乳腺癌远处淋巴结转移患者能否手术
根据美国癌症联合委员会（AJCC）乳腺癌TNM分期标准第6版，乳腺癌同侧锁骨上淋巴转移被分入三期，通常推荐手术、放疗等局部区域治疗；而颈部、对侧腋窝、乳房内侧（内乳）等远处淋巴结转移仍然被分入四期，通常不推荐手术、放疗等局部区域治疗。随着化疗、内分泌治疗、靶向治疗等全身治疗的不断进步，为乳腺癌远处淋巴结转移患者创造了手术、放疗等局部区域治疗条件。不过，乳腺癌远处淋巴结转移与同侧锁骨上淋巴结转移以及其他四期乳腺癌患者相比，术后生存结局究竟如何？
2021年3月16日，《美国医学会杂志》网络开放版在线发表南京医科大学第一附属医院暨江苏省人民医院王水、周文斌等学者的研究报告，对乳腺癌远处淋巴结转移与同侧锁骨上淋巴结转移以及其他四期乳腺癌患者术后生存结局进行了比较。
该队列研究于2020年2月利用美国国家癌症研究所（NCI）监测流行病学最终结果（SEER）登记数据库对2010年1月1日～2014年12月31日期间2033例（其中白人1510例，占74.3%）年龄18～100岁（平均62.03±14.62岁、范围23.00～99.00岁）乳腺癌女性进行回顾分析，其中包括三组患者：
同侧锁骨上转移：212例（10.4%）
远处淋巴结转移：346例（17.0%）
其他四期乳腺癌：1475例（72.6%）
干预措施包括原发肿瘤手术、远处淋巴结手术、放疗。主要结局测量指标为总生存和乳腺癌相关生存。通过多因素比例风险回归模型，对年龄、种族、组织学、分子学亚型、临床分期等重要影响因素进行校正后，计算风险比。
结果，3年乳腺癌相关生存率：
同侧锁骨上转移：63.24%
远处淋巴结转移：64.54%
其他四期乳腺癌：41.20%
3年总生存率：
同侧锁骨上转移：53.46%
远处淋巴结转移：62.67%
其他四期乳腺癌：38.21%
与同侧锁骨上淋巴结转移患者相比：
远处淋巴结转移患者
乳腺癌致死亡风险相似（校正后风险比：0.81，95%置信区间：0.52～1.25，P=0.34）
全部原因死亡风险相似（校正后风险比：0.73，95%置信区间：0.51～1.05，P=0.09）
其他四期乳腺癌患者
乳腺癌致死亡风险较高（校正后风险比：1.99，95%置信区间：1.43～2.78，P<0.001）
全部原因死亡风险较高（校正后风险比：1.79，95%置信区间：1.35～2.38，P<0.001）
对于346例远处淋巴结转移患者，干预措施对死亡风险的影响：
原发肿瘤手术与否相比
乳腺癌致死亡风险较低（校正后风险比：0.17，95%置信区间：0.08～0.38，P<0.001）
全部原因死亡风险较低（校正后风险比：0.21，95%置信区间：0.12～0.39，P<0.001）
放疗与否相比
乳腺癌致死亡风险相似（校正后风险比：0.48，95%置信区间：0.22～1.05，P=0.07）
全部原因死亡风险较低（校正后风险比：0.46，95%置信区间：0.25～0.87，P=0.02）
因此，该美国患者队列回顾研究结果表明，乳腺癌远处淋巴结转移与同侧锁骨上淋巴转移相比，生存结局相似，可能同样属于区域病变而非四期，可对手术、放疗等局部区域治疗获益，故有必要对乳腺癌淋巴结转移的作用进行重新评定。根据这些结果，虽然仍有必要开展进一步研究进行证实，但是推荐对此类患者进行积极的局部区域治疗。
对此，中山大学和香港大学发表特邀评论：对于乳腺癌远处淋巴结转移，是否应该重新审视TNM分期？
JAMA Netw Open. 2021 Mar 16;4(3):e211809.
Comparison of Survival Outcomes Among Patients With Breast Cancer With Distant vs Ipsilateral Supraclavicular Lymph Node Metastases.
Pan H, Wang H, Qian M, Mao X, Shi G, Ma G, Yu M, Xie H, Ling L, Ding Q, Zhang K, Wang S, Zhou W.
