乳腺癌内乳前哨淋巴结活检与患者预后的相关性研究

doi:10.19401/j.cnki.1007-3639.2025.04.007

摘要/Abstract

摘要：

背景与目的：乳腺癌内乳前哨淋巴结活检术（internal mammary sentinel lymph node biopsy，IMSLNB）是区域淋巴结微创诊断技术，可以提供准确的淋巴结分期并指导辅助治疗决策，但其对患者预后的影响尚不明确，导致临床应用一直存在争议。本研究旨在探讨IMSLNB在早期乳腺癌中的预后结果。方法：本研究为单中心回顾性队列研究，纳入了2016年1月1日—2021年12月31日于我院就诊的7 949例乳腺癌患者，应用倾向性评分匹配后，将患者分为IMSLNB组和no-IMSLNB组，比较两组患者的预后情况，主要研究终点为无病生存期（disease-free survival，DFS），次要研究终点为总生存期（overall survival，OS）、无区域复发生存期（regional recurrence-free survival，RRFS）、无局部复发生存期（local recurrence-free survival，LRFS）和无远处转移生存期（distant metastasis-free survival，DMFS）。本研究经山东第一医科大学附属肿瘤医院临床研究伦理委员会批准（编号：SDTHEC20130324）。结果：990例患者纳入最终分析（IMSLNB组330例，no-IMSLNB组660例），IMSLNB组54例患者发现IMSLN转移，IMSLN转移率为16.4%；其中47例伴腋窝淋巴结（axillary lymph node，ALN）转移、7例仅IMSLN转移。中位随访时间41个月结果显示，IMSLNB组3年DFS（98.4% vs 94.2%，HR=0.509，95% CI: 0.312~0.828，P=0.007）和5年DFS（92.5% vs 87.3%，HR=0.214，95% CI：0.206~0.222，P=0.011）均显著优于no-IMSLNB组，但3年OS（99.1% vs 99.4%，HR=0.618，95% CI: 0.231~1.655，P=0.338）和5年OS（98.5% vs 99.1%，HR=0.52，95% CI：0.51~0.53，P=0.392）差异无统计学意义。IMSLNB组3年RRFS显著优于no-IMSLNB组（99.09% vs 97.73%，HR=0.066，95% CI：0.061~0.071，P=0.048），但3年LRFS（99.70% vs 98.19%，HR=0.209，95% CI：0.201~0.217，P=0.130）和DMFS（95.76% vs 96.06%，HR=0.865，95% CI：0.858~0.872，P=0.820）在两组间差异均无统计学意义。DFS的探索性亚组分析显示，诊断年龄（≤50岁）、绝经状态（绝经前）、体重指数（body mass index，BMI）（≤24）、淋巴管血管侵犯（lymphatic vessel infiltration，LVI）（是）、肿瘤位置（外侧）、分子分型[激素受体阳性（hormone receptor positive，HR⁺）/人表皮生长因子受体阴性（human epidermal growth factor receptor 2 negative，HER2^-）]、病理学类型（浸润性导管癌）和ALN状态（阳性）各亚组患者可从IMSLNB显著获益（P<0.05）。结论：IMSLNB可以为早期乳腺癌患者提供更为准确的区域淋巴结分期，优化辅助放疗策略从而改善患者的RRFS和DFS，可作为区域淋巴结的微创分期技术推广应用。

关键词: 乳腺癌, 内乳淋巴结, 前哨淋巴结活检, 个体化治疗, 预后

Abstract:

