乳腺癌内乳前哨淋巴结活检评估预后及指导个体化内乳照射：一项长期随访研究

doi:10.19401/j.cnki.1007-3639.2023.02.007

摘要/Abstract

摘要：

背景与目的： 内乳照射（internal mammary lymph node irradiation，IMNI）可以改善内乳淋巴结（internal mammary lymph node，IMLN）高危转移患者的生存。本研究旨在探讨内乳前哨淋巴结活检（internal mammary sentinel lymph node biopsy，IM-SLNB）对评估预后及指导个体化IMNI的优势。方法： 回顾性分析2011年11月—2021年12月在3项前瞻性临床试验（NCT01642511、NCT03541278、NCT03024463）中成功行IM-SLNB的浸润性乳腺癌患者，筛选预后的独立危险因素，分析内乳前哨淋巴结（internal mammary sentinel lymph node，IMSLN）转移对预后的影响；在接受区域淋巴结照射者中分析IMNI实施状况、生存获益及对放射性肺损伤（radiation induced lung injury，RILI）的影响。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）和RILI。结果： 研究入组537例患者，中位随访60个月。IMSLN转移状况是DFS及OS的独立危险因素（P均<0.05），与IMSLN阴性组患者相比，IMSLN阳性组患者DFS及OS显著降低（P均<0.05）。IMSLN阴性患者增加IMNI并没有显著改善DFS（P = 0.099）和OS（P = 0.486），但RILI的风险显著增高（OR = 3.678，P<0.05）。对于IMSLN阳性患者，增加IMNI可显著改善5年DFS（87.3% vs 52.5%，P = 0.040），但并未转化为OS的获益（P = 0.603）。结论： IMSLN的转移状况是独立的预后因素，IMSLN转移的患者接受IMNI可显著改善预后，IMSLN未转移的患者通过豁免IMNI可在不影响预后的情况下显著降低RILI的风险。

关键词: 乳腺癌, 前哨淋巴结活检, 内乳淋巴结, 照射, 预后

Abstract:

Background and purpose: Internal mammary lymph node irradiation (IMNI) improves survival in patients with internal mammary lymph node (IMLN) high-risk metastatic breast cancer. The purpose of this study was to study the advantages of internal mammary sentinel lymph node (IMLN) biopsy (IM-SLNB) for assessing prognosis and directing individualized IMNI. Methods: This study evaluated patients recruited in three prospective clinical trials (NCT01642511, NCT03541278, and NCT03024463) from November 2011 to December 2021, assessed for prognostic risk variables based on IMSLN metastatic status and prognosis between subgroups. In patients who received regional lymph node irradiation, the implementation status, survival benefit, and influence of IMNI on radiation-induced lung injury (RILI) were studied. The primary endpoint was disease-free survival (DFS), with overall survival (OS) and RILI as secondary endpoints. Results: The study enrolled 537 patients and had a 60-month median follow-up. Patients with IMSLN metastasis had a significantly worse 5-year DFS and OS (DFS: 95.1% vs 71.4%, OS: 99.1% vs 90.1%, both P<0.05), and IMSLN metastatic status was an independent risk factor for DFS and OS (both P<0.05). Adding IMNI did not improve DFS (P = 0.099) or OS (P = 0.486) in patients with negative IMSLN, while it did increase the risk of RILI (OR = 3.678, P<0.05). However, adding IMNI improved 5-year DFS (87.3% vs 52.5%, P = 0.040) for patients with positive IMSLN but had no effect on OS (P = 0.603). Conclusion: This study discovered that IMSLN metastatic status has significant prognostic importance. Patients with IMSLN metastasis who receive IMNI have significantly improved prognosis, and patients without IMSLN metastasis have a much lower risk of RILI by being exempt from IMNI without worse prognosis.

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

中图分类号:

R737.9

陈玉光, 孙晓, 毕钊, 邱鹏飞, 段宝伟, 樊庆达, 王永胜. 乳腺癌内乳前哨淋巴结活检评估预后及指导个体化内乳照射：一项长期随访研究[J]. 中国癌症杂志, 2023, 33(2): 142-151.

CHEN Yuguang, SUN Xiao, BI Zhao, QIU Pengfei, DUAN Baowei, FAN Qingda, WANG Yongsheng. Internal mammary sentinel lymph node biopsy for breast cancer: a long-term follow-up research for assessment of prognosis and guiding individualized internal mammary lymph node irradiation[J]. China Oncology, 2023, 33(2): 142-151.

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参考文献 21

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Item	Case (n=537)	Percentage/%	Item	Case (n=537)	Percentage/%
Age	48.9±9.0 (27.0-78.0)		Grade
BMI	23.9±3.1 (16.4-39.7)		Ⅰ	9	1.7
Menopausal status			Ⅱ	326	60.7
No	331	61.6	Ⅲ	163	30.3
Yes	206	38.4	N/A	39	7.3
Laterality			No. of ALN positive
Left	305	56.8	0	263	49.0
Right	232	43.2	1-3	173	32.2
Tumor location			4-9	57	10.6
Lateral	282	52.5	≥10	44	8.2
Central/medial	248	46.2	IMSLN
Unknown	7	1.3	Negatvie	440	81.9
Pathological size/cm			Positive	97	18.1
≤2	271	50.4	ER
2-5	243	45.3	Negatvie	133	24.8
>5	23	4.3	Positive	404	75.2
Histological type			PR
Ductal	483	89.9	Negatvie	168	31.3
Lobular	15	2.8	Positive	369	68.7
Mucinous	8	1.5	HER2
Microinfiltration	23	4.3	Negatvie	380	70.8
Other special types	8	1.5	Positive	132	24.6
Lymphatic invasion			N/A	25	4.6
No	465	86.6	Tumor subtype
Yes	72	13.4	HR positive/HER2 negatvie	316	58.8
No. of IMSLN	1.8±0.9 (1-6)		HER2 positive	132	24.6
Surgery type			TNBC	64	11.9
Mastectomy	502	93.5	N/A	25	4.7
Lumpectomy	35	6.5

