Breast Cancer Research and Treatment

, Volume 132, Issue 3, pp 843–851

Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design (ECTO II)

  • Milvia Zambetti
  • Mauro Mansutti
  • Patricia Gomez
  • Ana Lluch
  • Christian Dittrich
  • Claudio Zamagni
  • Eva Ciruelos
  • Lorenzo Pavesi
  • Vladimir Semiglazov
  • Elena De Benedictis
  • Fernando Gaion
  • Mario Bari
  • Paolo Morandi
  • Pinuccia Valagussa
  • Gianni Luca
Clinical Trial

DOI: 10.1007/s10549-011-1660-6

Cite this article as:
Zambetti, M., Mansutti, M., Gomez, P. et al. Breast Cancer Res Treat (2012) 132: 843. doi:10.1007/s10549-011-1660-6

Abstract

Sequential doxorubicin/paclitaxel (AT) followed by CMF treatment was shown to be an active neoadjuvant chemotherapy regimen in the first European Cooperative Trial in Operable Breast Cancer (ECTO I trial). The aim of the current study (ECTO II) is to assess the complete pathological response (pCR) rate following three different anthracycline and taxane-containing neoadjuvant chemotherapy regimens, with or without capecitabine (X). Patients with operable, invasive breast cancer >2.0 cm in diameter, were randomized to AT→CMF, AT→CMX or AC→TX regimens in two parallel, randomized, open-label, phase II trials (within a single study) in patients with estrogen receptor negative (ER−) and estrogen receptor positive (ER+) diseases, respectively. Exemestane was delivered concomitantly with neoadjuvant chemotherapy in ER+ tumors. Achievement of pCR was more common in ER− than ER+ women (45.3 vs. 10.4%). Capecitabine was only associated with a higher frequency of pCR in ER+ patients receiving AT→CMX. Overall response rates (ORR) ranged from 88 to 97%, and this translated into high rates of breast-conserving surgery (67% of ER− patients and 72% of ER+ patients). All three regimens were well tolerated. Febrile neutropenia and gastrointestinal effects were the most common grade ≥3 adverse events. As expected, the ECTO II study showed higher pCR rates in patients with ER− disease. Substituting capecitabine for fluorouracil (± methotrexate) in anthracycline/taxane-containing regimens appeared to be beneficial only in ER+ tumors. Translational studies investigating interactions between therapeutic agents and tumor biology are warranted to refine patient selection and improve the results of neoadjuvant chemotherapy.

Keywords

ChemotherapyTaxaneCapecitabinePathological complete remissionpCR

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Milvia Zambetti
    • 1
    • 14
  • Mauro Mansutti
    • 2
  • Patricia Gomez
    • 3
  • Ana Lluch
    • 4
  • Christian Dittrich
    • 5
  • Claudio Zamagni
    • 6
  • Eva Ciruelos
    • 7
  • Lorenzo Pavesi
    • 8
  • Vladimir Semiglazov
    • 9
  • Elena De Benedictis
    • 1
  • Fernando Gaion
    • 10
  • Mario Bari
    • 11
  • Paolo Morandi
    • 12
  • Pinuccia Valagussa
    • 13
  • Gianni Luca
    • 1
    • 14
  1. 1.Fondazione IRCCS Istituto Nazionale TumoriMilanItaly
  2. 2.Ospedale Universitario Santa Maria della MisericordiaUdineItaly
  3. 3.Hospital General Vall d’HebronBarcelonaSpain
  4. 4.Hospital Clínico Universitario de ValenciaValenciaSpain
  5. 5.LBI-ACR & ACR-ITR VIEnna, Kaiser Franz Josef-SpitalViennaAustria
  6. 6.Ospedale Policlinico S.Orsola MalpighiBolognaItaly
  7. 7.Hospital Universitario 12 de OctubreMadridSpain
  8. 8.Fondazione Salvatore MaugeriPaviaItaly
  9. 9.NN Petrov Research Institute of OncologySt. PetersburgRussian Federation
  10. 10.Ospedale Civile di CamposampieroCamposampieroItaly
  11. 11.Presidio Ospedaliero di NoaleNoaleItaly
  12. 12.Ospedale S. BortoloVicenzaItaly
  13. 13.Fondazione MichelangeloMilanItaly
  14. 14.Fondazione Centro San Raffaele del Monte TaborMilanoItaly