Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer (original) (raw)

Abstract

Treatment with fluororacil, epirubicin, and cyclophosphamide followed by weekly paclitaxel (FEC-P) yielded superior disease-free survival than FEC in the adjuvant breast cancer trial GEICAM 9906. We evaluate molecular subtypes predictive of prognosis and paclitaxel response in this trial. Two molecular subtype classifications based on conventional immunohistochemical and fluorescent in situ hybridization determinations were used: #1: Four groups segregated according to the combination of hormone receptor (HR) and HER2 status; #2: Intrinsic subtype classification (Triple Negative (TN), HER2, Luminal B and Luminal A). Results: Both subtype classifications yielded prognostic and predictive information. HR +/HER2− patients (and Luminal A patients) had a significantly better outcome than the other subgroups of patients. The superiority of FEC-P over FEC was clearly more marked in HR−/HER2− patients (TN patients), particularly in the subset with basal phenotype (TN and either EGFR+ or cytokeratins 5/6+). The Luminal A subtype also achieved a significant benefit with FEC-P. The molecular-defined subgroup of TN was clearly predictive of better response to treatment with FEC-P. Luminal A patients had the best prognosis and also have a better outcome with weekly paclitaxel.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Henderson IC, Berry DA, Demetri GD et al (2003) Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21:976–983
    Article CAS PubMed Google Scholar
  2. Mamounas EP, Bryant J, Lembersky BC et al (2005) Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for nodepositive breast cancer: results from NSABP-B 28. J Clin Oncol 23:3686–3696
    Article CAS PubMed Google Scholar
  3. Martin M, Pienkowski T, Mackey J et al (2005) Adjuvant docetaxel for node positive breast cancer. N Engl J Med 352:2302–2313
    Article CAS PubMed Google Scholar
  4. Roche H, Fumoleau P, Spielmann M et al (2006) Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PASC 01 Trial. J Clin Oncol 24:5664–5671
    Article CAS PubMed Google Scholar
  5. Jones SE, Savin MA, Holmes FA et al (2006) Phase iii trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24:5381–5387
    Article CAS PubMed Google Scholar
  6. Jones S, Holmes FA, O′Shaughnessy JO et al (2009) Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US oncology research trial 9735. J Clin Oncol 27:1177–1183
    Article CAS PubMed Google Scholar
  7. Martin M (2006) Molecular biology of breast cancer. Clin Trasl Oncol 8:7–14
    Article CAS Google Scholar
  8. Hayes DF, Thor AD, Dressler LG et al (2007) HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496–1506
    Article CAS PubMed Google Scholar
  9. Parker JS, Mullins M, Cheang MC et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167
    Article PubMed Google Scholar
  10. Hugh J, Hanson J, Cheang MCU et al (2009) Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 27:1168–1176
    Article CAS PubMed Google Scholar
  11. Martin M, Rodriguez-Lescure A, Ruiz A et al (2008) Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst 100:805–814
    Article CAS PubMed Google Scholar
  12. Hudis CA, Barlow WE, Costantino JP et al (2007) Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 25:2127–2132
    Article PubMed Google Scholar
  13. Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168
    CAS PubMed Google Scholar
  14. Sauter G, Lee J, Barlett JMS, Slamon DJ, Press MF (2009) Guidelines for human epidermal growth factor receptor 2 testing: biological and methodological considerations. J Clin Oncol 27:1323–1333
    Article CAS PubMed Google Scholar
  15. Cheang MCU, Voduc D, Badjik C et al (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14:1368–1376
    Article CAS PubMed Google Scholar
  16. McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072
    Article PubMed Google Scholar
  17. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
    Article Google Scholar
  18. Piccart-Gebhart M, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672
    Article CAS PubMed Google Scholar
  19. Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable her2-positive breast cancer. N Engl J Med 353:1673–1684
    Article CAS PubMed Google Scholar
  20. Tan DSP, Marchio C, Jones RL et al (2007) Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracyline-treated patients. Breast Cancer Res Treat 111:27–44
    Article PubMed CAS Google Scholar
  21. Gennari A, Sormani MP, Pronzato P et al (2008) HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 100:14–20
    Article CAS PubMed Google Scholar
  22. Cheang M, Chia SK, Tu D et al (2009) Anthracyclines in basal breast cancer: the NCI-CTG trial MA5 comparing adjuvant CMF to CEF. J Clin Oncol 27(15s):519
    Google Scholar
  23. Penault-Llorca F, André F, Sagan C et al (2009) Ki 67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 27:2809–2815
    Article CAS PubMed Google Scholar
  24. Jacquemier J, Penault-Llorca F, Mnif H et al (2006) Identification of a basal-like subtype and comparative effect of epirubicin-based chemotherapy and sequential epirubicin followed by docetaxel chemotherapy in the PACS 01 breast cancer trial: 33 markers studied on tissue-microarrays (TMA). J Clin Oncol 24(18S):509
    Google Scholar

Download references

Acknowledgments

The authors thank Maribel Casas, and María José Escudero (GEICAM) for their assistance in preparing the manuscript. Editorial help was by Peter R. Turner of t-SciMed (Reus, Spain). This work was supported, in part, by grants from Bristol-Myers Squibb and Pharmacia.