Background and purpose: Internal mammary sentinel lymph node biopsy (IMSLNB) is a minimally invasive diagnostic technique for regional lymph nodes in breast cancer, which can provide accurate lymph staging and guide adjuvant treatment decision, but its clinical application has been controversial. The purpose of this study was to investigate the prognosis of IMSLNB in early breast cancer. Methods: In this study, a retrospective cohort of 7 949 patients with breast cancer from January 1, 2016 to December 31, 2021 was analyzed. After applying propensity score matching, the patients were divided into IMSLNB group and no-IMSLNB group, and the regional recurrence -free survival (RRFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) of the two groups were compared. This study was approved by the Clinical Research Ethics Committee of the Affiliated Tumor Hospital of Shandong First Medical University (approval number: SDTHEC20130324). Results: A total of 990 patients were included in the final analysis (330 in the IMSLNB group and 660 in the no-IMSLNB group). IMSLN metastasis was found in 54 patients in the IMSLNB group, including 47 patients with axillary lymph node (ALN) metastasis and 7 patients with IMSLN metastasis only. The IMSLN transfer rate was 16.4%. The median follow-up of 41 months showed that the IMSLNB group demonstrated better 3-year DFS [98.4% vs 94.2%, hazard ratio (HR)=0.509; 95% CI: 0.312-0.828, P=0.007] and 5-year DFS (92.5% vs 87.3%, HR=0.214, 95% CI: 0.206-0.222, P=0.011) compared with no-IMSLNB group. However, no significant differences were observed in 3-year OS (99.1% vs 99.4%, HR=0.618, 95% CI: 0.231-1.655, P=0.338) or 5-year OS (98.5% vs 99.1%, HR=0.52, 95% CI: 0.51-0.53, P=0.392) between the two groups. The 3-year RRFS in the IMSLNB group was better compared with the no-IMSLNB group (99.09% vs 97.73%, HR=0.066; 95% CI: 0.061-0.071, P=0.048), while no significant differences were observed in 3-year LRFS (99.70% vs 98.19%, HR=0.209; 95% CI: 0.201-0.217, P=0.130) or DMFS (95.76% vs 96.06%, HR=0.865, 95% CI: 0.858-0.872, P=0.820) between the two groups. The exploratory subgroup analysis of DFS revealed that patients in the following subgroups could significantly benefit from IM-SLNB (P<0.05): diagnosis age (≤50 years), premenopausal status, BMI (≤24), lymphovascular invasion (LVI, present), tumor location (lateral), molecular subtype [hormone receptor positive (HR⁺)/ human epidermal growth factor receptor 2 negative (HER2^-)], histological type (invasive ductal carcinoma), and axillary lymph node status (positive). Conclusion: IMSLNB can provide more accurate regional lymph node staging for early breast cancer, help optimize adjuvant radiotherapy strategies, and improve patients’ DFS and RRFS. It can be promoted as a minimally invasive staging technique for regional lymph nodes.

Key words: Breast cancer, Internal mammary lymph nodes, Sentinel lymph node biopsy, Individualized therapy, Prognosis

贾瑞杰, 石志强, 张琦, 逯永晋, 郑竣升, 孙菁, 毕钊, 孙晓, 王永胜, 邱鹏飞. 乳腺癌内乳前哨淋巴结活检与患者预后的相关性研究[J]. 中国癌症杂志, 2025, 35(4): 394-403.

JIA Ruijie, SHI Zhiqiang, ZHANG Qi, LU Yongjin, ZHENG Junsheng, SUN Jing, BI Zhao, SUN Xiao, WANG Yongsheng, QIU Pengfei. Research on the association of breast cancer patients’ prognosis with internal mammary sentinel lymph node biopsy[J]. China Oncology, 2025, 35(4): 394-403.

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参考文献 19

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Characteristic	Before PSM			After PSM
Characteristic	IMSLNB (n=335)	No-IMSLNB (n=1215)	P value	IMSLNB (n=330)	No-IMSLNB (n=660)	P value
Median age/year	49.0	50.0	NA	49.0	49.0	NA
Age IQR (Q1-Q3)/year	42.5-56.0	44.0-58.0	NA	43.0-56.3	43.0-56.0	NA
Age/year			0.329			0.787
≤50	178 (53.1)	609 (50.1)		175 (53.0)	344 (52.1)
>50	157 (46.9)	606 (49.9)		155 (47.0)	316 (47.9)
Laterality			0.515			0.928
Left	184 (54.9)	643 (53.0)		182 (55.2)	366 (55.5)
Right	151 (45.1)	572 (47.0)		148 (44.8)	294 (44.5)
Location			<0.001			0.322
Outside	183 (54.6)	805 (66.3)		178 (53.9)	389 (59.0)
Central/inside	150 (45.1)	402 (33.1)		150 (45.4)	267 (40.4)
Multiple/latent	2 (0.6)	8 (0.6)		2 (0.7)	4 (0.6)
Histopathologic type			<0.001			0.608
Ductal	296 (88.8)	946 (77.9)		293 (88.8)	593 (89.8)
Other	39 (11.2)	269 (22.1)		37 (11.2)	67 (10.2)
BMI/(kd·m^-2)			0.002			0.553
≤24	198 (58.8)	599 (41.3)		194 (58.8)	364 (55.2)
24-28	106 (31.8)	427 (35.1)		105 (31.8)	229 (34.7)
≥28	31 (9.4)	189 (15.5)		31 (9.4)	67 (10.1)
Menopause			0.117			0.413
Yes	135 (40.3)	548 (45.1)		134 (40.6)	286 (43.3)
No	200 (59.7)	667 (54.9)		196 (59.4)	374 (56.7)
LVI			0.02			0.502
Yes	90 (26.9)	255 (21.0)		88 (26.7)	163 (24.7)
No	245 (73.1)	960 (79.0)		242 (73.3)	497 (75.3)
Subtype			0.001			0.901
HR⁺/HER2^-	266 (79.4)	1 062 (87.4)		261 (79.1)	530 (80.3)
HER2⁺	36 (10.7)	80 (6.6)		36 (10.9)	67 (10.2)
TNBC	33 (9.9)	73 (6.0)		33 (10.0)	63 (9.5)
pT			0.143			0.360
T1	179 (53.6)	725 (59.7)		177 (53.6)	385 (58.3)
T2	148 (43.9)	464 (38.2)		145 (43.9)	259 (39.2)
T3	8 (2.4)	26 (2.1)		8 (2.4)	16 (2.4)
ALN status			0.025			0.371
N0	174 (51.2)	753 (62.0)		174 (52.7)	367 (55.6)
N1	85 (25.4)	290 (23.9)		83 (25.2)	152 (23.0)
N2	40 (11.9)	86 (7.1)		38 (11.5)	70 (10.6)
N3	36 (10.7)	86 (7.1)		35 (10.6)	71 (10.8)

