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

Abstract

Early distant relapse occurs in a minority of node-negative breast cancer patients. Whether this poor prognosis can be predicted by the features of the primary tumour, or by the presence of occult metastases in the "negative" lymph nodes (LNs), remains a matter of debate. One hundred and four T(1-2)N(0)M(0) breast carcinoma patients were divided into two groups: group 1 (44%) showing early distant relapse with a median disease-free survival of 25 months, and group 2 (56%) showing no evidence of disease after a median follow-up of 91.5 months. All patients had received locoregional treatment only. All tumours were evaluated for medial/lateral location, histological type, size, grade, mitotic activity, fibrotic focus, necrosis, angiogenesis, growth pattern, and lymphatic vessel permeation. The haematoxylin and eosin-stained slides of all axillary LNs were revised and two additional levels were cut from each paraffin block for cytokeratin immunohistochemistry. In 24 patients (23%), occult metastases were found. These consisted of single cells or small clusters (SCs) in the marginal sinus in 17 patients (16%) and of larger colonies of cells in seven patients (7%). All detected metastases were 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 metastatic disease was significantly correlated with larger tumour size (p=0.02), higher histological grade (p=0.0008), mitotic activity (p<0.0001), presence of necrosis (p=0.0004), presence of fibrotic foci (p=0.0005), angiogenesis (p=0.0009), and lymphatic vessel permeation (p=0.018). Multiple logistic regression analysis showed that histological grade and the presence of a fibrotic focus were the only independent prognostic factors and that the presence of occult LN metastases was inversely correlated with early distant relapse. Prospective prognostic studies of occult LN metastases should consider the features of the primary tumour in a multivariate analysis.

Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity

“…Large central necrosis or fibrosis have also been reported to correlate with poor prognosis in early breast cancer [43], and to be strongly associated with basal-like [44] and ER-negative breast cancer [45]. Information on their prognostic value within the subgroup of triple-negative IDC is, however, lacking.…”

The relevance of occult axillary micrometastasis in ductal carcinoma in situ

“…2 However, the biologic potential of a tumor may also depend on other factors, including primary tumor size/volume, histologic and nuclear grades, lymphovascular invasion, and tumor necrosis/fibrosis. 4 All these features may in some way work to enhance partially or prominently the ability of a neoplasm to survive and proliferate at a secondary site. For these reasons, we have come to appreciate the need for accurate, consistent pathologic assessment of tumor size, histologic and nuclear grade, stromal angiogenesis, and local as well as distant metastais.…”

“…Some studies have suggested that histologic grade and, sometimes, the size of the tumor predict more accurately disease recurrence. 4 Although these findings are more applicable to invasive carcinomas, it has long been known that certain types and higher grades of DCIS have a greater propensity for disease recurrence. 2 The current study supports the findings of earlier studies that concluded that microscopic tumor deposition does not have significant clinical implications, especially if visualized by IHC only.…”

“…Regression analysis studies have identified several, potentially responsible features, such as tumor size, distance of surgical resection margins, hormone receptor status, and axillary lymph node involvement. 3,4 Axillary lymph node status has long been believed to be not only an indicator of prognosis, but a reason to recommend additional therapy. 5 The presence of tumor deposits in axillary lymph nodes, detected routinely by a single microscopic section stained with hematoxylin and eosin (H & E), has been shown to be a harbinger of more to expect.…”

“…7,8 Prognostic differences have been reported between these two groups. 3,4,9,10 Although there is a direct correlation between tumor size and incidence of positive axillary lymph nodes in invasive carcinomas, in DCIS (defined as tumor confined to the basement membrane and theoretically not invasive), axillary lymph nodes are positive 1-2% of the time and of questionable significance. 11,12 These metastases have been attributed to various factors, including the failure to identify a small invasive component and the histologically subtle loss of a restricting basement membrane, a phenomenon usually associated with high-grade intraductal lesions.…”