Breast cancer and the stromal factor. The "prometastatic healing process" hypothesis

The correlation between axillary status and several histological features of breast carcinomas has been well established, however stromal changes have rarely been analyzed. Detailed clinicopathological review of 1803 patients with infiltrating breast carcinoma was performed. Stromal myxoid changes (SMC), size (T2-T3: > 2 cm, T1c: 1-2 cm, T1 a-b: < 1cm), fibrotic focus, age, lymphovascular embolizations, tumor infiltrating lymphocytes (TIL), multifocality, histological grade (G), estrogen receptors (ER), progesterone receptors (PR) and HER2 were semi-quantitated in two or three grades and correlated to axillary status. SMC3 followed by T2-T3, G3, fibrotic focus, T1c, embolizations, SMC2, TIL2, G2 and multifocality were strongly associated with positive axillary nodes; an inverse association was found with ER+++ and PR+++. Our findings support a critical role of the peritumoral stroma in the development of metastases. These stromal alterations should be remarked in routine pathology reports as they can be easily assessed and provide important information about tumor biology and aggressiveness. They could also become, in a future, the target of novel therapeutics.