Author information

Authors and Affiliations

  1. Servicio de Oncología Médica, Departmento de Oncología, Hospital General Universitario Gregorio Marañón, c/Maiquez 7, 28009, Madrid, Spain
    Miguel Martín
  2. Department of Medical Oncology, Hospital Universitario de Elche, Elche, Spain
    Álvaro Rodríguez-Lescure
  3. Department of Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain
    Amparo Ruiz
  4. Department of Medical Oncology, Hospital Virgen de la Victoria, Málaga, Spain
    Emilio Alba
  5. Department of Medical Oncology, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain
    Lourdes Calvo
  6. Department of Medical Oncology, Hospital Vírgen del Rocío, Sevilla, Spain
    Manuel Ruiz-Borrego
  7. Department of Medical Oncology, Hospital La Fe, Valencia, Spain
    Ana Santaballa
  8. Department of Medical Oncology, Hospital Universitario de Salamanca, Salamanca, Spain
    César A. Rodríguez
  9. Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain
    Carmen Crespo
  10. Department of Cellular Biology and Pathology, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain
    Mar Abad
  11. Department of Medical Oncology, Hospital Txagorritxu, Vitoria, Spain
    Severina Domínguez
  12. Department of Medical Oncology, Hospital Comarcal Barbastro, Barbastro, Spain
    Jesús Florián
  13. Department of Medical Oncology, Hospital de Elda, Elda, Spain
    Cristina Llorca
  14. Department of Medical Oncology, Hospital General de Móstoles, Móstoles, Spain
    Miguel Méndez
  15. Department of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain
    María Godes
  16. Department of Medical Oncology, Hospital Puerta de Hierro, Madrid, Spain
    Ricardo Cubedo
  17. Department of Medical Oncology, Hospital Universitario Insular, Las Palmas, Spain
    Adolfo Murias
  18. Department of Medical Oncology, Hospital Universitario De Canarias, Tenerife, Spain
    Norberto Batista
  19. Department of Medical Oncology, Hospital General de Ciudad Real, Ciudad Real, Spain
    María José García
  20. GEICAM, Madrid, Spain
    Rosalía Caballero
  21. Molecular Pathology, Centro de Investigación del Cancer-IBMCC, Universidad de Salamanca- CSIC, Salamanca, Spain
    Enrique de Álava

Authors

  1. Miguel Martín
  2. Álvaro Rodríguez-Lescure
  3. Amparo Ruiz
  4. Emilio Alba
  5. Lourdes Calvo
  6. Manuel Ruiz-Borrego
  7. Ana Santaballa
  8. César A. Rodríguez
  9. Carmen Crespo
  10. Mar Abad
  11. Severina Domínguez
  12. Jesús Florián
  13. Cristina Llorca
  14. Miguel Méndez
  15. María Godes
  16. Ricardo Cubedo
  17. Adolfo Murias
  18. Norberto Batista
  19. María José García
  20. Rosalía Caballero
  21. Enrique de Álava

Corresponding author

Correspondence toMiguel Martín.

Additional information

This study is conducted on behalf of the GEICAM 9906 study investigators.

Appendix

Appendix

The following investigators, with their affiliations, participated in the GEICAM 9906 trial:

