Early distant relapse in 'node-negative' breast cancer patients is not predicted by occult axillary lymph node metastases, but by the features of theprimary tumour

Early distant relapse occurs in a minority of node-negative breast cancer p atients. Whether this poor prognosis can be predicted by the features of th e primary tumour, or by the presence of occult metastases in the 'negative' lymph nodes (LNs), remains a matter of debate. One hundred and four T1-2N0 M0 breast carcinoma patients were divided into two groups: group 1 (44%) sh owing early distant relapse with a median disease-free survival of 25 month s, and group 2 (56%) showing no evidence of disease after a median follow-u p of 91.5 months. All patients had received locoregional treatment only. Al l tumours were evaluated for medial/lateral location, histological type, si ze, grade, mitotic activity, fibrotic focus, necrosis, angiogenesis, growth pattern, and lymphatic vessel permeation. The haematoxylin and eosin-stain ed slides of all axillary LNs were revised and two additional levels were c ut from each paraffin block for cytokeratin immunohistochemistry. In 24 pat ients (23%), occult metastases were found. These consisted of single cells or small clusters (SCs) in the marginal sinus in 17 patients (16%) and of l arger colonies of cells in seven patients (7%). All detected metastases wer e smaller than 2 mm in diameter (micrometastases), There was no significant correlation between the presence of occult LN metastases (SCs or colonies) and the prognostically important features of the primary tumour. Early met astatic disease was significantly correlated with larger tumour size (p=0.0 2), higher histological grade (p=0.0008), mitotic activity (p<0.0001), pres ence of necrosis (p=0.0004), presence of fibrotic foci (p=0.0005), angiogen esis (p=0.0009), and lymphatic vessel permeation (p=0.018). Multiple logist ic regression analysis showed that histological grade and the presence of a fibrotic focus were the only independent prognostic factors and that the p resence of occult LN metastases was inversely correlated with early distant relapse. Prospective prognostic studies of occult LN metastases should con sider the features of the primary tumour in a multivariate analysis. Copyri ght (C) 2001 John Wiley & Sons, Ltd.