Variables	DFS				OS
	Univariate Cox analysis		Multivariate Cox analysis		Univariate Cox analysis		Multivariate Cox analysis
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
IMSLN (positive vs negative)	5.908 (3.194-10.928)	<0.001	3.652 (1.832-7.281)	<0.001	6.927 (2.783-17.240)	<0.001	3.232 (1.153-9.058)	0.026
Age	0.994 (0.960-1.030)	0.749			1.034 (0.984-1.086)	0.190
Menopausal status (yes vs no)	1.338 (0.721-2.480)	0.356			1.712 (0.694-4.222)	0.243
Tumor location (lateral vs central/medial)	1.622 (0.871-3.020)	0.127			1.993 (0.785-5.063)	0.147
No. of positive ALN	1.121 (1.083-1.160)	<0.001	1.090 (1.045-1.137)	<0.001	1.138 (1.082-1.196)	<0.001	1.100 (1.032-1.173)	0.003
Pathological size (cm)		0.002		0.006		<0.001		0.013
2-5 (vs≤2)	1.484 (0.760-2.899)	0.248	0.769 (0.374-1.577)	0.473	4.430 (1.250-15.700)	0.021	2.597 (0.697-9.673)	0.155
>5 (vs≤2)	5.367 (2.080-13.848)	<0.001	3.571 (1.357-9.395)	0.010	17.214 (3.850-76.970)	<0.001	9.514 (2.023-44.749)	0.004
Histological grade (Ⅲ vs Ⅰ-Ⅱ)	2.270 (1.230-4.189)	0.009	2.367 (1.273-4.400)	0.006	1.129 (0.429-2.973)	0.806
Lymphatic invasion (yes vs no)	1.106 (0.433-2.827)	0.833			1.137 (0.261-4.945)	0.864
ER (ER⁺ vs ER^-)	0.550 (0.291-1.039)	0.065			0.449 (0.180-1.115)	0.085
PR (PR⁺ vs PR^-)	0.668 (0.357-1.252)	0.208			0.575 (0.231-1.429)	0.233
HER2 (HER2⁺ vs HER2^-)	1.171 (0.583-2.353)	0.657			1.072 (0.386-2.979)	0.893
Tumor subtype		0.219				0.209
HER2+ ( vs HR⁺/HER2^-)	1.372 (0.657-2.864)	0.400			1.382 (0.463-4.124)	0.562
TN (vs HR⁺/HER2^-)	2.049 (0.902-4.653)	0.087			2.683 (0.899-8.011)	0.077
Radiotherapy (yes vs no)	1.384 0.731-2.621)	0.319			1.856 (0.686-5.024)	0.223

Item	No IMNI (n=142)	IMNI (n=101)	5-year DFS (IMNI vs no IMNI)	P value	HR (95% CI)
T₁	47	39	91.9% vs 85.5%	0.974	1.026 (0.228-4.617)
T_2-3	95	62	84.7% vs 90.3%	0.225	1.875 (0.680-5.175)
N₁	109	41	100.0% vs 92.7%	0.356	0.029 (0.000-52.000)
N_2-3	29	60	77.4% vs 74.6%	0.672	1.257 (0.435-3.633)
Ⅰ-Ⅱ	100	26	100.0% vs 95.2%	0.539	0.036 (0.000-1 486.000)
Ⅲ	42	75	82.5% vs 74.6%	0.919	0.952 (0.369-2.458)
Lateral	84	43	87.9% vs 90.1%	0.872	1.145 (0.218-6.009)
Central/medial	54	57	83.4% vs 85.8%	0.503	1.423 (0.506-3.998)
IMSLN positive	19	67	87.3% vs 52.5%	0.040	0.286 (0.087-0.943)
IMSLN negative	123	34	84.5% vs 96.5%	0.099	3.269 (0.488-21.890)

RILI	IMSLN^- (n=157)				P value	OR (95% CI)
	No IMNI (n=123)		IMNI (n=34)
	Grade 1-2	Grade 3	Grade 1-2	Grade 3
Acute pneumonitis	7 (5.7%)	0 (0.0%)	3 (8.8%)	0 (0.0%)	0.883	1.465 (0.360-5.960)
Delayed pneumonitis or fibrosis	10 (8.1%)	0 (0.0%)	10 (29.4%)	0 (0.0%)	<0.050	4.708 (1.870-11.840)
Total	17 (13.8%)		13 (38.2%)		<0.050	3.678 (1.604-8.434)
RILI	IMSLN⁺ (n=86)				P value	OR (95% CI)
	No IMNI (n=19)		IMNI (n=67)
	Grade 1-2	Grade 3	Grade 1-2	Grade 3
Acute pneumonitis	0 (0.0%)	0 (0.0%)	8 (11.9%)	0 (0.0%)	0.252	-
Delayed pneumonitis or fibrosis	2 (10.5%)	0 (0.0%)	10 (14.9%)	0 (0.0%)	0.909	1.491 (0.300-7.410)
Total	2 (10.5%)		18(26.8%)		0.234	3.122 (0.700-13.990)