Tumor Grade and Matrix Metalloproteinase 2 Expression in Stromal Fibroblasts Help to Stratify the High-Risk Group of Patients With Early Breast Cancer Identified on the Basis of St Gallen Recommendations

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Abstract

On the basis of an analysis performed with a group of 209 patients with chemotherapy-naive, early-stage, invasive, ductal breast cancer, it was found that high grade together with matrix metalloproteinase 2 negativity in stromal fibroblasts might be helpful in selecting poor survivors in the high-risk subgroup, ie, with luminal B, human epidermal growth factor receptor 2 overexpressing or triple-negative carcinoma.

Background:

It is still being discussed if the assessment of basal markers or if adhesion molecules expression contributes additional prognostic information to the classic prognostic factors and hence should be included into standard morphologic reports.

Patients and Methods:

The aim of the study was to assess the prognostic significance of: (i) classification recommended by St Gallen experts (ii) tumor grade, expression of (iii) basal markers, (iv) adhesion molecules, and (v) matrix metalloproteinase 2 (MMP-2) in patients with T1-T2 N0M0 chemotherapy-naive ductal breast cancer.

Results:

In 79 patients with tumors characterized by estrogen receptor (ER) and progesterone receptor (PgR) positive, human epidermal growth factor receptor 2 negative (HER2) phenotype and MIB-1 labeling index (MIB-l) LI ≤ 15% (low-risk group) cumulative 17-year breast cancer–specific survival probability was 100% and was significantly higher than in 95 patients from the high-risk group (ER−/PgR−/HER2− or HER2+ or MIB-1 LI > 15%) (72.5%). We found that MMP-2 fibroblast expression indicated 2 subgroups with significantly different survival rates in women with grade 3 tumor (88.9% for MMP-2 positivity and 56.0% for negativity). Cox multivariate analysis revealed that both grade 3 combined with stromal fibroblast MMP-2− and a high-risk group according to St Gallen recommendations are independent negative prognostic factors that influence survival of patients with breast cancer.

Conclusion:

To the best of our knowledge, we have shown for the first time that MMP-2− in stromal fibroblasts might indicate poor survivors in the group of patients with grade 3 tumors and that the cumulative effect of both above-mentioned parameters might be helpful in selecting the high-risk individuals from the group of patients with luminal B subtype/HER2+/triple negative phenotype identified according to St Gallen recommendations.

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