Breast cancer is a prevalent cancer among women in the United States, with an estimated 322,000 new cases of invasive breast cancer and approximately 61,000 new cases of ductal carcinoma in situ projected for 2026. The disease is expected to result in around 42,140 deaths among women.
Study Findings
A clinical study has investigated the prognostic role of circulating tumor DNA (ctDNA) and its utility in guiding adjuvant therapy for HER2-positive early breast cancer. The research indicates that patients testing positive for ctDNA after neoadjuvant treatment and surgery experience worse outcomes compared to ctDNA-negative patients. This outcome was observed even in patients who achieved a pathologic complete response (pCR). The findings suggest that ctDNA serves as an independent prognostic factor and may offer an additional marker for guiding adjuvant therapy with ado-trastuzumab emtansine (T-DM1). The study, led by Lin et al., was published in Cancer Research Communications.
Methodology
Researchers conducted a retrospective analysis involving 117 patients diagnosed with HER2-positive early-stage breast cancer who had received neoadjuvant systemic therapy. Patients underwent chemotherapy with single or dual anti-HER2 antibodies, including at least four cycles of taxane chemotherapy and trastuzumab or dual HER2 blockage (trastuzumab plus pertuzumab). Following surgery, 18 of these patients received the antibody-drug conjugate T-DM1. Blood samples were collected from patients before they began neoadjuvant systemic therapy.
Results
- Out of 117 patients, 25 achieved a pCR after neoadjuvant therapy, while 92 did not. Six of the 25 pCR patients were ctDNA-positive.
- Eighteen patients received adjuvant T-DM1, and 99 did not.
- In the group not receiving T-DM1, ctDNA positivity after neoadjuvant therapy independently predicted cancer recurrence (hazard ratio [HR] = 5.505; 95% confidence interval [CI] = 1.950–15.540; P = .001).
- Patients with a pCR and ctDNA positivity demonstrated shorter recurrence-free survival compared to pCR patients who were ctDNA-negative after neoadjuvant therapy (P = .008).
- Conversely, non-pCR patients with ctDNA-negative tumors experienced better recurrence-free survival than non-pCR patients with ctDNA-positive status (P = .001).
- Among the 79 patients who were ctDNA-positive before neoadjuvant therapy, clearance of ctDNA by neoadjuvant therapy was associated with significantly improved recurrence-free survival compared to nonclearance (P < .001).
- Receipt of adjuvant T-DM1 also significantly improved the ctDNA clearance rate (P = .035) in patients with ctDNA positivity after neoadjuvant therapy during serial tests, compared with non–T-DM1 therapy.
- When classifying patients by T-DM1 use and ctDNA status, a significantly shorter recurrence-free survival was observed in ctDNA-positive/non–T-DM1 patients (P = .029) compared to the other three groups.
Conclusion and Implications
The study authors concluded that the presence of ctDNA after neoadjuvant therapy in patients with HER2-positive early breast cancer is associated with a poor prognosis and may indicate the need for adjuvant T-DM1. Chiun-Sheng Huang, MD, PhD, MPH, lead study author, stated that these findings suggest ctDNA could be a more effective prognostic factor than pCR in HER2-positive early breast cancer patients post-neoadjuvant therapy. This knowledge may inform decisions regarding the escalation or de-escalation of adjuvant therapy, although further large-scale studies or randomized trials are needed to verify these implications. The study received funding from the Taiwan National Science and Technology Council, National Taiwan University Hospital, and the Yonglin Foundation.