HER2 expression estrogen and progesterone receptors and their relationship with clinicalpathological characteristics in Uruguayan patients with breast cancer
Keywords:
BREAST NEOPLASMS, RECEPTOR erbB-2, ESTROGEN RECEPTORS, PROGESTERONE RECEPTORSAbstract
Introduction: breast cancer, the main cause of death of Uruguayan women, is an heterogeneous disease. Study of the tumoral expression of the Human Epidermal growth factor Receptor-2 (HER2), the estrogen receptor and the progesterone receptor enables the recognition of sub-types with different clinical, and pathological characteristics and evolution.
Objectives: to learn about the HER2, estrogen receptor and progesterone receptor tumoral expression profile and their relationship with clinical-pathological characteristics in Uruguayan patients with breast cancer.
Method: we reviewed the medical record of patients who underwent surgery for invasive breast cancer within a two year period, and we selected those who had determination of estrogen receptor, progesterone receptor and HER2 through immune-histochemestry. We compared the expression profile of these markers with the age at the time of diagnosis, the histological type and degree and the pathological status.
Results: we selected 197 patients with the following characteristics: average age: 55 years old, ductal carcinoma: 85%, histological degree 1-2: 59%; stage I-II: 75%, axillary metastasis: 51%, progesterone receptor/estrogen receptors+ (RE/RP+): 78%, HER2+: 10%. Three subtypes were defined: HER2- RE/RP+ (73%), HER2+ (10%) and triple negative (TN) (17%). Subtypes TN and HER2+ were associated with a greater histological degree (GH) (p<0,05) and the TN with lower age at the time of diagnosis than the HER2-, RE/RP+ subtype.
Conclusions: the percentage of patients with HER2+ subtype invasive breast cancer (10%) is lower than the one reported in others studies. In accordance with previous studies, TN and HER2+ subtypes correlated with less differentiated tumors and TN subtype occurred in younger patients.
References
(2) Comisión Honoraria de Lucha contra el Cáncer. Programa Vigilancia Epidemiológica. Registro Nacional de Cáncer. Tendencias de la mortalidad por cáncer de mama en mujeres 2002-2005.
(3) Conzen SD, Grushko TA, Olopade OI. Cancer of the breast. In: Devita VT, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 8th ed. Philadelphia: Lippincott, 2008: 1595-605.
(4) Nielsen DL, Andersson M, Kamby C. HER2-targeted therapy in breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Cancer Treat Rev 2009; 35(2): 121-36.
(5) Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med 2009; 360(8): 790-800.
(6) van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347(25): 1999-2009.
(7) Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 2007; 356(3): 217-26.
(8) Sørlie T, Perou CM, Fan C, Geisler S, Aas T, Nobel A, et al. Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer. Mol Cancer Ther 2006; 5(11): 2914-8.
(9) 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(21): 2492-502.
(10) Dolled-Filhart M, Rydén L, Cregger M, Jirström K, Harigopal M, Camp RL, et al. Classification of breast cancer using genetic algorithms and tissue microarrays. Clin Cancer Res 2006; 12(21): 6459-68.
(11) Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sørlie T, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA 2005; 102(10): 3738-43.
(12) 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(14): 8418-23.
(13) Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000; 406(6797): 747-52.
(14) Huber KE, Carey LA, Wazer DE. Breast cancer molecular subtypes in patients with locally advanced disease: impact on prognosis, patterns of recurrence, and response to therapy. Semin Radiat Oncol 2009; 19(4): 204-10.
(15) Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 2009; 7(1-2): 4-13.
(16) Morales L, Reigosa A, Caleiras E, Mora R, Marrero N, Payares E, et al. Expresión del HER2/neu en pacientes venezolanas con cáncer de mama localmente avanzado. Invest Clin 2008; 49(1): 69-78.
(17) Colón E, Reyes JS, González Keelan C, Climent-Peris C. Prevalence of steroid receptors and HER 2/neu in breast cancer biopsies of women living in Puerto Rico. P R Health J 2002; 21(4): 299-303.
(18) Crabtree BE, Neme YY, Rivera S, Olivares G. Receptores hormonales, HER-2/neu y p53 en pacientes con cáncer de mama. GAMO 2005; 4(2): 29-33.
(19) Brück P, Vilches Cisneros N, Ramos López E, Barboza Quintana O, Ancer Rodríguez J, Flores Gutiérrez JP. Expresión de Her2-neu en el adenocarcinoma ductal de la glándula mamaria: correlación con parámetros histopatológicos y expresión de receptores estrogénicos en pacientes mexicanas. Ginecol Obstet Mex 2006; 74(10): 516-22.
(20) Peredo R, Sastre G, Serrano J, Hunter Mellado R. Her-2/neu oncogene expression in Puerto Rican females with breast cancer. Cell Mol Biol (Noisy-le-grand) 2001; 47(6): 1025-32.
(21) Gouvêa AP, Milanezi F, Olson SJ, Leitao D, Schmitt FC, Gobbi H. Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas. Appl Immunohistochem Mol Morphol 2006; 14(1): 103-8.
(22) González-Muller. Características patológicas asociadas al carcinoma de mama HER-2 positivo. An Fac Med Lima 2005; 66(2): 89-99.
(24) Álvarez Goyanes R, Escobar Pérez X, Camacho Rodríguez R, Franco Odio S, de Armas Fernández M, Ropero Toirac R, et al. Prevalencia de HER2 en el cáncer de mama en Cuba. Cancerología 2009; 4: 135-41.
(25) Fernandes RC, Bevilacqua JL, Soares IC, Siqueira SA, Pires L, Hegg R, et al. Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas. Histopathology 2009; 55(3): 346-52.
(26) American Joint Committee on Cancer. AJCC Cancer Staging Manual. 6th ed. New York: Springer, 2002.
(27) Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 2007; 109(9): 1721-8.
(28) Parise CA, Bauer KR, Brown MM, Caggiano V. Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999-2004. Breast J 2009; 15(6): 593-602.
(29) Kwan ML, Kushi LH, Weltzien E, Maring B, Kutner SE, Fulton RS, et al. Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 2009; 11(3): R31.
(30) Artagaveytia N. Alteraciones moleculares vinculadas al proceso de transformación maligna de la glándula mamaria: Implicancias en la evolución clínica del cáncer mamario. 2006. Tesis de Doctorado de ProInBio.
(31) Sabini G, Delgado L, Suárez L, Musé IM. Cáncer de mama localizado. In: Musé IM, Viola A, Sabini G, eds. Aspectos prácticos de la Clínica Oncológica. Montevideo: Sudamericana, 2004: 235-50.
(32) Vázquez T, Krygier G, Barrios E, Cataldi S, Vázquez A, Alonso R, et al. Análisis de sobrevida de una población con cáncer de mama y su relación con factores pronósticos: estudio de 1.311 pacientes seguidas durante 230 meses. Rev Med Urug 2005; 21(2): 107-21.
(33) Press MF, Sauter G, Bernstein L, Villalobos IE, Mirlacher M, Zhou JY, et al. Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res 2005; 11(18): 6598-607.
(34) Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007; 25(1): 118-45.