Predictores genéticos en cáncer mamario Importancia de la prueba de 21 genes para predecir la tasa de recurrencia y la indicación de la quimioterapia
Palabras clave:
neoplasias de la mama, pruebas genéticas, quimioterapia adyuvante, receptores estrogénicos, pronósticoResumen
El carcinoma mamario es el cáncer más frecuente en mujeres en todo el mundo. En Colombia es la neoplasia maligna más frecuente en las mujeres.
Aun cuando su incidencia ha aumentado en las últimas décadas, su mortalidad se ha reducido algo o ha per- manecido estable. A pesar de los progresos obtenidos en el manejo quirúrgico que permiten obtener resulta- dos similares con intervenciones menos mutiladoras, de las nuevas técnicas de radioterapia que producen menos efectos secundarios y de los avances en los tra- tamientos con quimioterapia, aún no tenemos la habili- dad de predecir qué pacientes van a tener recurrencias y quiénes se beneficiarán de la terapia adyuvante.
En el pasado nos hemos confiado en paradigmas esta- blecidos, tales como el tamaño y el grado tumoral, la edad de las pacientes, la presencia de receptores hormonales y el compromiso por el tumor de los ganglios linfáticos. Sin embargo, el descubrimiento de diferen- tes subtipos de cáncer mamario nos demuestra que el cáncer mamario no es una entidad única y, por lo tan- to, la terapia debe ser individualizada, pues es posible que en algunos casos el tratamiento usado no sea el mejor y en otros, tal vez, sea innecesario.
En este artículo se presentan varias de las pruebas genéticas disponibles, las que predicen las posibilida- des de recurrencia del tumor y determinan cuáles pa- cientes se pueden beneficiar con la quimioterapia y cuáles no se benefician.
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Referencias bibliográficas
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https://doi.org/10.1136/bmj.c3620
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https://doi.org/10.1016/j.ejca.2009.12.014
5. Urban JA, Baker HW. Radical mastectomy with in bloc resection of the internal mammary lymph node chain. Cancer. 1952;5:992.
https://doi.org/10.1002/1097-0142(195209)5:5<992::AID-CNCR2820050515>3.0.CO;2-Z
6. Urban JA. Clinical experience and results of excision of internal mammary lymph node chain in primary operable breast cancer. Cancer. 1959;12:14.
https://doi.org/10.1002/1097-0142(195901/02)12:1<14::AID-CNCR2820120106>3.0.CO;2-L
7. Cáceres E. Radical mastectomy with resection of internal mammary chain. Acta Union Intern Contre Cancrum. 1958;15:106.
8. Patiño JF. Historia de la mastectomía y estado actual del trata- miento del cáncer mamario. En: Patiño JF. Lecciones de ciru- gía. Bogotá: Editorial Médica Panamericana; 2001.
9. Fisher B, Bauer M, Margolese R, Poisson R, Pilch YL, Redmond C, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1985;312:665-73.
https://doi.org/10.1056/NEJM198503143121101
10. Fisher B, Redmond C, Fisher ER, Bauer M, Wolmark N, Wickerham L, et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med. 1985;312:674-81.
https://doi.org/10.1056/NEJM198503143121102
11. Crile G Jr. Rationale of simple mastectomy without radiation for stage I cancer of the breast. Surg Gynecol Obstet. 1965;120:975.o o1 he changing role o
12. Fisher B. The changing role of surgery in the treatment of cancer. In: Becker FF, editor. Cancer: A comprehensive treatise. New York: Plenum Publishing Comp.; 1977;401-21.
13. Veronesi U, Saccozzi R, Del Vecchio M, Banfi A, Clemente C, De Lena M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med. 1981;305:6-11.
https://doi.org/10.1056/NEJM198107023050102
14. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227-332.
https://doi.org/10.1056/NEJMoa020989
15. Patiño JF. Una visión actual sobre cirugía conservadora en cán- cer mamario. Revista Colombiana de Cirugía. 1989;4:57-62.
16.The START Trialists' Group. The UK Standardization of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: A randomized trial. Lancet Oncol. 2008;9:331-41.
https://doi.org/10.1016/S1470-2045(08)70077-9
17. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpiaet S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362:513-20.
https://doi.org/10.1056/NEJMoa0906260
18. Mackman S. Ramírez G, Ansfield FJ. Results of 5-fluorouracil (NSC-19893) given by the multiple daily dose method in disseminated breast cancer. Cancer Chemother Rep. 1967;51:483.
