Oncological outcomes following sentinel lymph node biopsy or targeted axillary dissection after downstaging with neoadjuvant chemotherapy

Early axillary recurrence after omission of axillary lymph node dissection (ALND) in patients who successfully downstage from N+ to ypN0 with neoadjuvant chemotherapy (NAC) is a rare event following both sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), and was not significantly lower in TAD than SLNB. The main advantage of TAD seems to be a reduction in the number of lymph nodes removed.

In node-positive patients treated with neoadjuvant chemotherapy (NAC), four prospective studies have demonstrated that the false-negative rate of sentinel lymph node biopsy (SLNB) is more than 10%. As all patients in these trials had axillary lymph node dissection (ALND), they did not provide data on axillary recurrence. Although single-centre studies have demonstrated low rates of axillary recurrence after SLNB alone, these studies are limited by small sample size and concerns about generalizability. Dual-tracer mapping, removal of at least 3 sentinel lymph nodes or the combination of SLNB with retrieval of the sampled clipped lymph node (also known as targeted axillary dissection, TAD) reduce the false-negative rate. However, whether the reduction in false-negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. There is no consensus on which axillary staging procedure should be used in this setting.

The aim of the presented study is to evaluate the rates of axillary, locoregional and any invasive recurrence in a large, real-world cohort of node-positive breast cancer patients who achieved nodal pCR with NAC, after omission of ALND. In addition, researchers sought to compare rates of axillary recurrence after SLNB with dual-tracer mapping versus TAD.

Study design

Data were collected from 19 centres in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 breast cancer who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumour or isolated tumour cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test.

Results

In total, 1144 patients treated with NAC followed by surgery received either SLNB (N= 666) or TAD (N= 478). Median patient age was 50 years and the majority of patients (57%) had clinical T2 tumours, 93% had N1 disease. Most (54%) were HER2+, and 23% were triple negative. Nodal radiotherapy was administered to 81% of patients, and was more common in patients who underwent TAD than in those who underwent SLNB (85% vs. 78%, p= 0.005). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (68% TAD vs. 65% SLNB, p= 0.14). TAD localisation was with wire in 24%, radioactive seed in 72%, ultrasound in 2.3%, or others in 1.9%. The clipped node was successfully retrieved in 99% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group (3.9 vs. 4.4, p< 0.001), as was the median number of sentinel lymph nodes (3 vs. 4, p< 0.001). Median follow-up in the SLNB arm was 4.2 years, median follow-up in the TAD arm was 2.7 years.

The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.0% (95%CI 0.49-2.0%), 2.7% (95%CI 1.6-4.1%) and 10% (95%CI 8.3-13%), respectively. The three-year cumulative incidence of any axillary recurrence did not differ between patients treated with TAD compared to SLNB (0.5% vs. 0.8%, p= 0.55). There were 2 isolated axillary recurrences in each group. Locoregional recurrence rates (0.8% vs. 1.9%, p= 0.19) and invasive recurrence rates (7.3% vs. 7.8%, p= 0.60) at 3 years did not differ between  patients treated with TAD or SLNB.

Conclusion

Early axillary recurrence after omission of ALND in node-positive patients who downstage to node negative with NAC is a very rare event. Compared to SLNB only, TAD allows for removal of fewer lymph nodes. These results support the omission of ALND in patients who successfully downstage to node-negative disease after NAC. Ongoing prospective studies will provide further insight to whether arm function and lymphoedema rates differ after different staging procedures.

Reference

Montagna G, et al. The OPBC-04/EUBREAST-06/OMA Study: Oncological Outcomes Following Sentinel Lymph Node Biopsy (SLNB) or Targeted Axillary Dissection (TAD) in Breast Cancer Patients Downstaging From Node Positive To Node Negative with Neoadjuvant Chemotherapy. Presented at SABCS 2022; Abstract GS4-02.