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

Aims: To examine the importance of a fibrotic focus-a scar-like area in a c arcinoma-as a marker of intratumoral hypoxia that correlates with angiogene sis and with clinical outcome in node-negative breast cancer. Methods and results: one hundred and four T1-2N0M0, breast carcinoma patien ts were divided into two groups: group 1 (n = 46) showing early distant rel apse median disease-free survival 25 months) and group 2 (n = 58) showing n o evidence of disease (median follow-up 91.5 months). All tumours were eval uated for medial/lateral location, size. histological grade, mitotic activi ty. necrosis. fibrotic focus. angiogenesis, vascular permeation and growth pattern. Multiple regression analysis showed that only histological grade a nd the presence of a fibrotic focus were independent predictors of early di stant relapse, A fibrotic focus was present in 53% of the tumours. The rela tive size (fibrotic focus/tumour ratio) was significantly correlated with a n 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 associate d with large, expansively growing tumours with high histological grade and numerous mitoses. Conclusion: A fibrotic focus can be used as a surrogate for quantifying ang iogenesis and is an independent predictor of early metastasis in lymph node -negative breast cancer.