P5-14-14: The Presence of a Fibrotic Focus Adds Significant Prognostic Information to the Prognostic 76-Gene Relapse Score in Lymph Node Negative Breast Cancer.
Authors: Van den Eynden GG , Van Laere SJ , Smid M , Martens JW , Foekens JA , Vermeulen PB , Dirix LY 
Published: June 2012

Introduction: The fibrotic focus (FF) is a practical, easily assessable and reproducible integrative histological prognostic parameter in breast cancer. Its prognostic value has been shown before (Van den Eynden et al. Histopathology 2007). In this study we investigated whether the assessment of the FF adds prognostic information to the relapse score based on gene expression analysis of 76 genes as previously described (Wang et al. Lancet 2005).

Materials and Methods: All patients of 2 previous prognostic breast cancer gene expression studies for whom FFPE slides of the tumor were available (Wang et al. Lancet 2005 and Yu et al. BMC Cancer 2007) were selected, leading to a study population of 176 lymph node negative breast cancer patients. The presence and size (&lt;1/3 or &gt;1/3 of tumor area) of a FF were assessed on standard HE slides. These data were compared to the 76-gene relapse score, to standard clinicopathological variables and to metastasis-free survival.

Results: A small and large FF were found in 31 (17.6%) and 20 (11.4%) of patients, respectively. In 120 (68.2%) patients there was no FF and in 5 patients the presence of a FF could not be assessed due to insufficient FFPE material. 64 (36.4%) and 112 (63.6%) patients had respectively a good and poor prognostic 76-gene relapse score. There was a significant correlation between the presence of a FF and a poor 76-gene relapse score, 18 of 20 patients with a large FF had a poor relapse score (p = 0.03). Patients with a tumor with a FF and especially with a large FF had a significantly reduced metastasis free survival (Log rank p&lt;0.001). The same was true for patients with a poor 76-gene relapse score (Log rank p&lt;0.001). When only patients with a poor relapse score were taken into account, patients with a tumor with a large FF had a significantly decreased metastasis-free survival compared to patients without a FF or with a small FF (Log rank p=0.005). In patients with a good relapse score, the number of patients with a FF was too small for a separate analysis. In a multivariate Cox regression model for metastasis-free survival including age, ER and PR status, T stage, the FF and the 76-gene relapse score status, the FF (OR 1.5, p=0.02) and the relapse score status (OR 3.4, p = 0.001) were significant independent prognostic factors. Comparable results were found if the presence of a FF was dichotomized in large FF versus no or a small FF.

Conclusion: The assessment of the presence and size of a FF adds independent significant prognostic information to the prognostic 76-gene expression signature, especially in selecting a subgroup of patients with a very poor prognosis. Since the assessment of the FF is practical, easy, reproducible and cheap it should be considered to become part of the standard pathological examination of breast cancer resection specimens.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-14.