The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; School of Public Health, Nanjing Medical University, Nanjing, China; The Second Affiliated Hospital of Soochow University, Suzhou, China; The Second People's Hospital of Kunshan, Suzhou, China; Pancreas Institute of Nanjing Medical University, Nanjing, Jiangsu, China.
This cohort study evaluates the association of distant vs ipsilateral supraclavicular lymph node metastases with survival among patients with breast cancer.
QUESTION: Is the survival of patients with distant lymph node metastases (DLNM) different from that in patients with ipsilateral supraclavicular lymph node metastases (ISLM) and other stage IV breast cancer?
FINDINGS: This population-based cohort study of 2033 patients with breast cancer found that compared with patients with ISLM, patients with distant metastases had significantly poorer breast cancer-specific survival and overall survival, whereas patients with DLNM had similar breast cancer-specific survival and overall survival. Primary surgery and radiotherapy were significantly associated with improved overall survival for patients with DLNM.
MEANING: These findings suggest that DLNM of breast cancer may be a regional disease, which could benefit from locoregional therapies.
IMPORTANCE: There is a lack of studies exploring whether the survival of patients with distant lymph node metastases (DLNM) is different from that of patients with ipsilateral supraclavicular lymph node metastases (ISLM) and other stage IV breast cancer.
OBJECTIVE: To assess the survival of patients with DLNM from breast cancer vs ISLM and other stage IV breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 2033 patients diagnosed with breast cancer between January 1, 2010, and December 31, 2014, from the Surveillance, Epidemiology and End Results registries database. Three groups of patients were included: (1) patients with ISLM without any distant metastasis, (2) patients with DLNM, and (3) patients with distant metastases (DLNM excluded). Patients younger than 18 years or older than 100 years were excluded. The data were analyzed in February 2020.
EXPOSURES: Surgery for primary tumor, surgery for distant lymph nodes, and radiotherapy.
MAIN OUTCOMES AND MEASURES: Overall survival (OS) and breast cancer-specific survival (BCSS).
RESULTS: Of the 2033 women (mean [SD] age, 62.03 [14.62] years [range, 23.00-99.00 years]; 1510 White participants [74.3%]) with breast cancer included in the study, 346 patients (17.0%) had DLNM, 212 (10.4%) had ISLM, and 1475 (72.6%) had distant metastases (DLNM excluded). The 3-year BCSS rates were 63.24% for ISLM, 64.54% for DLNM, and 41.20% for distant metastases. The 3-year OS rates were 53.46% for ISLM, 62.67% for DLNM, and 38.21% for distant metastases. Compared with patients with ISLM, patients with DLNM showed similar BCSS (hazard ratio [HR], 0.81; 95% CI, 0.52-1.25; P = .34) and OS (HR, 0.73; 95% CI, 0.51-1.05; P = .09), whereas patients with distant metastases showed significantly poorer BCSS (HR, 1.99; 95% CI, 1.43-2.78; P < .001) and OS (HR, 1.79; 95% CI, 1.35-2.38; P < .001). Of the 346 patients with DLNM, primary surgery (HR, 0.21; 95% CI, 0.12-0.39; P < .001) and radiotherapy (HR, 0.46; 95% CI, 0.25-0.87; P = .02) were significantly associated with improved OS.
CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that DLNM of breast cancer, with similar survival to N3c disease (indicating metastases to the ipsilateral supraclavicular lymph nodes), might be a regional disease, and reassessment of the role of lymph node metastases in breast cancer may be necessary. Given these findings, aggressive locoregional therapies for this disease are recommended, although future studies are still needed to confirm these results.
PMID: 33724394
DOI: 10.1001/jamanetworkopen.2021.1809
JAMA Netw Open. 2021 Mar 16;4(3):e212026.
Distant Lymph Node Metastases From Breast Cancer-Is it Time to Review TNM Cancer Staging?
Zou Y, Hu X, Deng X.
Sun Yat-sen University Cancer Center, Guangzhou, China; Faculty of Medicine, The University of Hong Kong, Hong Kong, China; School of Medicine, Sun Yat-sen University, Guangzhou, China.
PMID: 33724385
DOI: 10.1001/jamanetworkopen.2021.2026