Retrospective Analysis of Sentinel Lymph Node Biopsy Using Methylene Blue Dye for Early Breast Cancer
Introduction
Sentinel lymph node biopsy (SLNB) has become a standard procedure for evaluating axillary lymph nodes in patients with clinically node-negative early breast cancer. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 study laid the foundation for the clinical application of SLNB, demonstrating its efficacy in predicting the pathologic status of axillary lymph nodes. The 2020 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines on Breast Cancer further endorsed SLNB as a recommended method for axillary evaluation in early breast cancer patients. In China, methylene blue dye (MBD) is the most commonly used tracer for SLNB due to the limited availability of radionuclides and isosulfan blue. This study aims to investigate the feasibility and clinical outcomes of SLNB using MBD in early breast cancer patients, focusing on the identification rate (IR), false-negative rate (FNR), and the prognostic implications of different sentinel lymph node (SLN) and non-SLN statuses.
Methods
This retrospective study analyzed the clinicopathological data of early breast cancer patients treated at Peking University First Hospital between January 2013 and December 2018. The study included female patients with clinical carcinoma in situ (cTis) to T3N0 invasive breast cancer or carcinoma in situ, who had clinically negative axillary lymph nodes on physical examination and ultrasound. Patients with stage IV breast cancer, inflammatory breast cancer, or positive axillary lymph nodes on clinical evaluation were excluded. The SLNB procedure involved the intradermal injection of 0.1 to 0.3 mL of 1% MBD into the affected areola area, followed by breast massage and axillary incision to identify blue-stained SLNs. SLNB was considered successful if one to five blue-stained lymph nodes were identified. Pathological evaluation of SLNs followed the College of American Pathologists (CAP) guidelines, with macrometastasis defined as a metastatic lesion >2.0 mm and micrometastasis as a lesion >0.2 mm and ≤2.0 mm. The FNR was calculated as the number of MBD-negative frozen sections with positive paraffin results divided by the total number of positive-SLN paraffin sections. Immunohistochemistry (IHC) and histological grading were performed according to established guidelines, and molecular subtyping was based on the 2011 St. Gallen International Expert Consensus. Follow-up data, including disease-free survival (DFS) and overall survival (OS), were collected and analyzed using Kaplan-Meier curves and Cox proportional hazards models.
Results
Between 2013 and 2018, 1603 patients with early breast cancer underwent SLNB using MBD. The SLN identification rate was 95.8% (1536/1603), with a median of two SLNs detected per patient. The SLNB failure rate was 4.2% (67/1603), including 11 cases with no blue-stained nodes and 56 cases with ≥6 nodes detected. Among the 1536 patients with successful SLNB, SLN metastasis was identified in 310 patients (20.2%), including 42 cases of micrometastasis (13.5%) and 268 cases of macrometastasis (86.5%). All 310 SLN-positive patients underwent axillary lymph node dissection (ALND), with non-SLN metastasis observed in 37.7% (117/310) of cases. The FNR in frozen sections was 6.5%, with significant differences between micrometastasis (19.0%) and macrometastasis (4.5%) groups. Multivariate analysis identified vascular tumor embolism as the only independent factor affecting SLN detection success (odds ratio: 0.440, 95% confidence interval: 0.224–0.862, P = 0.017). Survival analysis showed a significant difference in DFS between patients with non-SLN metastasis and those without (P = 0.006), although no significant difference was observed in OS (P = 0.928).
Discussion
The high SLN identification rate of 95.8% in this study demonstrates the feasibility of using MBD as a single tracer for SLNB in early breast cancer patients. This finding is consistent with previous reports on dual tracer-guided SLNB, which typically achieve IRs ranging from 81.7% to 98.0%. The low FNR of 6.5% in frozen sections further supports the reliability of MBD-guided SLNB, particularly for detecting macrometastasis (FNR: 4.5%). However, the higher FNR for micrometastasis (19.0%) highlights the limitations of frozen section analysis in identifying small metastatic lesions. The study also underscores the importance of careful preoperative ultrasound evaluation in reducing the SLN-positive rate, as detailed ultrasound assessment can help identify patients with suspected axillary node metastasis who may not require SLNB.
The prognostic analysis revealed that non-SLN metastasis significantly impacts DFS, emphasizing the need for accurate staging and appropriate treatment decisions in SLN-positive patients. The findings align with previous studies showing that non-SLN metastasis is associated with a higher risk of recurrence and metastasis. However, the lack of significant differences in OS between patients with and without non-SLN metastasis suggests that other factors, such as systemic therapy, may play a critical role in long-term survival outcomes. The study also highlights the importance of adhering to standardized pathological sampling and evaluation techniques to minimize false-negative results in frozen sections.
The use of MBD as a single tracer for SLNB offers several advantages, including cost-effectiveness, widespread availability, and ease of use. However, the study acknowledges that the number of SLNs detected with MBD is generally lower than that with dual tracers, which may limit the accuracy of nodal staging in some cases. The findings also support the recommendations of the American College of Surgeons Oncology Group Z0011 and IBCSG 23-01 studies, which suggest that certain patients with SLN metastasis may avoid ALND without compromising survival outcomes. However, the decision to omit ALND should be made cautiously, particularly in patients with ≥2 positive SLNs, SLN macrometastasis, or advanced tumor stages.
Conclusion
This retrospective study provides strong evidence supporting the use of MBD as a single tracer for SLNB in early breast cancer patients. The high SLN identification rate and low false-negative rate in frozen sections demonstrate the reliability and feasibility of this approach in clinical practice. The study also highlights the prognostic significance of non-SLN metastasis, emphasizing the need for accurate staging and individualized treatment decisions. While MBD-guided SLNB offers several advantages, further research is needed to optimize the technique and improve outcomes for patients with early breast cancer. The findings contribute to the growing body of evidence supporting the use of SLNB as a standard procedure for axillary evaluation in clinically node-negative early breast cancer patients.
doi.org/10.1097/CM9.0000000000001359
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