19. Canellos GP, Pocock SJ, Taylor S, Sears ME, Klaasen DJ, Band PR, et al. Combination chemotherapy for metastatic breast car- cinoma. Prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer. 1976;38:1882-6.
https://doi.org/10.1002/1097-0142(197611)38:5<1882::AID-CNCR2820380503>3.0.CO;2-H
20. Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005;353:1734-6.
https://doi.org/10.1056/NEJMe058196
21. Moreira C, Kaklamani V. Lapatinib and breast cancer: Current indications and outlook for the future. Expert Rev Anticancer Ther. 2010;10:1171-82.
https://doi.org/10.1586/era.10.113
22. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294:405-10.
https://doi.org/10.1056/NEJM197602192940801
23. Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, et al. Two months of doxorubicin- cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: Results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990;8:1483-96.
https://doi.org/10.1200/JCO.1990.8.9.1483
24. Early Breast Cancer Trialists' Collaborative Group. The effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: An overview of 61 randomized trials among 28,859 women. N Engl J Med. 1988;319:1681-92.
https://doi.org/10.1056/NEJM198812293192601
25. Adjuvanttherapyforbreastcancer.NIHConsensusDevelopment Conference, November 1-3, 2000, Program and Abstracts, Office of the Director, National Institutes of Health.
26. Goldhirsch A, Glick JH, Gelber RD, Coates AS, Senn HJ. Mee- ting highlights: International Consensus Panel on the treatment of primary breast cancer. J Clin Oncol. 2001;19:3817-27.
https://doi.org/10.1200/JCO.2001.19.18.3817
27. Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9:606-16.
https://doi.org/10.1634/theoncologist.9-6-606
28. Abaúnza H. Cáncer mamario. Factores pronósticos. Revista Colombiana de Cirugía. 1993;8:24-9.
29. Paik S, Tang G, Shak S, Kim C Baker J, Kim W, et al. Gene expression and benefit of chemo therapy in women with node- negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726-34.
https://doi.org/10.1200/JCO.2005.04.7985
30. Lønning PE. Breast cancer prognostication and prediction: Are we making progress? Ann Oncol. 2007;18(Suppl.8):3-7.
https://doi.org/10.1093/annonc/mdm260
31. Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001;19:980-91.
https://doi.org/10.1200/JCO.2001.19.4.980
32. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747-52.
https://doi.org/10.1038/35021093
33. Clinical implementation of the intrinsic subtypes of breast cancer. Lancet Oncol. 2010;11:718-9.
https://doi.org/10.1016/S1470-2045(10)70176-5
34. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, et al. Gene expression profiling in breast cancer: Understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98:262-72.
https://doi.org/10.1093/jnci/djj052
35. Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, et al. TRANSBIG Consortium. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13:3207-14.
https://doi.org/10.1158/1078-0432.CCR-06-2765
36. Chang HY, Sneddon JB, Alizadeh A, Sood R, West RB, Montgomery K, et al. Gene expression signature of fibroblast serum response predicts human cancer progression: Similarities between tumors and wounds. Biology. 2004;2:206-14.
https://doi.org/10.1371/journal.pbio.0020007
37. Ma XJ, Wang Z, Ryan PD, Isakoff SJ, Barmettler A, Fuller A, et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell. 2004;5:607- 16.
https://doi.org/10.1016/j.ccr.2004.05.015
38. van de Vijver MJ, He YD, van de Veer LJ, Dai H, Hart AA, Voskuil DW, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530-6.
https://doi.org/10.1038/415530a
39. Paik S, Shak S, Tang G, Chungyeul K, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817-26.
https://doi.org/10.1056/NEJMoa041588
40. Mamounas E, Tang G, Bryant J. Association between the 21- gene recurrence score assay (RS) and risk of locoregional failure in node-negative, ER-positive breast cancer: Results from NSABP B-14 and NSABP B-20. Proceedings from the 28th annual San Antonio Breast Cancer Symposium. San Antonio, Texas. December 8-11, 2005. Abstract # 29.
https://doi.org/10.1200/JCO.2009.23.7610
41. Badve SS, Baehner FL, Gray RP, Childs BH, Maddala T, Liu M-L, et al. Estrogen- and progesterone-receptor status in ECOG 2197: Comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory . J Clin Oncol. 2008;26:2473-81.
https://doi.org/10.1200/JCO.2007.13.6424
42. Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT; Breast Cancer Intergroup of North America. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen- receptor-positive breast cancer on chemotherapy: A retrospective analysis of a randomized trial. Lancet Oncol. 2010;11:55-65.
https://doi.org/10.1016/S1470-2045(09)70314-6
43. Asad J, Jacobson AF, Estabrook A, Smith SR, Boolbol SK, Feldman SM, et al. The American Society of Breast Surgeons. Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer? Am J Surg. 2008;196:527-9.
