patients whose tumors appeared completely absent at surgery (pCR), 6 (24%) remained ctDNA-positive. They had significantly worse survival than ctDNA-negative patients with pCR (P = .008). In other words, even when pathology said "clear," the blood test said "risk remains."
- The Worst-Case Scenario: Patients with both residual tumor at surgery (non-pCR) and circulating ctDNA had the highest recurrence risk (P = .001).
- The Clearance Effect of T-DM1: Adjuvant T-DM1 recipients had significantly higher ctDNA clearance than nonrecipients (P = .035). This is evidence that the drug eliminates disease at the molecular level.
Expert Opinion: Personalizing Treatment
—Prof. Chiun-Sheng Huang (Director, Breast Care Center, National Taiwan University Hospital)
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The Future of Oncology: "Molecular Detective Work"
Dear colleagues and readers, this study is among the clearest signs of oncology's paradigm evolving from "Anatomical Pathology" to "Molecular Monitoring" .
Why Does It Matter?
We used to say, "The tumor is gone at surgery, so our work is done." This study instead says, "Set aside the microscope and examine the blood." A patient appearing entirely clear at surgery cannot be considered cured if tumor DNA remains in the blood.
What Will It Mean for Clinical Practice?
In light of these data, future discussions will consider giving powerful antibody–drug conjugates such as T-DM1 (Kadcyla) or perhaps T-DXd (Enhertu) not only to patients with pathological residual disease, but also to high-risk patients whose ctDNA remains positive despite complete pathological response. This will be a revolutionary step in deciding whom to treat more or less intensively.