Grabau D, Jensen M B, Rank F, Blichert-Toft M
DBCG Secretariat, Copenhagen University Hospital, Copenhagen, Denmark.
APMIS. 2007 Jul;115(7):828-37. doi: 10.1111/j.1600-0463.2007.apm_442.x.
The purpose of this study was to estimate the incidence and prognostic value of axillary lymph node micrometastases (Nmic) of 2 mm or less in breast carcinomas. Results are based on data from the Danish Breast Cancer Cooperative Group (DBCG). The study was carried out as a nationwide, population-based trial with a study series consisting of 6,959 women under 75 years of age registered in the national DBCG data base from 1 January 1990 to 31 October 1994. All patients had contracted operable primary breast carcinoma, stage I-III, classified according to the TNM system as T1-T3, N0-N1, M0. Women with four or more metastatic axillary lymph nodes were excluded. All patients were treated systematically according to approved national guidelines and treatment protocols. Metastases were recognized microscopically on haematoxylin and eosin-stained sections. In case of doubt immunohistochemical staining for cytokeratin was performed. There was no serial sectioning. Micrometastases were tumour deposits of 2 mm or smaller, and accordingly included deposits of 0.2 mm and smaller. With a median observation time of 10 years and 2 months, women with Nmic (N=427) experienced a significantly worse overall survival (OS) compared with node-negative (Nneg) women (N=4,767) (relative risk (RR)=1.20, 95% CI: 1.01-1.43), irrespective of menopausal status. Women with macrometastases (Nmac) (N=1,765) had significantly worse final outcome than women with Nmic (RR=1.54, 95% CI: 1.29-1.85), irrespective of menopausal status. Multivariate analysis adjusted for patient-, histopathologic-, and loco-regional therapeutic variables showed that cases with Nmic had a significantly higher risk of death relative to Nneg cases (adjusted RR=1.49, 95% CI: 1.18-1.90). Interaction analysis showed that the number of nodes examined had a significant impact on adjusted relative risk of death according to axillary status. Furthermore, the number of nodes involved significantly influenced adjusted risk of death in the Nmic compared to the Nmac series. In conclusion, the results of the present study revealed worse final outcome in women with Nmic compared with Nneg, where all Nmic cases received adjuvant systemic treatment. Interaction analysis showed that the number of retrieved axillary nodes and the number of affected nodes had a different influence on survival related to axillary status. The different risk pattern in Nmic vs Nmac patients indicates that Nmic cases do not show the traditional risk pattern as revealed by the Nmac cases, in which increasing number of positive nodes is associated with an orderly increasing adjusted RR.
本研究的目的是评估乳腺癌中2毫米及以下腋窝淋巴结微转移（Nmic）的发生率及预后价值。研究结果基于丹麦乳腺癌协作组（DBCG）的数据。该研究作为一项全国性的基于人群的试验开展，研究系列包括1990年1月1日至1994年10月31日在国家DBCG数据库中登记的6959名75岁以下女性。所有患者均患有可手术的原发性乳腺癌，I - III期，根据TNM系统分类为T1 - T3、N0 - N1、M0。有四个或更多转移性腋窝淋巴结的女性被排除。所有患者均按照批准的国家指南和治疗方案进行系统治疗。转移灶通过苏木精和伊红染色切片在显微镜下识别。如有疑问，则进行细胞角蛋白免疫组化染色。未进行连续切片。微转移是指2毫米或更小的肿瘤沉积物，因此包括0.2毫米及更小的沉积物。中位观察时间为10年零2个月，与无淋巴结转移（Nneg）的女性（N = 4767）相比，有Nmic的女性（N = 427）总体生存率（OS）显著更差（相对风险（RR）= 1.20，95%置信区间：1.01 - 1.43），无论绝经状态如何。有大转移灶（Nmac）的女性（N = 1765）的最终结局比有Nmic的女性显著更差（RR = 1.54，95%置信区间：1.29 - 1.85），无论绝经状态如何。对患者、组织病理学和局部区域治疗变量进行多因素分析后显示，与Nneg病例相比，有Nmic的病例死亡风险显著更高（调整后RR = 1.49，95%置信区间：1.18 - 1.90）。交互分析表明，检查的淋巴结数量对根据腋窝状态调整后的死亡相对风险有显著影响。此外，与Nmac系列相比，受累淋巴结数量对Nmic病例调整后的死亡风险有显著影响。总之，本研究结果显示，与Nneg女性相比，有Nmic的女性最终结局更差，所有有Nmic的病例均接受了辅助全身治疗。交互分析表明，获取的腋窝淋巴结数量和受累淋巴结数量对与腋窝状态相关的生存有不同影响。Nmic与Nmac患者的不同风险模式表明，Nmic病例未表现出Nmac病例所显示的传统风险模式，在Nmac病例中，阳性淋巴结数量增加与调整后RR有序增加相关。
