Triple-negative breast cancer in Thai patients: Experience in King Chulalongkorn Memorial Hospital
Keywords:
Basal-like subtype, triple-negative breast cancer, ThaiAbstract
Background : Triple-negative breast cancer (TNBC) is defined by the lack of expression of ER, PR and Her-2 receptors and exhibits aggressive behaviors and poor clinical outcomes. Eighty percent of TNBCs are classified as basal-like tumor and share clinical behaviors that are consistent with this subtype of breast tumors.
Objectives : To characterize the epidemiological features of triple-negative breast cancers (TNBC) occurring in Thai patients in terms of demographics and pathological hallmarks including the expression patterns of ER, PR, Her-2, CK5/6, CK17 and EGFR as well as clinical outcomes.
Methods : In 166 TNBCs, adequate tissue samples were obtained from seventy cases, and patient/tumor characteristics as well as the survival outcomes were reviewed retrospectively.
Results : The mean age was 48.04 years (range 26 – 79 years); 89% of the tumors were invasive ductal carcinomas, and 72.4% were high-grade tumors. A high proliferative index (Ki-67 > 30%) was found in 81.4% of the samples. Positive staining for CK5/6 and CK17 were found in 51.4% and 55.7% of the tumors, respectively; 58.6% of the tumors had EGFR expression. After we analyzed the expressions of ER, HER-2, CK5/6 and EGFR to define the basal phenotype, 72.9% were categorized into the basal-like group. At a median of 67.5 months, 32.5% of the tumors recurred and 30.1% of the patients had died. The 5-year disease-free survival and overall survival estimates were 69% and 74%, respectively. In multivariate Cox proportional hazards models, the basal-like subtype was not independently correlated with DFS or OS in TNBCs (HR 1.72, [95% CI, 0.13 - 22.96], P = 0.68; for DFS and HR 2.34, [95% CI, 0.17 - 31.75], P = 0.52 for OS).
Conclusions : TNBCs occurred at younger age in these Thai patients than in previous studies. We also demonstrated higher tumor grades, higher proliferation indices and inferior outcomes of TNBCs in Thai patients. Additionally, the presence of basal-like characteristics was not an independent predictor of the survival outcome.
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References
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000;406:747-52. https://doi.org/10.1038/35021093
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001;98:10869-74. https://doi.org/10.1073/pnas.191367098
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 2003;100:8418-23.
https://doi.org/10.1073/pnas.0932692100
Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006;295: 2492-502.
https://doi.org/10.1001/jama.295.21.2492
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004; 10:5367-74.
https://doi.org/10.1158/1078-0432.CCR-04-0220
van de RM, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 2002;161:1991-6.
https://doi.org/10.1016/S0002-9440(10)64476-8
Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006; 19:264-71.
https://doi.org/10.1038/modpathol.3800528
Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F. p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch 2005; 447:688-94.
https://doi.org/10.1007/s00428-005-0010-7
Rakha EA, El Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer 2007; 109:25-32. https://doi.org/10.1002/cncr.22381
Korsching E, Packeisen J, Agelopoulos K, Eisenacher M, Voss R, Isola J, et al. Cytogenetic alterations and cytokeratin expression patterns in breast cancer: integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis. Lab Invest 2002;82: 1525-33.
https://doi.org/10.1097/01.LAB.0000038508.86221.B3
Won JR, Gao D, Chow C, Cheng J, Lau SY, Ellis MJ, et al. A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard. Mod Pathol 2013;26:1438-50. https://doi.org/10.1038/modpathol.2013.97
Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, et al. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Res 2007;9:R4.
https://doi.org/10.1186/bcr1636
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13: 4429-34.
https://doi.org/10.1158/1078-0432.CCR-06-3045
Harris LN, Broadwater G, Lin NU, Miron A, Schnitt SJ, Cowan D, et al. Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342. Breast Cancer Res 2006;8:R66. https://doi.org/10.1186/bcr1622
Tischkowitz M, Brunet JS, Begin LR, Huntsman DG, Cheang MC, Akslen LA, et al. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer 2007;7:134. https://doi.org/10.1186/1471-2407-7-134
Chuthapisith S, Permsapaya W, Warnnissorn M, Akewanlop C, Sirivatanauksorn V, Prasarttong OP. Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women. Asian Pac J Cancer Prev 2012;13:459-62. https://doi.org/10.7314/APJCP.2012.13.2.459
Lund MJ, Trivers KF, Porter PL, Coates RJ, Leyland-Jones B, Brawley OW, et al. Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat 2009;113: 357-70. https://doi.org/10.1007/s10549-008-9926-3
Yin WJ, Lu JS, Di GH, Lin YP, Zhou LH, Liu GY, et al. Clinicopathological features of the triple-negative tumors in Chinese breast cancer patients. Breast Cancer Res Treat 2009;115:325-33.
https://doi.org/10.1007/s10549-008-0096-0
Thike AA, Cheok PY, Jara-Lazaro AR, Tan B, Tan P, Tan PH. Triple-negative breast cancer: clinicopathological characteristics and relationship with basal-like breast cancer. Mod Pathol 2010;23:123-33. https://doi.org/10.1038/modpathol.2009.145
Iwase H, Kurebayashi J, Tsuda H, Ohta T, Kurosumi M, Miyamoto K, et al. Clinicopathological analyses of triple negative breast cancer using surveillance data from the Registration Committee of the Japanese Breast Cancer Society. Breast Cancer 2010; 17:118-24. https://doi.org/10.1007/s12282-009-0113-0
Rhee J, Han SW, Oh DY, Kim JH, Im SA, Han W, et al. The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer. BMC Cancer 2008;8:307.
https://doi.org/10.1186/1471-2407-8-307
Kanapathy Pillai SK, Tay A, Nair S, Leong CO. Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression in Malaysian women. BMC Clin Pathol 2012;12: 18.
https://doi.org/10.1186/1472-6890-12-18
Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, et al. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 2007; 9:R65. https://doi.org/10.1186/bcr1771
Choi YL, Oh E, Park S, Kim Y, Park YH, Song K, et al. Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival. BMC Cancer 2010;10:507.
https://doi.org/10.1186/1471-2407-10-507
Williams DJ, Cohen C, To TV, Page AJ, Lawson D, Sussman ZM, et al. Triple-negative breast carcinoma in women from Vietnam and the United States: characterization of differential marker expression by tissue microarray. Hum Pathol 2009;40:1176-81. https://doi.org/10.1016/j.humpath.2009.01.003
Pintens S, Neven P, Drijkoningen M, Van Belle V, Moerman P, Christiaens MR, et al. Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1. J Clin Pathol 2009;62:624-8.
https://doi.org/10.1136/jcp.2008.061358
Popovska SL, Ooi A, Ivanov IN, Ivanova NG,Dineva TB. Triple negative breast cancer does not fully overlap with basal-like molecular profile-A morphological and immunohistochemica study. J Biomed Clin Res 2010;3:45-50.
Rakha EA, Ellis IO. Triple-negative/basal-like breast cancer: review. Pathology 2009;41: 40-7.
https://doi.org/10.1080/00313020802563510
Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 2008;14: 1368-76. https://doi.org/10.1158/1078-0432.CCR-07-1658
Jumppanen M, Gruvberger-Saal S, Kauraniemi P, Tanner M, Bendahl PO, Lundin M, et al. Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers. Breast Cancer Res 2007;9: R16. https://doi.org/10.1186/bcr1649
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