Response to Primary Systemic Therapy Could Dictate Whether Extensive Lymph Node Removal Is Needed in Patients With Breast Cancer

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Extensive removal of the lymph nodes may be safely avoided in patients with breast cancer that has metastasized to the axillary nodes if treatment is tailored to their response to therapies such as chemotherapy prior to surgery, according to new findings presented by van Hemert et al at the 2024 European Breast Cancer Conference (EBCC) (Abstract 14) and simultaneously published in the European Journal of Cancer.


Although primary systemic therapy has recently improved, and up to 70% of patients achieved a pathologic complete response, surgeons may still remove all of the axillary lymph nodes.

“The pathologist would say: ‘[We] have removed 18 lymph nodes and none of them contained residual tumor cells.’ So this raised the question: did we do the right thing for the patient by removing so many nodes with all the ensuing complications? If we are able to predict the response based on the removal of only one lymph node, it means we can safely avoid extensive removal of the lymph nodes if no living tumor cells are left. This will avoid serious complications such as … lymphedema,” emphasized lead study author Annemiek van Hemert, MD, MSc, a PhD student in the Department of Surgical Oncology at the Antoni van Leeuwenhoek–Netherlands Cancer Institute in Amsterdam. “However, although clinicians use a number of staging techniques to predict the response, until now, robust data on cancer outcomes have been lacking—especially in patients whose cancer has spread to more than three lymph nodes,” she added.

Study Methods and Results

In the new study, researchers recruited 218 patients with breast cancer between 2014 and 2021 to analyze the cancer recurrence and survival outcomes following the implementation of the Marking Axillary Lymph Nodes With Radioactive Iodine Seeds (MARI) protocol.

“We focused on patients with more extensive axillary lymph node disease: the patients where we know there were cancer cells in more than three nodes,” explained Dr. van Hemert.  

The researchers used fluorodeoxyglocuse–positron-emission tomography/computed tomography (FDG-PET/CT) scans to assess the extent of cancer metastasis to the lymph nodes. They then marked the largest axillary lymph node with a radioactive iodine seed, treated the patients with either chemotherapy or targeted therapies as part of their primary systemic therapy, and performed surgery to remove only the marked lymph node (MARI node) and examine it for residual tumor cells.

“Whenever the MARI node showed there were no residual tumor cells, in other words a pathologic complete response to the primary systemic treatment, then we did not remove any additional lymph nodes. Patients who had residual disease in the MARI node had further lymph nodes removed [through] axillary lymph node dissection. All patients received radiation treatment,” Dr. van Hemert noted.

The MARI protocol had a false-negative rate of 7%. After an average follow-up of 44 months (range = 26–62 months), the rate of cancer recurrence in the axillary nodes was 2.9% among the 103 patients who received radiation alone with no further lymph node removal. Additionally, the overall survival rate was 95% and the recurrence-free survival rate was 89%

“This means that we can safely omit the extensive removal of axillary lymph nodes in patients who achieve a [pathologic complete response] in the MARI node after primary systemic treatment,” emphasized Dr. van Hemert.

Among the 115 patients (53%) who required further lymph node removal, the axillary recurrence rate was 3.5%, the overall survival rate was 90%, and the disease-free survival rate was 82%.


“We hope that other clinicians will think of implementing this de-escalation strategy so that more patients with breast cancer will benefit from what we have shown: surgical removal of axillary nodes can be safely omitted in around 80% of patients treated with primary systemic therapy,” Dr. van Hemert highlighted.

The researchers plan to collect further data on the patients’ outcomes over a longer period of time. They also initiated the DESCARTES trial to investigate the safety of omitting radiation therapy in a selected group of patients with tumors smaller than 2 cm in diameter, no evidence of cancer metastasis to the lymph nodes, and pathologic complete response following primary systemic therapy.

“When we treat patients for breast cancer, it is important to ensure that treatment itself causes as little harm to the patients as possible. The results from this study suggest a way to help us avoid side effects that affect the quality of life and can sometimes cause considerable long-term distress to patients. Every day, we cure patients—making sure they live long lives—but at the same time, we should care also about survivorship issues. We look forward to further results from this trial,” concluded Fiorita Poulakaki, MD, PhD, FEBS, CEBS, Head of the Department of Breast Surgery at Athens Medical Center Hospital in Greece, Vice President of Europa Donna–the European Breast Cancer Coalition, and Co-Chair of the 2024 EBCC, who was not involved in the research.

Disclosure: The research in this study was funded by Stichting Herja and Stichting Reggeborgh. For full disclosures of the study authors, visit

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