ALN status	IMSLNB group		No-IMSLNB group		P value
ALN status	Patients n	Received IMLN-RT n(%)	Patients n	Received IMLN-RT n(%)	P value
N0	174	7 (4.0)	391	0 (0.0)	<0.001
N1	83	13 (15.7)	152	31 (15.5)	0.374
N2	38	20 (52.6)	70	45 (64.3)	0.241
N3	35	14 (40.0)	71	48 (67.6)	0.007
ALN total	330	54 (16.4)	660	124 (18.8)	0.349

Variables	Univariate		Multivariate
Variables	HR (95% CI)	P value	HR (95% CI)	P value
Group
No-IMSLNB	1		1
IMSLNB	0.509 (0.312-0.828)	0.007	0.439 (0.245-0.785)	0.006
Age/year
≤50	1
>50	1.105 (0.693-1.762)	0.675
Menopause
No	1
Yes	1.372 (0.859-2.189)	0.185
BMI/(kg·m^-2)
≤24	1
24-28	0.974 (0.595-1.595)	0.916
≥28	0.467 (0.126-1.312)	0.132
LVI
No	1		1
Yes	1.392 (1.189-3.138)	0.008	0.981 (0.586-1.641)	0.941
Laterality
Left	1
Right	0.954 (0.635-1.618)	0.954
Location
Outside	1
Central/medial	0.930 (0.578-1.496)	0.764
Multiple/latent	1.717 (0.234-12.578)	0.595
Histopathologic type
Ductal	1
Other	1.427 (0.730-2.791)	0.298
Subtype
HR⁺/HER2^-	1		1
HER2⁺	1.977 (1.049-3.726)	0.035	2.425 (1.280-4.595)	0.007
TNBC	2.168 (1.124-4.182)	0.021	2.102 (1.082-4.081)	0.028
pT
T1	1		1
T2	1.357 (0.838-2.199)	0.215	0.796 (0.482-1.313)	0.371
T3	4.688 (1.822-12.063)	0.001	2.079 (0.780-5.540)	0.143
ALN status
N0	1		1
N1	4.239 (2.109-8.521)	<0.001	4.905 (2.402-10.018)	<0.001
N2	9.144 (4.429-18.880)	<0.001	13.085 (5.642-30.348)	<0.001
N3	8.409 (4.010-17.635)	<0.001	9.940 (4.501-21.950)	<0.001

Clinical trial	EORTC 22922/10925	MA.20	DBCG-IMN
Enrollment n	4 004	1 832	3 089
ALN positive rate
0	44%	10%	0%
1-3	43%	85%	60%
>3	13%	5%	40%
Group	IM-MS RT vs No-IM-MS RT	RNI vs No-RNI	IMNI (right) vs no-IMNI (left)
Follow-up t/year	15.7	10	15
Result	OS (73.1% vs 70.9%, P=0.36); DFS (60.8% vs 59.9%, P=0.18); DMFS (70.0% vs 68.2%, P=0.18); Mortality (16.0% vs 19.8%, P=0.006)	OS (82.8% vs 81.8%, P=0.38); DFS (82.0% vs 77.0%, P=0.001); DMFS (86.3% vs 82.45, P=0.03)	OS (60.1% vs 55.4%, P=0.007); DMFS (35.6% vs 38.6%, P=0.04); Mortality (31.7% vs33.9%, P=0.05)