Hospital General Universitario Gregorio Marañón, Madrid, Spain—M. Martín and J. A. LópezGarcía-Asenjo; Hospital Universitario de Elche, Elche, Spain—Á. Rodríguez-Lescure; Instituto Valenciano de Oncología, Valencia, Spain—A. Ruiz and S.Almenar; Hospital Virgen de la Victoria, Málaga, Spain—E. Alba and L. Vicioso;Complexo Hospitalario Universitario A Coruña, La Coruña, Spain—L. Calvo and M. D. Guitián; Hospital Vírgen del Rocío, Sevilla, Spain—M. Ruiz-Borrego and J. Palacios; Hospital La Fe, Valencia, Spain—B. Munárriz and F. Vera; Hospital Universitario de Salamanca, Salamanca, Spain—C. A. Rodríguez; Hospital Ramón y Cajal, Madrid, Spain—C. Crespo and J. F. González-Palacios; Centro Oncológico de Galicia, La Coruña, Spain—M. Ramos and A. de la Cruz; Hospital de Cabueñes, Gijón, Spain—J. M. Gracia and J. Martín; Hospital Clínico de Valencia, Valencia, Spain—A. Lluch and J. Ferrer; Hospital Donostia, San Sebastián, Spain—I. Álvarez and I. Ruiz; Hospital Parc Taulí, Sabadell, Spain—M. Á. Seguí and A. Sáez; Hospital Clínico Lozano Blesa, Zaragoza, Spain—J. I. Mayordomo and M. Moros; Hospital Miguel Servet, Zaragoza, Spain—A. Antón and M. José Ríos; Complejo Hospitalario Puerta del Mar, Cádiz, Spain—J. M. Baena and M. J. Palomo; Instituto Oncológico de Guipúzcoa, San Sebastián, Spain—A. Plazaola and R. Rezola; Clínica Corachan, Barcelona, Spain—A. Modolell and P. de las Heras; Hospital Universitario San Joan de Reus, Reus, Spain—A. Pelegrí and F. Riu; Complejo Hospitalario Xeral Calde, Lugo, Spain—J. R. Mel and J. Alba; Hospital Provincial de Córdoba, Córdoba, Spain—E. Aranda and E. Fuentes; Hospital General de Alicante, Alicante, Spain—E. Adrover and G. Peiró; Hospital Provincial de Zamora, Zamora, Spain—J. V. Álvarez and J. C. Solera; Hospital San Cecilio de Granada, Granada, Spain—J. L. G. Puche and J. Aneiros; Hospital Ciudad de Jaén, Jaén, Spain—P. Sánchez-Rovira and C. Cueva; Hospital Mutua de Terrasa, Terrasa, Spain—S. Gonzalez and A. Salas; Hospital Marqués de Valdecilla, Santander, Spain—J. M. López-Vega and M. Francisca Garijo; Hospital Txagorritxu, Vitoria, Spain—S. Domínguez and Mª. A. Viguri; Hospital Comarcal Barbastro, Barbastro, Spain—J. Florian and R. Oncins; Hospital Universitario De Canarias, Tenerife, Spain—N. Batista and R. Méndez; Hospital de Elda, Elda, Spain—C. Llorca and S. Alonso Hernández; Hospital General de Móstoles, Móstoles, Spain—M. Méndez and M. J. Mestre; Hospital Clínico Barcelona, Barcelona, Spain—M. Muñoz and P. Fernández; Hospital General Universitario de Valencia, Valencia, Spain—Mª. J. Godes and A. Pérez; Hospital General de Ciudad Real, Ciudad Real, Spain—M. J. García and M. Carbajo; Hospital Puerta de Hierro, Madrid, Spain—R. Cubedo and E. Tejerina; Althaia Xarxa Assistencial Manresa, Manresa, Spain—I. Guash and L. Sardans; Hospital General de Jerez, Jerez, Spain—A. Moreno and A. Rodríguez; Hospital Universitario Insular, Las Palmas, Spain—A. Murias and M. Pavcovich; Fundación Hospital de Alcorcón, Alcorcón, Spain—C. Jara and M.Argüelles; Hospital Juan Ramón Jiménez, Huelva, Spain—B. Calero and J.Conde; Hospital Arnau de Vilanova, Lérida, Spain—V. Alberola and J. Fernando;Hospital General Universitario de Guadalajara, Guadalajara, Spain—J. Casinello and J. Cuevas; Hospital Municipal de Badalona, Badalona, Spain—I. Moreno and M. Gómez; Hospital de Cruces, Barakaldo, Spain—J. R. Barceló and J. Mª Ribera; Hospital del Mar, Barcelona, Spain—I. Tusquets and J. Mª Corominas; Hospital de León, León, Spain—A. García and T. Arribas; Complejo Hospitalario de Orense, Orense, Spain—J. García and C. Peñin; Hospital Río Carrión, Palencia, Spain—A. Arizcum and L. Pérez; Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas, Spain—J. Aguiar and M. A. Limeres; Hospital Virgen de la Salud, Toledo, Spain—M. A. de la Cruz and J. Martín; Hospital de L′Esperit Sant, Santa Coloma de Gramenet, Spain—C. Martín and Mª A. Ruiz; Hospital de la Ribera, Valencia, J. Miguel and R. Cano; Hospital de Navarra, Pamplona, Spain; J. J. Valerdi and A. Córdoba; Hospital Universitario de Valladolid, Valladolid, Spain—F. López and I. Peral; Hospital Morales Messeguer, Murcia, Spain—F. Ayala and M. A. Chaves; Hospital Germans Trias y Pujol, Badalona, Spain—A. Barnadas and E. Castellá; Hospital Virgen de los Lírios, Alicante, Spain—A. Oltra and J. L. Losa; Hospital Universitario Puerto Real, Puerto Real, Spain—A. Lorenzo and A. Hens; Hospital Doctor Peset, Valencia, Spain—D. Almenar and J. Escandón; Hospital Consorci Sanitari Terrasa, Terrassa, Spain—A. Arcusa and I. Roig; Hospital Puerto de Sagunto, Valencia, Spain—A. Galán and B. Martínez; Hospital de la Arrixaca, Murcia, Spain—J. L. Alonso and J. Bermejo; Hospital Provincial de Toledo, Toledo, Spain—P. Puñal and C. Pérez.

Rights and permissions

About this article

Cite this article

Martín, M., Rodríguez-Lescure, Á., Ruiz, A. et al. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer.Breast Cancer Res Treat 123, 149–157 (2010). https://doi.org/10.1007/s10549-009-0663-z

Download citation

Keywords