High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer

Si-Qi Qiu,Hetty Timmer-Bosscha,Elisabeth G E De Vries,Bert Van Der Vegt,Hilde H Nienhuis,Geertruida H De Bock,Elise Van Leeuwen-Stok,Johan Van Rooijen,Annemiek M E Walenkamp,Carolien P Schröder,Carolien H M Van Deurzen

doi:10.1186/s13058-020-01266-x

Abstract

BackgroundBreast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. The tumor microenvironment of male breast cancer is less well understood, and insight may improve male breast cancer management. The hepatocyte growth factor (HGF)/c-MET axis and the stromal cell-derived factor-1 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis are prognostic in women with breast cancer. We aimed to investigate these factors in male breast cancer and correlate them with patient survival.MethodsFrom 841 Dutch males with breast cancer who were enrolled in the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program (NCT01101425) and diagnosed between 1990 and 2010, archival primary tumor samples were collected. Tissue microarrays were constructed with 3 cores per sample and used for immunohistochemical analysis of HGF, c-MET, CXCL12, and CXCR4. Overall survival (OS) of the patients without metastases (M0) was analyzed using the Kaplan-Meier method. The value of the markers regarding OS was determined using univariable and multivariable Cox regression analyses, providing hazard ratios (HRs) and 95% confidence intervals (95% CIs).ResultsOf 720 out of 841 patients, sufficient tissue was available for analysis; 487 out of 720 patients had M0 disease. Patients with high HGF expression and high CXCL12 expression had a superior OS (low vs high expression of both markers, 7.5 vs 13.0 years, hazard ratio [HR] 0.64, 95% CI 0.49–0.84, P = 0.001 [HGF]; 9.1 vs 15.3 years, HR 0.63, 95% CI 0.45–0.87, P = 0.005 [CXCL12]). Multivariate analysis identified HGF as an independent predictor for OS (HR 0.64, 95% CI 0.47–0.88, P = 0.001).ConclusionsHGF and CXCL12 tumor expression appear to identify male breast cancer patients with a relatively good prognosis. Possibly, this could support male breast cancer-specific management strategies in the future.

Highlights

Breast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer
Patient and tumor characteristics In 720 out of the 841 patients, sufficient tumor tissue was available for analysis (Fig. 1)
human epidermal growth factor receptor 2 (HER2) positivity was present in tumors of 31 patients (4.9%)

Summary

Introduction

Breast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. Male breast cancer has more favorable tumor characteristics than female breast cancer, such as lower tumor grade, a higher incidence of estrogen receptor (ER) expression, and a lower incidence of human epidermal growth factor receptor 2 (HER2) expression [1, 3]. The outcome in male breast cancer is similar compared to women after correction for age and stage, in general, survival improvement in men is still lagging behind [1, 4,5,6,7]. A better understanding of the breast tumor characteristics in men may help to improve treatment strategies for male breast cancer

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