Benefits and Risks of Completely Removing Axillary Lymph Nodes in Breast Cancer

The Lancet Oncology published, on 6 August 2024, an analysis by de Boniface and colleagues of the phase III SENOMAC study,which found that identifying pN2-3 status (at least four nodal metastases) in breast cancer patients to establish eligibility for adjuvant (postoperative preventive) CDK4/6 inhibitor treatment through completion axillary lymph node dissection (tALND) significantly increased the risk of severe or very severe impairment in physical arm function.

Why the Study Matters 

Completion axillary lymph node dissection (tALND) is performed in breast cancer patients to determine whether cancer has spread to lymph nodes and to stage the disease more accurately. It also plays an important role in determining whether adjuvant treatment is needed.

Adjuvant therapies are additional treatments given after surgery to reduce recurrence risk. They include chemotherapy, radiotherapy, hormone therapy, and targeted therapies. In particular, CDK4/6 inhibitors such as abemaciclib are approved for patients with high-risk hormone receptor-positive, HER2-negative breast cancer. Abemaciclib stops cancer cell growth and division by targeting proteins controlling the cell cycle. Its approval is particularly important because of its potential to improve disease-free survival. However, treatment selection must account for the fact that such surgery can cause serious physical adverse effects. The benefit–risk balance must therefore be carefully assessed for every patient.

Study Details

The analysis used data from a subgroup of SENOMAC participants at centers in five European countries, randomized to tALND or sentinel lymph node biopsy alone.

Sentinel lymph node biopsy removes and examines the first one or two nodes to which cancer may spread during breast cancer surgery. It helps determine whether cancer has spread without larger operations such as axillary lymph node dissection.

The SENOMAC subgroup consisted of patients with tumor size ≤ 5 cm, estrogen receptor-positive, HER2-negative, T1-2, histological grade 1 to 2 breast cancer. They were matched with a monarchE study patient group eligible for adjuvant abemaciclib when four or more nodal metastases were identified.

The primary objective, using invasive disease-free survival event data from the monarchE cohort, was to determine how many patients would report severe or very severe physical arm dysfunction 1 year after surgery among those undergoing surgery and 2 years of adjuvant abemaciclib to prevent one invasive disease-free survival event over 5 years.

Invasive disease-free survival refers to the time a patient remains alive after treatment without cancer spreading to other parts of the body.

Results

Among 1,342 SENOMAC patients who answered questionnaires, after a median follow-up of 45.2 months, 84 of 634 patients who underwent tALND (13%) reported severe or very severe physical arm dysfunction, compared with 30 of 708 patients undergoing sentinel lymph node biopsy alone (4%) (P < 0.0001).

According to monarchE data, 104 patients would need completion axillary lymph node dissection (tALND) to prevent one invasive disease-free survival event over 5 years. However, 9 of those 104 patients were predicted to risk severe or very severe physical arm dysfunction one year after surgery.

Commentary

Performing tALND to establish eligibility for abemaciclib and prevent invasive disease-free survival events over 5 years carries a risk of severe or very severe arm adverse effects. It should therefore not be encouraged for this purpose.

The study emphasizes that tALND’s risks outweigh its benefits in low-risk breast cancer treatment and recommends favoring less invasive approaches when selecting treatment.

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• Related topic: Must All Axillary Lymph Nodes Be Removed? New Approaches in Breast Cancer