Análisis de sobrevida según perfil biológico de pacientes uruguayas con cáncer de mama

Cecilia Castillo; Natalia Camejo; Lucía Delgado; Rodrigo Fresco; Guianeya Santander; Sergio Aguiar; Valeria González; Silvina Heinzen; Gonzalo Spera; Luis Ubillos; Franco Xavier; Hugo Deneo; Marta Aghazarian; Robinson Rodríguez; Graciela Sabini

Authors

Cecilia Castillo Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Asistente
Natalia Camejo Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Ex Residente
Lucía Delgado Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica Profesor
Rodrigo Fresco Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Profesor Adjunto
Guianeya Santander Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Asistente
Sergio Aguiar Universidad de la República. Facultad de Medicina. Hospital de Clínicas, Servicio de Oncología Radioterápica. Ex Prof. Adjunto
Valeria González CASMU, Departamento de Oncología Clínica. Ex Residente
Silvina Heinzen Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Departamento Básico de Medicina. Asistente
Gonzalo Spera Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Ex Residente
Luis Ubillos Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Asistente
Franco Xavier Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Ex Residente
Hugo Deneo Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Cátedra de Anatomía Patológica. Prof. Agdo
Marta Aghazarian ASSE, Instituto Nacional del Cáncer, Departamento de Oncología Médica. Jefe
Robinson Rodríguez Hospital Central de las Fuerzas Armadas, Servicio de Oncología. Jefe
Graciela Sabini Universidad de la República, Facultad de Medicina, Hospital de Clínicas, Servicio de Oncología Clínica. Ex Prof. Directora

Keywords:

SURVIVAL ANALYSIS, PROGNOSIS, BREAST NEOPLASMS, STROGEN RECEPTORS, PROGESTERONE RECEPTORS, ErbB-2 RECEPTOR

Abstract

Introduction: breast cancer constitutes an heterogeneous disease. Two sub-types have been distinguished through the study of the tumor expression level of hormone receptors tumors, and level of HER2 expression, among other techniques. We previously reported the relation between these sub-types and the clinical and pathological characteristics of Uruguayan women.
Objective: to analyse the disease-free survival (DFS) of Uruguayan patients with breast cancer, according to their biological sub-type, defined based on the tumor expression of hormone receptors and HER2 expression which were assessed by immune-histological chemistry staining.
Method: all clinical records of patients who had undergone breast cancer surgery (Stages I-III) during a two year period were reviewed. The disease-free survival rate was calculated for all patients and according to their biological profile.
Results: forty months follow up revealed disease-free survival upon two years of 92.3% for all patients; 94% for hormone receptor positive /HER2 negative patients, 91% for triple negative patients, and 71.4% for hormone receptor positive patients.
Comparing the DFS curves, for the different sub-types, evidenced a lower DFS for HER2+ patients (p = 0.03), and similar DFS for hormone receptor positive/HER2 negative and triple negative (p = 0.86).
Conclusions: uruguayan patients with breast cancer show a two-year-DFS that matches international reports. HER2+ patients evidence a higher relapse rate, also consistent with international reports. Similar DFS upon two years, between hormone receptor positive/HER2 negative patients and triple negative patients cannot be due to differences in the clinical-pathological characteristics, thus a hypothesis is considered: there is a larger proportion of patients of the luminal B breast cancer sub-type among hormone receptor positive/HER2 negative patients.

References

(1) Barrios E, Vasallos JA, Alonso R, Garau M, Musetti C. III Atlas de incidencia del cáncer en el Uruguay 2002-2006. Montevideo: Comisión Honoraria de Lucha Contra el Cáncer, Registro Nacional de Cáncer, 2010.
(2) Barrios E, Vasallos JA, Alonso R, Garau M, Musetti C. IV Atlas de mortalidad por cáncer en el Uruguay 2004-2008. Montevideo: Comisión Honoraria de Lucha Contra el Cáncer, Registro Nacional de Cáncer, 2012. En prensa.
(3) Uruguay. Comisión Honoraria de Lucha Contra el Cáncer. Mortalidad en Uruguay 1990-2008: tendencias. Montevideo: CHLCC, 2009. p. 15. Disponible en: http://www.urucan.org.uy/uilayer/ve/Mortalidad_1990_2008_Tendencias.pdf Consulta: 29 noviembre 2011.
(4) 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.
(5) Sørlie 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 U S A 2001; 98(19):10869-74.
(6) Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010; 12(5):R68.
(7) 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.
(8) 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.
(9) Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 2007; 13(8):2329-34.
(10) Delgado L, Fresco R, Santander G, Aguiar S, Camejo N, Ferrero L, et al. Expresión tumoral de HER-2, receptores de estrógenos y de progesterona y su relación con características clínico-patológicas en pacientes uruguayas con cáncer de mama. Rev Med Urug 2010; 26(3):145-53.
(11) American Joint Committee on Cancer. AJCC Cancer Stading Manual. 7th ed. New York: Springer, 2010. p. 347-76.
(12) Harris JR, Lippman ME, Morrow M, Osborne CK. Enfermedades de la mama. 4 ed. Madrid: Lippincott Williams & Wilkins, 2011. Cap. 31, 48.
(13) Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353(16):1659-72.
(14) Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 2011; 12(3):236-44.
(15) Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab afteradjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369(9555):29-36.
(16) Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353(16):1673-84.
(17) Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 2011; 29(25):3366-73.
(18) Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Rolski J, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study. Proceedings of the San Antonio Breast Cancer Symposium 2005. Cancer Res 2009; 69(24 Suppl):abstract 62. Disponible en: http://www.bcirg.org/NR/rdonlyres/euynx4wi7wx6yq4qenuxw5ok6bbclmm5ckfz5vyo7kdkrbg5iq4ketb23g4epbwzpld5vhqbsiolga72y2itf7plpqb/BCIRG+006+-+Final+Abstract+SABCS.pdf. Consulta: 10 diciembre 2011.
(19) Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365(14):1273-83.
(20) Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006; 354(8):809-20.
(21) 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(15 Pt 1):4429-34.
(22) Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009; 101(10):736-50.
(23) Dignam JJ, Dukic V, Anderson SJ, Mamounas EP, Wickerham DL, Wolmark N. Hazard of recurrence and adjuvant treatment effects over time in lymph node-negative breast cancer. Breast Cancer Res Treat 2009; 116(3):595-602.
(24) Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 2009; 27(8):1323-33.