Cytoplasmic DDX3 as prognosticator in male breast cancer

Carmen C Van Der Pol,Cathy B Moelans,Elsken Van Der Wall,Marilot C T Batenburg,Lenny Verkooijen,Quirine F Manson,Inne Borel Rinkes,Paul J Van Diest,Venu Raman

doi:10.1007/s00428-021-03107-4

Abstract

Male breast cancer (MBC) is a rare disease. Due to its rarity, treatment is still directed by data mainly extrapolated from female breast cancer (FBC) treatment, despite the fact that it has recently become clear that MBC has its own molecular characteristics. DDX3 is a RNA helicase with tumor suppressor and oncogenic potential that was described as a prognosticator in FBC and can be targeted by small molecule inhibitors of DDX3. The aim of this study was to evaluate if DDX3 is a useful prognosticator for MBC patients. Nuclear as well as cytoplasmic DDX3 expression was studied by immunohistochemistry in a Dutch retrospective cohort of 106 MBC patients. Differences in 10-year survival by DDX3 expression were analyzed using log-rank test. The association between clinicopathologic variables, DDX3 expression, and survival was tested in uni- and multivariate Cox-regression analysis. High cytoplasmic DDX3 was associated with high androgen receptor (AR) expression while low nuclear DDX3 was associated with negative lymph node status. Nuclear and cytoplasmic DDX3 were not associated with each other. In a univariate analysis, high cytoplasmic DDX3 (p = 0.045) was significantly associated with better 10-year overall survival. In multivariate analyses, cytoplasmic DDX3 had independent prognostic value (p = 0.017). In conclusion, cytoplasmic DDX3 expression seems to be a useful prognosticator in MBC, as high cytoplasmic DDX3 indicated better 10-year survival.

Highlights

Male breast cancer (MBC) is a rare disease
Rarity, the treatment and prediction of MBC is still directed by data that are mainly extrapolated from randomized prospective studies or clinical experience of female breast cancer (FBC) treatment, despite the fact that during the last decade more and more has become known about the unique tumor biology of MBC [1,2,3,4,5].Nowadays, the focus in oncology is to prevent overtreatment and gain quality of life while maintaining survival rates
Grade, according to the modified Bloom and Richardson score [27], Mitotic Activity Index (MAI), histologic subtype, Ki67, androgen (AR), estrogen (ER; positive > = 1%) [28] and progesterone receptor (PR; positive > = 10%) and human epidermal growth factor receptor 2 (HER2) status were obtained from previous studies [2, 3, 29, 30]

Summary

Introduction

Male breast cancer (MBC) is a rare disease. Less than 1% of all male cancer patients have breast cancer and males account for less than 1% of all breast cancers [1]. The treatment and prediction of MBC is still directed by data that are mainly extrapolated from randomized prospective studies or clinical experience of female breast cancer (FBC) treatment, despite the fact that during the last decade more and more has become known about the unique tumor biology of MBC [1,2,3,4,5].Nowadays, the focus in oncology is to prevent overtreatment and gain quality of life while maintaining survival rates. The average age of male patients diagnosed with breast cancer is around 65 years, compared to 55 for female patients [4, 6,7,8]. The side effects of hormonal therapy in males are significant. If enhanced survival can be predicted, better decisions can be made for personalized chemo- and hormonal therapy

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Results