Fibrotic focus in breast carcinomas: relationship with prognostic parameters and biomarkers.

Background: Fibrotic focus (FF) has been observed in breast cancers and is suggested to be an important prognostic marker. However, most of these observations were reported by the same group of investigators with similar sample cohort. The relationship of FF and molecular subtypes as well as its associated prognosis has not been elucidated.

Methods: In this study, 450 cases of breast carcinomas were evaluated for the presence of FF and its association with clinicopathologic parameters and biomarkers.

Results: FF was found in 18.7% of all consecutive cases. FF was associated positively with infiltrative margins (p=0.03) but negatively with extensive in situ component (p<0.001) and lymphocytic infiltration (p<0.001). It was positively associated with estrogen receptor (p=0.007) but negatively with human epidermal growth factor receptor 2 (HER2; p=0.001), epidermal growth factor receptor (p=0.021), Ki-67 (p=0.001), and c-kit (p=0.009). Concomitantly, FF was seen more commonly in luminal A cancers (p<0.001) but less so in luminal B (p=0.045) and HER2-overexpressing cancers (p=0.011). Analysis on patient outcome (median 41 months, range 1-69 months) indicated that FF was an independent poor prognostic factor for disease-free survival (hazard ratio=2.57; 95% confidence interval=1.267-5.214, p=0.009), particularly in the luminal B subtype.

Conclusions: The findings suggested that FF is associated with specific tumor morphology of an infiltrative, stellate pattern (typical invasive ductal carcinoma-not otherwise specified) rather than round, cellular mass with intense lymphocytic infiltrate (basal-like breast cancers). The poor prognostic implication of FF is additional and independent of other adverse prognostic indicators.