High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer
Tóm tắt
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.
Tài liệu tham khảo
Giordano SH. Breast cancer in men. N Engl J Med. 2018;378:2311–20.
Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol. 2013;24:1434–43.
Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN. Breast carcinoma in men: a population-based study. Cancer. 2004;101:51–7.
Sirieix J, Fraisse J, Mathoulin-Pelissier S, Leheurteur M, Vanlemmens L, Jouannaud C, et al. Management and outcome of metastatic breast cancer in men in the national multicenter observational ESME program. Ann Oncol. 2018;29 Abstract 294PD_PR.
Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol. 2010;28:232–9.
Liu N, Johnson KJ, Ma CX. Male breast cancer: an updated surveillance, epidemiology, and end results data analysis. Clin Breast Cancer. 2018;18:e997–1002.
Miao H, Verkooijen HM, Chia KS, Bouchardy C, Pukkala E, Larønningen S, et al. Incidence and outcome of male breast cancer: an international population-based study. J Clin Oncol. 2011;29:4381–6.
Kornegoor R, van Diest PJ, Buerger H, Korsching E. Tracing differences between male and female breast cancer: both diseases own a different biology. Histopathology. 2015;67:888–97.
Manson QF, Hoeve ND, Buerger H, Moelans CB, van Diest PJ. PD-1 and PD-L1 expression in male breast cancer in comparison with female breast cancer. Target Oncol. 2018;13:769–77.
Massarweh SA, Sledge GW, Miller DP, Mccullough D, Petkov VI. Molecular characterization and mortality from breast cancer in men. J Clin Oncol. 2018;36:1396–404.
Ottini L. Male breast cancer: a rare disease that might uncover underlying pathways of breast cancer. Nat Rev Cancer. 2014;14:643–4.
Bendinelli P, Maroni P, Matteucci E, Desiderio MA. Epigenetic regulation of HGF/Met receptor axis is critical for the outgrowth of bone metastasis from breast carcinoma. Cell Death Dis. 2017;8:e2578.
Domanska UM, Kruizinga RC, Nagengast WB, Timmer-Bosscha H, Huls G, de Vries EGE, et al. A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur J Cancer. 2013;49:219–30.
Ho-Yen CM, Jones JL, Kermorgant S. The clinical and functional significance of c-Met in breast cancer: a review. Breast Cancer Res. 2015;17:52.
Parr C, Ali AY. Boswellia frereana suppresses HGF-mediated breast cancer cell invasion and migration through inhibition of c-Met signalling. J Transl Med. 2018;12:281.
Zhao X, Qu J, Hui Y, Zhang H, Sun Y, Liu X, et al. Clinicopathological and prognostic significance of c-Met overexpression in breast cancer. Oncotarget. 2017;8:56758–67.
Garcia S, Dalès JP, Charafe-Jauffret E, Carpentier-Meunier S, Andrac-Meyer L, Jacquemier J, et al. Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype. Hum Pathol. 2007;38:830–41.
Edakuni G, Sasatomi E, Satoh T, Tokunaga O, Miyazaki K. Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma. Pathol Int. 2001;51:172–8.
Yang H, Zhang C, Cui S. Expression of hepatocyte growth factor in breast cancer and its effect on prognosis and sensitivity to chemotherapy. Mol Med Rep. 2015;11:1037–42.
Okuyama Kishima M, De Oliveira CEC, Banin-Hirata BK, Losi-Guembarovski R, Brajão De Oliveira K, Amarante MK, et al. Immunohistochemical expression of CXCR4 on breast cancer and its clinical significance. Anal Cell Pathol. 2015;2015:891020.
Pernas S, Martin M, Kaufman PA, Gil-Martin M, Gomez Pardo P, Lopez-Tarruella S, et al. Balixafortide plus eribulin in HER2-negative metastatic breast cancer: a phase 1, single-arm, dose-escalation trial. Lancet Oncol. 2018;19:812–24.
Rayson D, Lupichuk S, Potvin K, Dent S, Shenkier T, Dhesy-Thind S, et al. Canadian Cancer Trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative recurrent or metastatic breast cancer. Breast Cancer Res Treat. 2016;157:109–16.
Tolaney SM, Nechushtan H, Ron IG, Schöffski P, Awada A, Yasenchak CA, et al. Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Breast Cancer Res Treat. 2016;160:305–12.
Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, et al. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Investig New Drugs. 2015;33:1108–14.
Vermeulen MA, Slaets L, Cardoso F, Giordano SH, Tryfonidis K, van Diest PJ, et al. Pathological characterisation of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Eur J Cancer. 2017;82:219–27.
Cardoso F, Bartlett JMS, Slaets L, van Deurzen CHM, van Leeuwen-Stok E, Porter P, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018;29:405–17.
van der Vegt B, De Bock GH, Bart J, Zwartjes NG, Wesseling J. Validation of the 4B5 rabbit monoclonal antibody in determining Her2/neu status in breast cancer. Mod Pathol. 2009;22:879–86.
Matte I, Lane D, Laplante C, Garde-Granger P, Rancourt C, Piché A. Ovarian cancer ascites enhance the migration of patient-derived peritoneal mesothelial cells via cMet pathway through HGF-dependent and -independent mechanisms. Int J Cancer. 2015;137:289–98.
Han Z, Xiao Y, Wang K, Yan J, Xiao Z, Fang F, et al. Development of a SPECT tracer to image c-Met expression in a xenograft model of non-small cell lung cancer. J Nucl Med. 2018;59:1686–91.
Dmitriev P, Kiseleva E, Kharchenko O, Ivashkin E, Pichugin A, Dessen P, et al. Dux4 controls migration of mesenchymal stem cells through the Cxcr4-Sdf1 axis. Oncotarget. 2016;7:65090–108.
Zhang Y, Yang P, Sun T, Li D, Xu X, Rui Y, et al. MiR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis. Nat Cell Biol. 2013;15:284–94.
Yamashita J, Ogawa M, Yamashita S, Nomura K, Kuramoto M, Saishoji T, et al. Immunoreactive hepatocyte growth factor is a strong and independent predictor of recurrence and survival in human breast cancer. Cancer Res. 1994;54:1630–3.
Mirisola V, Zuccarino A, Bachmeier BE, Sormani MP, Falter J, Nerlich A, et al. CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival. Eur J Cancer. 2009;45:2579–87.
Kobayashi T, Tsuda H, Moriya T, Yamasaki T, Kikuchi R, Ueda S, et al. Expression pattern of stromal cell-derived factor-1 chemokine in invasive breast cancer is correlated with estrogen receptor status and patient prognosis. Breast Cancer Res Treat. 2010;123:733–45.
Liu H, Li Z, Deng M, Liu Q, Zhang T, Guo W, et al. Prognostic and clinicopathological value of CXCL12/SDF1 expression in breast cancer: a meta-analysis. Clin Chim Acta. 2018;484:72–80.
Moelans CB, de Ligt J, van der Groep P, Prins P, Besselink NJ, Hoogstraat M, et al. The molecular genetic make-up of male breast cancer. Endocr Relat Cancer. 2019;26:779–94.
Mavrogonatou E, Pratsinis H, Kletsas D. The role of senescence in cancer development. Semin Cancer Biol. 2019;S1044-579X:30127–0.