Skip to main content
Top
Published in: Breast Cancer Research and Treatment 1/2010

01-08-2010 | Clinical trial

Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer

Authors: Miguel Martín, Álvaro Rodríguez-Lescure, Amparo Ruiz, Emilio Alba, Lourdes Calvo, Manuel Ruiz-Borrego, Ana Santaballa, César A. Rodríguez, Carmen Crespo, Mar Abad, Severina Domínguez, Jesús Florián, Cristina Llorca, Miguel Méndez, María Godes, Ricardo Cubedo, Adolfo Murias, Norberto Batista, María José García, Rosalía Caballero, Enrique de Álava

Published in: Breast Cancer Research and Treatment | Issue 1/2010

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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 21:976–983CrossRefPubMed 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 21:976–983CrossRefPubMed
2.
go back to reference 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 23:3686–3696CrossRefPubMed 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 23:3686–3696CrossRefPubMed
3.
go back to reference Martin M, Pienkowski T, Mackey J et al (2005) Adjuvant docetaxel for node positive breast cancer. N Engl J Med 352:2302–2313CrossRefPubMed Martin M, Pienkowski T, Mackey J et al (2005) Adjuvant docetaxel for node positive breast cancer. N Engl J Med 352:2302–2313CrossRefPubMed
4.
go back to reference 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 24:5664–5671CrossRefPubMed 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 24:5664–5671CrossRefPubMed
5.
go back to reference 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 24:5381–5387CrossRefPubMed 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 24:5381–5387CrossRefPubMed
6.
go back to reference 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 27:1177–1183CrossRefPubMed 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 27:1177–1183CrossRefPubMed
7.
go back to reference Martin M (2006) Molecular biology of breast cancer. Clin Trasl Oncol 8:7–14CrossRef Martin M (2006) Molecular biology of breast cancer. Clin Trasl Oncol 8:7–14CrossRef
8.
go back to reference Hayes DF, Thor AD, Dressler LG et al (2007) HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496–1506CrossRefPubMed Hayes DF, Thor AD, Dressler LG et al (2007) HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496–1506CrossRefPubMed
9.
go back to reference Parker JS, Mullins M, Cheang MC et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167CrossRefPubMed Parker JS, Mullins M, Cheang MC et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167CrossRefPubMed
10.
go back to reference 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 27:1168–1176CrossRefPubMed 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 27:1168–1176CrossRefPubMed
11.
go back to reference 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 100:805–814CrossRefPubMed 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 100:805–814CrossRefPubMed
12.
go back to reference 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 25:2127–2132CrossRefPubMed 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 25:2127–2132CrossRefPubMed
13.
go back to reference Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed
14.
go back to reference 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 27:1323–1333CrossRefPubMed 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 27:1323–1333CrossRefPubMed
15.
go back to reference 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 14:1368–1376CrossRefPubMed 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 14:1368–1376CrossRefPubMed
16.
go back to reference McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072CrossRefPubMed McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072CrossRefPubMed
17.
go back to reference Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef
18.
go back to reference Piccart-Gebhart M, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672CrossRefPubMed Piccart-Gebhart M, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672CrossRefPubMed
19.
go back to reference Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable her2-positive breast cancer. N Engl J Med 353:1673–1684CrossRefPubMed Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable her2-positive breast cancer. N Engl J Med 353:1673–1684CrossRefPubMed
20.
go back to reference 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 111:27–44CrossRefPubMed 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 111:27–44CrossRefPubMed
21.
go back to reference 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 100:14–20CrossRefPubMed 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 100:14–20CrossRefPubMed
22.
go back to reference 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 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
23.
go back to reference 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 27:2809–2815CrossRefPubMed 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 27:2809–2815CrossRefPubMed
24.
go back to reference 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 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
Metadata
Title
Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer
Authors
Miguel Martín
Álvaro Rodríguez-Lescure
Amparo Ruiz
Emilio Alba
Lourdes Calvo
Manuel Ruiz-Borrego
Ana Santaballa
César A. Rodríguez
Carmen Crespo
Mar Abad
Severina Domínguez
Jesús Florián
Cristina Llorca
Miguel Méndez
María Godes
Ricardo Cubedo
Adolfo Murias
Norberto Batista
María José García
Rosalía Caballero
Enrique de Álava
Publication date
01-08-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0663-z

Other articles of this Issue 1/2010

Breast Cancer Research and Treatment 1/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine