乳腺癌前哨淋巴结阳性豁免腋窝清扫后区域淋巴结放疗的回顾性研究

doi:10.19401/j.cnki.1007-3639.2025.02.010

摘要/Abstract

摘要：

背景与目的：随着乳腺癌外科治疗逐步朝个体化、微创化方向发展，前哨淋巴结活检（sentinel lymph node biopsy，SLNB）已取代腋窝淋巴结清扫术（axillary lymph node dissection，ALND）成为部分早期乳腺癌患者的标准腋窝处理方法。然而，对于前哨淋巴结（sentinel lymph node，SLN）阳性未行ALND的患者是否需要区域淋巴结照射（regional lymph node irradiation，RNI），临床上尚存在争议。本研究旨在分析SLN阳性未行ALND患者的临床病理学特征及预后情况，评估RNI的临床应用价值，为此类患者的临床治疗决策提供证据支持。方法：本单中心回顾性队列研究筛选了2014年9月1日—2023年8月31日在山东省肿瘤医院接受SLNB的乳腺癌患者，所有患者均已签署治疗知情同意书。依据术后放疗是否包括区域淋巴结[内乳和（或）腋窝和（或）锁骨上下]照射野，分为RNI组和no-RNI组，并进行一系列随访。此外，根据乳房手术方式、肿瘤分子分型以及组织学分级等因素，将患者进一步划分为多个亚组，比较各亚组之间RNI的临床价值。主要终点为无区域复发生存（locoregional recurrence-free survival，LRRFS），次要终点为无浸润性疾病复发生存（invasive disease-free survival，iDFS）和总生存（overall survival，OS）率。本研究严格遵循《加强流行病学中观察性研究报告质量》（Strengthening the Reporting of Observational Studies in Epidemiology，STROBE）指南中的各项条目。结果：本研究筛选了8 328例乳腺癌患者的临床资料，根据入组和排除标准，356例患者最终纳入分析，其中RNI组186例，no-RNI组170例。两组在年龄、体重指数（body mass index，BMI）、绝经状态、肿瘤位置、病理学类型、组织学分级、淋巴管血管侵犯、雌激素受体（estrogen receptor，ER）和孕激素受体（progesterone receptor，PR）状态以及人类表皮生长因子受体2（human epidermal growth factor receptor 2，HER-2）表达情况方面差异无统计学意义（P>0.05），但RNI组患者的阳性SLN数量、肿瘤T分期和全乳切除术（total mastectomy，TM）占比显著高于no-RNI组（P=0.006、P=0.043、P<0.001）。中位随访38个月后，RNI组未观察到任何复发或转移病例，而no-RNI组的复发转移率为3.5%（6/170）。其中，4例仅出现局部区域复发，2例发生远处转移。RNI组在iDFS方面优于no-RNI组（P=0.017），但LRRFS和OS方面差异无统计学意义（P=0.051和P=0.356）。探索性亚组分析显示，肿瘤直径>2 cm（P=0.033）、分子分型为三阴性乳腺癌（triple-negative breast cancer，TNBC）（P=0.020）的患者在LRRFS方面可能从RNI治疗中获益。结论：对于某些高危患者，如肿瘤直径较大、分子分型为TNBC或non-SLN高转移风险的患者，RNI在降低乳腺癌复发转移风险方面仍然具有重要意义。临床实践中应结合患者的淋巴结残留肿瘤负荷、肿瘤的生物学行为及手术方式制定个体化的RNI策略。

关键词: 乳腺癌, 腋窝淋巴结, 前哨淋巴结活检, 区域淋巴结放疗

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

中图分类号:

R737.9

逯永晋, 石志强, 李彤, 王永胜, 邱鹏飞. 乳腺癌前哨淋巴结阳性豁免腋窝清扫后区域淋巴结放疗的回顾性研究[J]. 中国癌症杂志, 2025, 35(2): 228-236.

LU Yongjin, SHI Zhiqiang, LI Tong, WANG Yongsheng, QIU Pengfei. Retrospective study on regional lymph node radiotherapy after axillary dissection exemption in breast cancer patients with sentinel lymph node positive status[J]. China Oncology, 2025, 35(2): 228-236.

图/表 3

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	RNI (n=186)	No-RNI (n=170)	P value		RNI (n=186)	No-RNI (n=170)	P value
Age/year			0.093	Vascular invasion			0.098
Median	47 (30-75)	49 (27-75)		Yes	59 (31.7%)	40 (23.5%)
BMI			0.173	No	127 (68.3%)	130 (76.5%)
Median	24.24 (16.73-39.79)	24.59 (17.22-38.87)		Estrogen receptor			0.438
Menopause status			0.828	Negative	28 (15.1%)	20 (11.8%)
Premenopausal	116 (62.4%)	104 (61.2%)		Positive	158 (84.9%)	150 (88.2%)
Postmenopausal	70 (37.6%)	66 (38.8%)		Progesterone receptor			0.428
Laterality			0.168	Negative	41 (22.0%)	31 (18.2%)
Left	103 (55.4%)	81 (47.6%)		Positive	145 (78.0%)	139 (81.8%)
Right	83 (44.6%)	89 (52.4%)		HER-2			0.143
Tumor location			0.116	Negative	152 (81.7%)	149 (87.6%)
Lateral	116 (62.4%)	120 (70.6%)		Positive	34 (18.3%)	21 (12.4%)
Central/medial	70 (37.6%)	50 (29.4%)		Positive number of SLN			0.006
Tumour size D/cm			0.043	1	136 (73.1%)	147 (86.5%)
≤2.0	101 (54.3%)	112 (65.9%)		2	42 (22.6%)	20 (11.8%)
2.0<D≤5.0	80 (43.0%)	57 (33.5%)		3	8 (4.3%)	3 (1.8%)
>5.0	5 (2.7%)	1(0.6%)		Type of surgery			<0.001
Histological type			0.299	TM	133 (71.5%)	35 (20.6%)
IDC	176 (94.6%)	156 (91.8%)		BCS	53 (28.5%)	135 (79.4%)
Others	10 (5.4%)	14 (8.2%)
Histologic grade			0.139
Ⅰ	2 (1.1%)	2 (1.2%)
Ⅱ	127 (68.3%)	104 (61.2%)
Ⅲ	51 (27.4%)	49 (28.8%)
NA	6 (3.2%)	15 (8.8%)