Significance of axillary lymph node metastasis in primary breast cancer

Purpose: Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. yet, it is not known whether metastasis ta the axillary nodes is simply a time-dep endent variable or also a marker for a more aggressive tumor phenotype, The purpose of this study was to determine whether nodal status at initial dia gnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype, Patients and Methods: Survival experience after first relapse in 1,696 prim ary breast cancer cases was analyzed using Cox proportional hazards regress ion. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to th ree v four or more), hormone receptor status (any estrogen receptor [ER] ne gativity v ER negativity/progesterone receptor positivity v other ER positi vity), primary tumor size (< 2 cm v 2 to 5 cm v > 5 cm), site of relapse (l ocoregional v distant), disease-free interval (< 1.5 years v 1,5 to 3 years v > 3 years), adjuvant endocrine therapy (none v any), adjuvant chemothera py (none v any), and menopausal status (pre-, peri-, or postmenopausal). Results: Axillary lymph node status, site of relapse, and hormone receptor status were all highly significant as main effects in the model. After adju stment for other variables, disease-free interval alone was only modestly s ignificant but interacted with nodal status, After disease-free interval, h ormone receptor status, and site of relapse were accounted for, survival af ter relapse was poorer in node-positive cases, when compared with node-nega tive cases. The hazard ratios for patients with one to three and four or mo re involved nodes were 1.2 (95% confidence interval [CI], 0.8 to 1.9) and 2 .5 (95% CI, 1.8 to 3.4), respectively. Conclusion: Patients with four or more involved nodes at initial diagnosis have a significantly worse outcome after relapse than node-negative cases, regardless of the duration of the disease-free interval. We conclude that n odal metastasis is not only a marker of diagnosis at a later point in the n atural history of breast cancer but also a marker of an aggressive phenotyp e. (C) 1999 by American Society of Clinical Oncology.