Less Lymph Node Surgery May Be an Option in Locally Advanced Breast Cancer

Patients with locally advanced breast cancer whose lymph nodes appear cancer-free after chemotherapy given before surgery may be candidates for a less extensive procedure to check for remaining cancer in the armpit, according to findings published in the Journal of Clinical Oncology.

In the study, sentinel lymph node biopsy, which removes only the first few lymph nodes that drain the breast, missed remaining cancer in one of 47 patients who still had disease in their lymph nodes, as long as enough nodes were removed during the procedure. That works out to a false-negative rate of 2.1%, below the 10% threshold the researchers set as acceptable based on prior studies.

Patients with locally advanced breast cancer have historically undergone axillary lymph node dissection, a more extensive surgery that removes many lymph nodes from the armpit and has been associated with side effects such as lymphedema, a chronic swelling of the arm. Sentinel lymph node biopsy is already widely used for patients with less extensive lymph node involvement, but patients with locally advanced disease were largely excluded from the earlier studies that established its accuracy.

The study authors, led by Andrea V. Barrio, MD, a breast surgeon at Memorial Sloan Kettering Cancer Center in New York, wrote that the findings suggest the procedure "may be an appropriate way to stage the axilla," or the lymph nodes under the arm, in this group of patients.

What is locally advanced breast cancer?

Locally advanced breast cancer refers to disease that has spread to the skin or chest wall, including inflammatory breast cancer, or that involves extensive lymph node disease, such as nodes that are matted together or fixed in place, or cancer in nodes above or below the collarbone or near the breastbone.

Patients with this type of disease often receive neoadjuvant chemotherapy, meaning chemotherapy given before surgery. According to the study authors, current regimens clear cancer from the lymph nodes in 30% to 40% of these patients, which raised the question of whether all of them need extensive lymph node surgery.

How was the study designed?

Between August 2017 and December 2025, researchers at Memorial Sloan Kettering and the Miami Cancer Institute at Baptist Health South Florida screened 456 patients with locally advanced breast cancer. Of those, 369 (81%) had no lymph nodes that could be felt on physical exam after chemotherapy, and 145 enrolled and were included in the analysis.

Of the patients in the study, 44% had inflammatory breast cancer, 23% had other cancers involving the skin or chest wall, and 33% had advanced lymph node disease only. The median age was 49. Most had HER2-positive (39%) or triple-negative (28%) breast cancer.

All patients underwent sentinel lymph node biopsy using two tracers, a radioactive substance and a blue dye, to find the nodes that drain the breast. To test how accurate the biopsy was, every patient then had a full axillary lymph node dissection during the same surgery.

About half of the patients (49%) also had a small marker, called a clip, placed in a lymph node that contained cancer before treatment, so surgeons could check whether that node was removed.

What did the study find?

Surgeons found at least one sentinel lymph node in 108 patients (74%). In the remaining 37 patients (26%), the tracers did not map to any nodes.

The researchers considered the biopsy adequate when surgeons removed three or more sentinel nodes, or one to two sentinel nodes that included the clipped node. That was the case for 87 patients, or 60% of the study group.

Among those 87 patients, 46% had no cancer left in their lymph nodes after chemotherapy, known as a nodal pathologic complete response. Of the 47 patients who did have remaining cancer in their nodes, the biopsy missed it in one, resulting in the 2.1% false-negative rate.

The false-negative rate was higher when fewer nodes were removed. Among patients who had only one or two sentinel nodes removed and no clipped node retrieved, the biopsy missed remaining cancer in two of nine patients who still had disease, a false-negative rate of 22.2%.

When the researchers looked at the clipped node by itself, it missed remaining cancer in 15% of cases.

Why was mapping harder in some patients?

Surgeons were less likely to find sentinel nodes in patients whose cancer involved the breast skin or chest wall (67% for inflammatory breast cancer and 73% for other skin or chest wall disease) than in those with advanced lymph node disease only (83% to 87%), although the difference was not statistically significant.

Removing three or more sentinel nodes was also less common in patients with inflammatory breast cancer (45%) and other skin or chest wall disease (55%) compared with those with advanced lymph node disease (72% to 73%). Patients with a higher body mass index were also less likely to have three or more nodes removed.

The authors suggested that skin changes linked to advanced disease in the breast may disrupt the lymphatic channels that carry the tracers to the armpit, even after those changes appear to resolve with chemotherapy. About one-third of patients whose mapping failed had no cancer left in their nodes.

What do the findings mean for patients with inflammatory breast cancer?

Inflammatory breast cancer has long been considered a reason not to perform sentinel lymph node biopsy. In this study, 42% of patients with inflammatory breast cancer had no cancer left in their lymph nodes after chemotherapy.

Among the 20 patients with inflammatory breast cancer who had adequate mapping and remaining nodal disease, the biopsy missed cancer in one, a false-negative rate of 5%. The authors wrote that sentinel lymph node biopsy may be reasonable for patients with inflammatory breast cancer who have an excellent clinical response to treatment.

When cancer was found in the sentinel nodes, however, patients with inflammatory breast cancer tended to have more additional cancerous nodes in the rest of the armpit (a median of three, compared with one in patients without inflammatory disease). For that reason, the authors recommended that patients with any cancer in their sentinel nodes still undergo axillary lymph node dissection.

Who may still need more extensive lymph node surgery?

The researchers wrote that axillary lymph node dissection remains the standard for patients with locally advanced breast cancer when:

• The tracers do not map to any sentinel nodes.
• Fewer than three sentinel nodes are removed and the clipped node is not among them, even if those nodes show no cancer.
• Any cancer is found in the sentinel nodes.

In a summary accompanying the study, Alastair M. Thompson, MD, a consulting editor for the journal, noted that the approach was sufficient for about 60% of patients in the study and that dissection should be performed when node identification is inadequate.

What are the limitations of the study?

The study did not compare patients who received sentinel lymph node biopsy alone with those who had more extensive surgery, and it did not report long-term outcomes such as cancer recurrence or survival, since every patient also underwent full lymph node dissection.

The number of patients used to calculate the false-negative rate was modest. Because of that, the true rate could be somewhat higher than 2.1%, with the study's statistical range extending up to about 12.7%.

The authors also noted the possibility of selection bias between patients who joined the study and those who did not, although the two groups had similar stages of disease. The authors described the study as the largest known prospective study of sentinel lymph node biopsy in patients with locally advanced breast cancer.

Patients with locally advanced breast cancer who are interested in less extensive lymph node surgery may want to ask their care team whether they are a candidate for sentinel lymph node biopsy, whether a clip was placed in an affected node and how many nodes their surgeon expects to remove.

Reference

1. Barrio AV, Mautner S, Capko D, et al. "Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients Presenting With Locally Advanced Breast Cancer." Journal of Clinical Oncology. Posted: September 29, 2026. doi:10.1200/JCO-26-01114

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