https://doi.org/10.1016/j.amjsurg.2008.06.021
44. Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, KashJ, et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol. 2010;28:1671-6.
https://doi.org/10.1200/JCO.2008.20.2119
45. Pruthi S, Brandt KR, Degnim AC, Goetz MP, Goetz MP, Pérez EA, et al. A multidisciplinary approach to the management of breast cancer. Part 1: Prevention and diagnosis. Mayo Clin Proc. 2007;82:999-1012.
https://doi.org/10.4065/82.8.999
2. Autier P, Boniol M, LaVecchia C, Vatten L, Gavin A, Héry C, et al. Disparities in breast cancer mortality trends between 30 European countries: Retrospective trend analysis of WHO mortality database. Br Med J. 2010;341:c3620.
https://doi.org/10.1136/bmj.c3620
3. Hernández G, Herrán S, Cantor LF. Análisis de las tendencias de mortalidad por cáncer de mama en Colombia y Bogotá, 1981- 2000. Revista Colombiana de Cancerología. 2007;11:32-9.
4. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765-81.
https://doi.org/10.1016/j.ejca.2009.12.014
5. Urban JA, Baker HW. Radical mastectomy with in bloc resection of the internal mammary lymph node chain. Cancer. 1952;5:992.
https://doi.org/10.1002/1097-0142(195209)5:5<992::AID-CNCR2820050515>3.0.CO;2-Z
6. Urban JA. Clinical experience and results of excision of internal mammary lymph node chain in primary operable breast cancer. Cancer. 1959;12:14.
https://doi.org/10.1002/1097-0142(195901/02)12:1<14::AID-CNCR2820120106>3.0.CO;2-L
7. Cáceres E. Radical mastectomy with resection of internal mammary chain. Acta Union Intern Contre Cancrum. 1958;15:106.
8. Patiño JF. Historia de la mastectomía y estado actual del trata- miento del cáncer mamario. En: Patiño JF. Lecciones de ciru- gía. Bogotá: Editorial Médica Panamericana; 2001.
9. Fisher B, Bauer M, Margolese R, Poisson R, Pilch YL, Redmond C, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1985;312:665-73.
https://doi.org/10.1056/NEJM198503143121101
10. Fisher B, Redmond C, Fisher ER, Bauer M, Wolmark N, Wickerham L, et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med. 1985;312:674-81.
https://doi.org/10.1056/NEJM198503143121102
11. Crile G Jr. Rationale of simple mastectomy without radiation for stage I cancer of the breast. Surg Gynecol Obstet. 1965;120:975.o o1 he changing role o
12. Fisher B. The changing role of surgery in the treatment of cancer. In: Becker FF, editor. Cancer: A comprehensive treatise. New York: Plenum Publishing Comp.; 1977;401-21.
13. Veronesi U, Saccozzi R, Del Vecchio M, Banfi A, Clemente C, De Lena M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med. 1981;305:6-11.
https://doi.org/10.1056/NEJM198107023050102
14. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227-332.
https://doi.org/10.1056/NEJMoa020989
15. Patiño JF. Una visión actual sobre cirugía conservadora en cán- cer mamario. Revista Colombiana de Cirugía. 1989;4:57-62.
16.The START Trialists' Group. The UK Standardization of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: A randomized trial. Lancet Oncol. 2008;9:331-41.
https://doi.org/10.1016/S1470-2045(08)70077-9
17. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpiaet S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362:513-20.
https://doi.org/10.1056/NEJMoa0906260
18. Mackman S. Ramírez G, Ansfield FJ. Results of 5-fluorouracil (NSC-19893) given by the multiple daily dose method in disseminated breast cancer. Cancer Chemother Rep. 1967;51:483.
19. Canellos GP, Pocock SJ, Taylor S, Sears ME, Klaasen DJ, Band PR, et al. Combination chemotherapy for metastatic breast car- cinoma. Prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer. 1976;38:1882-6.
https://doi.org/10.1002/1097-0142(197611)38:5<1882::AID-CNCR2820380503>3.0.CO;2-H
20. Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005;353:1734-6.
https://doi.org/10.1056/NEJMe058196
21. Moreira C, Kaklamani V. Lapatinib and breast cancer: Current indications and outlook for the future. Expert Rev Anticancer Ther. 2010;10:1171-82.
https://doi.org/10.1586/era.10.113
22. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294:405-10.
https://doi.org/10.1056/NEJM197602192940801
23. Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, et al. Two months of doxorubicin- cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: Results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990;8:1483-96.
https://doi.org/10.1200/JCO.1990.8.9.1483
24. Early Breast Cancer Trialists' Collaborative Group. The effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: An overview of 61 randomized trials among 28,859 women. N Engl J Med. 1988;319:1681-92.
https://doi.org/10.1056/NEJM198812293192601
25. Adjuvanttherapyforbreastcancer.NIHConsensusDevelopment Conference, November 1-3, 2000, Program and Abstracts, Office of the Director, National Institutes of Health.
