Omitting Axillary Lymph Node Dissection in Patients with Clinically Positive Axillary Lymph Nodes Treated with Neoadjuvant Chemotherapy

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 284,200 new cases of breast cancer will be diagnosed in 2021 and about 44,130 individuals will die of the disease, largely due to metastatic recurrence.

Patients with locally advanced breast cancer with clinically positive axillary lymph nodes often receive chemotherapy in the neoadjuvant settings, and approximately 30-40% of patients achieve a pathological Complete Response (pCR), with eradication of disease in the axilla. In addition to increasing the likelihood of tumor resectability and breast preservation, patients achieving a pCR following neoadjuvant chemotherapy have a longer Event Free Survival (EFS) and Overall Survival (OS).

Previously published prospective trials have demonstrated that breast cancer patients with clinically positive axillary lymph nodes, who disease following neoadjuvant therapy is converted to clinically node negative disease, can safely undergo Sentinel Lymph Node Biopsy (SLNB) rather than axillary lymph node dissection, as the false negative rates are less than 10%, when 3 or more sentinel lymph nodes are retrieved. However, the rates of axillary lymph node recurrence in this population, has remained unclear. The purpose of this study was to evaluate axillary nodal recurrence rates in a consecutive cohort of breast cancer patients with clinically positive axillary lymph nodes, treated with neoadjuvant chemotherapy, who had negative disease following treatment, on Sentinel Lymph Node Biopsy.

This study included 769 patients with Stage II-III, biopsy-proven, node-positive breast cancer, of whom 610 patients were eligible for Sentinel Lymph Node Biopsy following neoadjuvant chemotherapy. Ninety one percent (N=555) converted to clinical node negative disease on physical examination, following neoadjuvant chemotherapy and 513 patients had 3 or more SLNs retrieved. Overall Axillary Lymph Node Dissection was avoided in 234 patients with 3 or more pathologically negative sentinel lymph nodes. The median patient age in this study cohort of 234 patients was 49 years. Median tumor size was 3 cm, 62% were HER2-positive, and 18% were triple negative. Majority of the patients (91%) received Doxorubicin-based neoadjuvant chemotherapy, 88% received adjuvant Radiotherapy (RT), and 70% of these patients also received nodal RT. The Primary outcome was the nodal recurrence rate among breast cancer patients with clinically positive axillary lymph nodes, treated with Sentinel Lymph Node Biopsy alone after neoadjuvant chemotherapy. Nodal recurrence was defined as a recurrence in the ipsilateral axillary, supraclavicular, or internal mammary nodal basins. Local recurrence was defined as an ipsilateral breast tumor recurrence. Distant failure included any distant metastases.

At a median follow up of 40 months, there was 1 axillary nodal recurrence, synchronous with local recurrence, in a patient who refused Radiation Therapy. Among patients who received Radiation Therapy (N=205), there were no nodal recurrences. The 5-year distant Recurrence Free Survival was 92.7%. The 5-year Overall Survival was 94.2%.

It was concluded from this study that in patients with clinically positive axillary lymph nodes, rendered clinically node negative with neoadjuvant chemotherapy, with 3 or more pathologically negative sentinel lymph nodes on Sentinel Lymph Node Biopsy alone, nodal recurrence rates were low without routine Axillary Lymph Node Dissection. These findings support surgical de-escalation by omitting Axillary Lymph Node Dissection in patients with clinically positive axillary lymph nodes, treated with neoadjuvant chemotherapy.

Nodal Recurrence in Patients with Node-Positive Breast Cancer Treated With Sentinel Node Biopsy Alone After Neoadjuvant Chemotherapy—A Rare Event. Barrio AV, Montagna G, Mamtani A, et al. JAMA Oncol. Published online October 7, 2021. doi:10.1001/jamaoncol.2021.4394