Abstract:

Background and purpose: With the progressive development of breast cancer surgery toward more individualized and minimally invasive approaches, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the standard method for axillary management in certain early-stage breast cancer patients. However, there is ongoing debate in clinical practice regarding whether regional lymph node irradiation (RNI) is necessary for patients with sentinel lymph node (SLN) positive status who have not undergone ALND. This study aimed to analyze the clinicopathological features and survival prognosis of patients with SLN-positive status who did not undergo ALND, evaluate the clinical application value of RNI, and provide evidence to support clinical treatment decisions for this group of patients. Methods: This single-center retrospective study screened breast cancer patients who underwent SLNB at Shandong Cancer Hospital from September 1, 2014, to August 31, 2023. All patients signed informed consent for treatment. Based on whether postoperative radiotherapy included regional lymph node irradiation (internal mammary and/or axillary and/or supra-/infra-clavicular fields), patients were divided into the RNI group and the no-RNI group for follow-up. Additionally, patients were further divided into multiple subgroups based on factors such as the type of breast surgery, tumor molecular subtype, and histological grade, to compare the clinical value of RNI among subgroups. The primary endpoint was locoregional recurrence-free survival (LRRFS), and the secondary endpoints included invasive disease-free survival (iDFS) and overall survival (OS). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was followed for this study. Results: Clinical data of 8 328 breast cancer patients’ were screened for this study, and after applying inclusion and exclusion criteria, 356 patients were included in the analysis, with 186 in the RNI group and 170 in the no-RNI group. There were no significant differences between the two groups in terms of age, body mass index (BMI), menopausal status, tumor location, pathological type, histological grade, vascular invasion, estrogen receptor (ER) and progesterone receptor (PR) status, and human epidermal growth factor receptor 2 (HER-2) expression (P>0.05). However, the number of positive SLNs, T stage, and the proportion of patients undergoing total mastectomy (TM) were significantly higher in the RNI group than in the no-RNI group (P=0.006, P=0.043, P<0.001). After a median follow-up of 38 months, no recurrence or metastasis was observed in the RNI group, while the recurrence and metastasis rate in the no-RNI group was 3.5% (6/170). Of these, 4 cases had local regional recurrence, and 2 had distant metastasis. The RNI group showed superior iDFS compared to the no-RNI group (P=0.017), however there was no statistically significant difference in LRRFS and OS (P=0.051 and P=0.356). Exploratory subgroup analysis indicated that patients with tumor diameter >2 cm (P=0.033) and triple-negative molecular (TNBC) (P=0.020) might benefit from RNI treatment in terms of LRRFS. Conclusion: For certain high-risk patients, such as those with larger tumor diameter, TNBC, or high non-SLN metastatic risk, RNI still plays an important role in reducing the risk of recurrence and metastasis in breast cancer. In clinical practice, an individualized RNI strategy should be developed based on the patient's residual lymph node tumor load, biological behavior of the tumor, and surgical method.

Key words: Breast cancer, Axillary lymph nodes, Sentinel lymph node biopsy, Regional lymph node radiotherapy