26. Goldhirsch A, Glick JH, Gelber RD, Coates AS, Senn HJ. Mee- ting highlights: International Consensus Panel on the treatment of primary breast cancer. J Clin Oncol. 2001;19:3817-27.
https://doi.org/10.1200/JCO.2001.19.18.3817
27. Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9:606-16.
https://doi.org/10.1634/theoncologist.9-6-606
28. Abaúnza H. Cáncer mamario. Factores pronósticos. Revista Colombiana de Cirugía. 1993;8:24-9.
29. Paik S, Tang G, Shak S, Kim C Baker J, Kim W, et al. Gene expression and benefit of chemo therapy in women with node- negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726-34.
https://doi.org/10.1200/JCO.2005.04.7985
30. Lønning PE. Breast cancer prognostication and prediction: Are we making progress? Ann Oncol. 2007;18(Suppl.8):3-7.
https://doi.org/10.1093/annonc/mdm260
31. Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001;19:980-91.
https://doi.org/10.1200/JCO.2001.19.4.980
32. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747-52.
https://doi.org/10.1038/35021093
33. Clinical implementation of the intrinsic subtypes of breast cancer. Lancet Oncol. 2010;11:718-9.
https://doi.org/10.1016/S1470-2045(10)70176-5
34. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, et al. Gene expression profiling in breast cancer: Understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98:262-72.
https://doi.org/10.1093/jnci/djj052
35. Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, et al. TRANSBIG Consortium. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13:3207-14.
https://doi.org/10.1158/1078-0432.CCR-06-2765
36. Chang HY, Sneddon JB, Alizadeh A, Sood R, West RB, Montgomery K, et al. Gene expression signature of fibroblast serum response predicts human cancer progression: Similarities between tumors and wounds. Biology. 2004;2:206-14.
https://doi.org/10.1371/journal.pbio.0020007
37. Ma XJ, Wang Z, Ryan PD, Isakoff SJ, Barmettler A, Fuller A, et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell. 2004;5:607- 16.
https://doi.org/10.1016/j.ccr.2004.05.015
38. van de Vijver MJ, He YD, van de Veer LJ, Dai H, Hart AA, Voskuil DW, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530-6.
https://doi.org/10.1038/415530a
39. Paik S, Shak S, Tang G, Chungyeul K, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817-26.
https://doi.org/10.1056/NEJMoa041588
40. Mamounas E, Tang G, Bryant J. Association between the 21- gene recurrence score assay (RS) and risk of locoregional failure in node-negative, ER-positive breast cancer: Results from NSABP B-14 and NSABP B-20. Proceedings from the 28th annual San Antonio Breast Cancer Symposium. San Antonio, Texas. December 8-11, 2005. Abstract # 29.
https://doi.org/10.1200/JCO.2009.23.7610
41. Badve SS, Baehner FL, Gray RP, Childs BH, Maddala T, Liu M-L, et al. Estrogen- and progesterone-receptor status in ECOG 2197: Comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory . J Clin Oncol. 2008;26:2473-81.
https://doi.org/10.1200/JCO.2007.13.6424
42. Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT; Breast Cancer Intergroup of North America. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen- receptor-positive breast cancer on chemotherapy: A retrospective analysis of a randomized trial. Lancet Oncol. 2010;11:55-65.
https://doi.org/10.1016/S1470-2045(09)70314-6
43. Asad J, Jacobson AF, Estabrook A, Smith SR, Boolbol SK, Feldman SM, et al. The American Society of Breast Surgeons. Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer? Am J Surg. 2008;196:527-9.
https://doi.org/10.1016/j.amjsurg.2008.06.021
44. Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, KashJ, et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol. 2010;28:1671-6.
https://doi.org/10.1200/JCO.2008.20.2119
45. Pruthi S, Brandt KR, Degnim AC, Goetz MP, Goetz MP, Pérez EA, et al. A multidisciplinary approach to the management of breast cancer. Part 1: Prevention and diagnosis. Mayo Clin Proc. 2007;82:999-1012.
https://doi.org/10.4065/82.8.999
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Ramírez, G. Predictores genéticos En cáncer Mamario Importancia De La Prueba De 21 Genes Para Predecir La Tasa De Recurrencia Y La indicación De La Quimioterapia. Rev Colomb Cir 2010, 25, 300-308.
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