Breast 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. From 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). Of 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). HGF 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.

中文翻译：

---

原发肿瘤中肝细胞生长因子的高表达预示着男性乳腺癌更好的总体生存率

乳腺癌在男性中很少见，但治疗的重点是女性乳腺癌中常见的肿瘤特征。男性乳腺癌的肿瘤微环境尚不清楚，深入了解可能会改善男性乳腺癌的治疗。肝细胞生长因子 (HGF)/c-MET 轴和基质细胞衍生因子 1 (CXCL12)/CXC 趋化因子受体 4 型 (CXCR4) 轴可预测女性乳腺癌的预后。我们的目的是研究男性乳腺癌的这些因素，并将它们与患者的生存率联系起来。从参加 EORTC 10085/TBCRC/BIG/NABCG 国际男性乳腺癌计划 (NCT01101425) 并在 1990 年至 2010 年间诊断的 841 名荷兰乳腺癌男性中，收集了档案原发肿瘤样本。每个样品构建 3 个核心的组织微阵列，用于 HGF、c-MET、CXCL12 和 CXCR4 的免疫组织化学分析。使用Kaplan-Meier法分析无转移患者（M0）的总生存期（OS）。OS 相关标志物的值通过单变量和多变量 Cox 回归分析确定，提供风险比 (HR) 和 95% 置信区间 (95% CI)。841 名患者中的 720 名有足够的组织可供分析；720 名患者中有 487 名患有 M0 疾病。高 HGF 表达和高 CXCL12 表达的患者具有优越的 OS（两种标志物低表达 vs 高表达，7.5 年 vs 13.0 年，风险比 [HR] 0.64，95% CI 0.49–0.84，P = 0.001 [HGF]；9.1 vs 15.3 岁，HR 0.63，95% CI 0.45–0.87，P = 0.005 [CXCL12]）。多变量分析确定 HGF 是 OS 的独立预测因子（HR 0.64，95% CI 0.47–0.88，P = 0.001）。HGF 和 CXCL12 肿瘤表达似乎可以识别预后相对较好的男性乳腺癌患者。这可能会支持未来针对男性乳腺癌的特定管理策略。