Omitting Breast Surgery Stalls Cancer Recurrence in Exceptional Responders
At 5 years, 100% of patients with breast cancer who did not receive surgery had ipsilateral breast tumor relapse-free survival.
Overall, 100% of patients had ipsilateral breast tumor relapse-free survival at 5 years, and 100% experienced overall survival and disease-free survival. The median follow-up was 55.4 months.
At the 5-year analysis, there were no instances of recurrence after breast surgery for invasive cancer, and it was eliminated after neoadjuvant systemic therapy, according to results from a phase 2 trial (NCT02945579) presented at the 2025 Society of Surgical Oncology Annual Meeting.
Overall, 100% of patients had ipsilateral breast tumor relapse-free survival at 5 years, and 100% experienced overall survival (OS) and disease-free survival (DFS). The median follow-up was 55.4 months (IQR, 44-64).
From 13 patients over 3 time points, 33 blood samples were collected and evaluated for circulating tumor cells (CTC). At baseline, 2 patients were CTC-positive, 2 were positive at 6 months, and 1 at 12 months. Of note, there were no patients with CTCs detected at more than 1 time point.
Circulating tumor DNA (ctDNA) was analyzed from 12 patients with 30 plasma samples across 3 time points. At baseline, 2 patients were TP53-positive with either triple-negative (TNBC) breast cancer or HER2-positive/estrogen receptor-positive. For the patient with TNBC, TP53 was cleared at 6 months but persisted with the patient who was HER2-positive at 6 and 12 months. The presentation noted there was no positive interaction between CTCs and ctDNA that was identified.
“This new treatment approach appears safe and effective,” Henry M. Kuerer, MD, PhD, FACS, CMQ, professor and Executive Director of Breast Programs at MD Anderson Cancer Network, said during the presentation. “Additional clinical trials evaluating this approach are indicated before this new method shifts the paradigm of surgical management of breast cancer for some patients after neoadjuvant systemic therapy.”
This multicenter trial conducted at MD Anderson, the University of Pittsburgh Medical Center, the Mayo Clinic, and Levine Cancer Institute aimed to eliminate the need for breast cancer surgery in exceptional responders after having received systemic therapy. The presentation focused on results from cohort A1.
Patients with tumors that were T1/T2, N1 less than 4, and HER2-positive/triple negative were given neoadjuvant systemic therapy. After therapy and the clip replaced, the lesions must be less than 2 cm. Patients then received image-guided biopsy. If patients had no residual disease, they did not have surgery and followed up every 6 months. If residual disease was detected, they proceeded to standard surgery.
The primary end point was invasive breast tumor recurrence-free survival at 6 months, and 1, 2, 3, and 5 years. Secondary end points included the need for bx on follow-up, quality of life/cosmesis, correlation CTC and ctDNA, and OS/DFS.
Patients were included if they were a woman 40 years or older; had unicentric triple-negative disease or HER2-positive invasive 5 cm or less, N0/N1 of 4 or less abnormal axillary nodes on initial ultrasound with biopsy if suspicious; receiving any clinically chosen neoadjuvant systemic therapy; or have a tumor that [shrunk to] less than 2 cm on final breast imaging.
Patients were excluded if they had prior ipsilateral breast cancer, were currently pregnant, had T4/T3 disease, had clinical progression of 20% or more in the breast, or had new evidence of nodal metastases or distant metastases.
The trial overall included 50 patients with continuous data safety and monitoring and formal stopping rules. In patients enrolled at MD Anderson, CTCs and ctDNA were measured by pathologic complete response baseline at 6 and 12 months.
Patient-reported outcomes showed there was high comfort with participating in the trials and not continuing to surgery, increasing overtime decisional comfort. At baseline there were minimal and slight differences over time. This was consistent with 1 breast undergoing breast conservation therapy with receipt of radiotherapy. At baseline, there was high quality of life, which increased over time.
Reference
Kuerer H. Eliminating breast surgery for invasive cancer after neoadjuvant systemic therapy: 5-year outcomes on an inaugural multicenter phase 2 clinical trial. Presented at the 2025 Society of Surgical Oncology Annual Meeting. March 27-29, 2025; Tampa, FL.
