Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node-negative breast cancer patients

Abstract

Aims: To examine the importance of a fibrotic focus-a scar-like area in a carcinoma-as a marker of intratumoral hypoxia that correlates with angiogenesis and with clinical outcome in node-negative breast cancer.

Methods and results: One hundred and four T1-2N0M0 breast carcinoma patients were divided into two groups: group 1 (n=46) showing early distant relapse (median disease-free survival 25 months) and group 2 (n=58) showing no evidence of disease (median follow-up 91.5 months). All tumours were evaluated for medial/lateral location, size, histological grade, mitotic activity, necrosis, fibrotic focus, angiogenesis, vascular permeation and growth pattern. Multiple regression analysis showed that only histological grade and the presence of a fibrotic focus were independent predictors of early distant relapse. A fibrotic focus was present in 53% of the tumours. The relative size (fibrotic focus/tumour ratio) was significantly correlated with an unfavourable outcome. The presence of necrosis inside the fibrotic focus and the absolute and relative size of the fibrotic focus were significantly correlated with angiogenesis. A fibrotic focus was significantly associated with large, expansively growing tumours with high histological grade and numerous mitoses.

Conclusion: A fibrotic focus can be used as a surrogate for quantifying angiogenesis and is an independent predictor of early metastasis in lymph node-negative breast cancer.