Editor’s Note: The European Society for Medical Oncology (ESMO), as a globally renowned academic conference in the field of oncology, announces numerous cutting-edge developments each year. The ESMO 2023 annual meeting was held from October 20th to 24th in Madrid, Spain. One of the highlights of the conference was a phase II multicenter prospective trial (243MO) on surgery exemption after neoadjuvant therapy for breast cancer, which garnered significant attention. Oncology Frontier specially invited Professor Jin Feng from the First Hospital of China Medical University to interpret this study.
Study Introduction
Neoadjuvant systemic therapy (NST) for triple-negative breast cancer (TNBC) and HER2+ breast cancer (HER2+BC) results in pathological complete response (pCR) in about 60% of patients. pCR after NST indicates a good prognosis and can be accurately determined through percutaneous image-guided vacuum-assisted core biopsy (VACB). This study explores the efficacy of exempting surgery in TNBC or HER2+BC patients who achieve pCR after NST. The primary objective is to assess whether patients with VACB-confirmed pCR can forgo subsequent breast surgery while receiving radiation therapy. Inclusion criteria include women aged ≥40 years with single-center TNBC or HER2+ invasive cancer with a tumor diameter <5cm, N0/N1 (≤4 suspicious lymph nodes on ultrasound biopsy), having received optional clinical NST, and final breast imaging showing the tumor must have shrunk to ≤2cm. Exclusion criteria include prior ipsilateral breast cancer, pregnancy, T3/T4 disease, clinical progression of breast cancer >20%, new lymph node metastasis, and distant metastasis
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Previous feasibility phase evaluations have been conducted on patients with VACB-confirmed pCR who underwent sole radiation therapy (without breast surgery) after NST (Johnson et al. JACS 2023), two-year pre-planned primary outcomes (Kuerer et al. Lancet Onc 2022), and 32.4 months of patient-reported outcomes (Johnson et al. SSO 2023). This report presents the primary research endpoint of the three-year planned ipsilateral breast tumor recurrence (IBTR) survival rate, as well as initial related secondary endpoints associated with CTCs/ctDNA testing (baseline pCR, 6 months and one year after radiation therapy). The median follow-up time was 38.4 months (IQR 27.6–51.8).
During the study recruitment period (2017-2021), out of 50 patients who underwent VACB after NST, 62% were confirmed to have pCR through VACB. The 3-year primary endpoint showed that in patients with pCR, the rate of ipsilateral breast tumor recurrence (IBTR) was 0%. In addition, the 3-year disease-free survival (DFS) and overall survival (OS) rates for this group were both 100%. The study also analyzed circulating tumor cells (CTCs) in 33 blood samples collected from patients. The results indicated that the presence of CTCs was minimal, with only a few patients testing positive at different time points, suggesting a good prognosis. Only 2 patients were positive for CTCs at baseline, 2 patients at 6 months, and 1 patient at 12 months. No patients were found to have CTCs at more than one time point. Furthermore, ctDNA testing was performed on 30 plasma samples from 12 patients. At baseline, 2 patients were positive for TP53 (1 with TNBC, 1 with HER2+/ER+), which is the only carcinogenic gene related to breast cancer that was detected. At 6 months, TP53 was cleared in the TNBC patient; while TP53 persisted in the blood sample of the HER2+ patient, no positive interaction was found between CTCs/ctDNA
Expert Commentary
In recent years, whether patients achieving pCR after neoadjuvant therapy can be exempted from surgical treatment has attracted significant attention, especially since pCR rates for HER2-positive and TNBC after neoadjuvant therapy are as high as 60-80%. Researchers have proposed that if the tumor has completely regressed, is surgery still absolutely necessary? Exempting surgery for patients with pCR could indeed greatly improve their quality of life. But is such treatment reliable and safe? What conditions must patients meet to be exempted from surgery? These questions await answers. The low IBTR rate, high DFS, and high OS rates in the third year of this study support the feasibility of exempting subsequent breast surgery in highly selected patients who achieve pCR confirmed by image-guided VACB after NST, reflecting the clinical and research pursuit of “achieving maximum therapeutic benefit with the least possible treatment.”
CTC testing has different values at different stages of breast cancer treatment. Compared to traditional imaging, it has unique advantages in helping to determine whether a tumor has been completely removed, assessing patient prognosis and survival, and serving as a biomarker for drug efficacy. Several experiments on the number of CTCs in breast cancer patients show that the higher the positive ratio of CTCs in peripheral blood, the greater the likelihood of tumor metastasis and recurrence; and the more CTCs detected in a patient, the relatively worse the prognosis. Currently, many large clinical studies both domestically and internationally integrate CTCs throughout various stages of breast cancer diagnosis and treatment. In the era of individualized treatment for breast cancer, this study provides new evidence for the potential value of CTC testing in highly selectively exempting patients from surgery and making optimal treatment decisions.
With the richness and development of systemic treatment, as well as the “boost” from CTC testing technology, there is now a practical basis for selectively exempting some patients from breast cancer surgery. Although the results of this small, non-randomized study are optimistic, we must remain rational. The current number of enrolled patients is small, and ipsilateral breast tumor recurrence events may be observed when the sample size is expanded. Therefore, assessing the effectiveness of this treatment approach still requires evaluation in larger samples and longer follow-up. Another challenge in exempting breast surgery after NST is the precise assessment of the primary lesion in the breast. Previous studies have shown that even with multi-point vacuum-assisted minimally invasive biopsy after NST, there is still a false-negative rate of 18.7% to 37% when imaging assessment reaches pCR. Therefore, exempting breast cancer from surgical treatment must be based on precise lesion assessment, which needs to be addressed and quantified in future trials.
Just as the development of breast cancer surgery follows a step-down principle, exempting breast surgery in highly selected breast cancer patients may become a new standard in the future. We have reason to believe that patients who achieve pCR after NST being exempted from breast surgery is potentially feasible and will have a positive impact on the current treatment modalities for TNBC and HER2+ breast cancer
- Professor, Chief Physician, Doctoral Supervisor
- Director of Breast Surgery Department, The First Hospital of China Medical University
- Director of the Breast Cancer Professional Committee, Liaoning Anti-Cancer Association
- Chairman of the Breast Surgery Branch, Liaoning Medical Association
- Deputy Head of the Breast Cancer Group, Oncology Branch, Chinese Medical Association
- Deputy Director of the Breast Cancer Professional Committee, China Anti-Cancer Association
- Executive Member of CSCO-BC, Chinese Society of Clinical Oncology
- Member of the Breast Surgery Group, Surgery Branch, Chinese Medical Association
- Deputy Director of the Breast Cancer Committee, Chinese Geriatrics Society
- Deputy Director of the Surgical Special Committee, Beijing Breast Disease Prevention and Treatment Society
- Leader of the Breast Surgery Group, Surgical Branch, Liaoning Medical Association
- Associate Professor and Doctoral Supervisor in the Department of Breast Surgery, The First Hospital of China Medical University
- Doctor of Oncology, Postdoctoral Researcher in Basic Medicine
- Leading Talent of Shenyang City
- Young Talent of China Medical University
- Principal investigator of 6 provincial and ministerial-level projects including the National Natural Science Foundation of China
- Recipient of the first and second prizes in Provincial Science and Technology Awards/Achievement Awards; Liaoning Province Outstanding Doctoral Dissertation
- Editorial Board Member and Secretary of the “Chinese Medical Association Clinical Practice Guidelines for Breast Surgery 2021/2022 Edition
