Abstract

Simple SummaryBreast cancer is the most incident malignancy and the leading cause of oncological death among women. The recent advances in the treatment of this disease are due to the increasing ability to individualize therapy, in the so called “precision medicine” era. This approach is based on the knowledge of molecular and genetic features of the tumor. Therefore, there is a continuous search for new prognostic factors that may allow us to better stratify patients according to their individual risk. The most promising one seems to be the FGD3 gene expression, which has been shown to be prognostic in breast cancer: the aim of our study was to analyze the prognostic value of FGD3 expression by immunohistochemistry and to compare it with traditional factors. Immunohistochemistry is easy and cheap; to provide by its use a prognostic factor stronger than classical ones may greatly aid in the practical management of this disease.Among new prognostic factors for breast cancer, the most promising one seems to be FGD3 (Facio-Genital Dysplasia 3) gene, whose expression improves outcome by inhibiting cell migration. The aim of the study was to evaluate the prognostic role of FGD3 in invasive breast cancer in a series of 401 women, treated at our unit, by evaluating the expression of this gene by immunohistochemistry. Patients with high FGD3 expression showed a significantly better disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). The prognostic value of FGD3 expression was stronger than that of classical pathologic parameters such as histological grade of differentiation, Ki-67 index and molecular subtype. By multivariate Cox analysis, FGD3 expression was confirmed as significant and independent prognostic factor, ranking second after age at diagnosis (≤40 years) for DFS (p = 0.003) and the second strongest predictor of OS, after AJCC Stage (p < 0.001). Our data suggest that inclusion of FGD3 evaluation in the routine workup of breast cancer patients may result in a more accurate stratification of the individual risk. The possibility to assess FGD3 expression by a simple and cheap technique such as immunohistochemistry may enhance the spread of its use in the clinical practice.

Highlights

  • Breast cancer is the most frequent cancer among women, and its incidence shows an increasing trend, while its mortality is slightly decreasing, it is still the highest of all cancers in women

  • The current study confirms that Facio-Genital Dysplasia 3 gene (FGD3) expression is a significant and independent predictor of clinical outcome; in particular, high FGD3 expression was a protective factor against recurrence, death from disease and lymph node involvement

  • FGD3 expression allowed to distinguish within a group of patients with overlapping traditional prognostic assessment, those with a better clinical outcome

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Summary

Introduction

Breast cancer is the most frequent cancer among women, and its incidence shows an increasing trend, while its mortality is slightly decreasing, it is still the highest of all cancers in women. The advances in the number and efficacy of pharmacological protocols as well as the introduction of targeted biological treatments have led to a significant improvement in the prognosis of breast cancer. All these features resulted in a progressive reduction in mortality in recent years with a parallel increase in disease free survival (DFS) and overall survival (OS) [1]. It is not uncommon to observe that patients with similar prognostic features display different clinical outcomes For this reason, research is constantly ongoing to discover new prognostic factors that may allow us to better identify patients at higher risk for recurrence and death from disease

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