Breast Cancer Research and Treatment

, Volume 144, Issue 2, pp 307–318

Benefit from anthracyclines in relation to biological profiles in early breast cancer

Authors

    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
  • Sara Bravaccini
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
  • Emanuela Scarpi
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
  • Anita Mangia
    • National Cancer Research CentreIstituto Tumori ‘‘Giovanni Paolo II’’
  • Stella Petroni
    • National Cancer Research CentreIstituto Tumori ‘‘Giovanni Paolo II’’
  • Maurizio Puccetti
    • Santa Maria delle Croci Hospital
  • Laura Medri
    • Morgagni-Pierantoni Hospital
  • Luigi Serra
    • Morgagni-Pierantoni Hospital
  • Monica Ricci
    • Infermi Hospital
  • Serenella Cerasoli
    • Bufalini Hospital
  • Nicoletta Biglia
    • University of Turin, A.O. Mauriziano “Umberto I” Hospital
  • Roberta Maltoni
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
  • Donata Casadei Giunchi
    • Morgagni-Pierantoni Hospital
  • Lorenzo Gianni
    • Infermi Hospital
  • Amelia Tienghi
    • Santa Maria delle Croci Hospital
  • Mario Brandi
    • National Cancer Research CentreIstituto Tumori ‘‘Giovanni Paolo II’’
  • Monica Faedi
    • Bufalini Hospital
  • Piero Sismondi
    • University of Turin, A.O. Mauriziano “Umberto I” Hospital
  • Angelo Paradiso
    • National Cancer Research CentreIstituto Tumori ‘‘Giovanni Paolo II’’
  • Rosella Silvestrini
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
  • Dino Amadori
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
Clinical Trial

DOI: 10.1007/s10549-013-2819-0

Cite this article as:
Rocca, A., Bravaccini, S., Scarpi, E. et al. Breast Cancer Res Treat (2014) 144: 307. doi:10.1007/s10549-013-2819-0

Abstract

There are no validated predictors of benefit from anthracyclines. We compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF), and epirubicin in different sequences with CMF alone in a phase III trial on operable breast cancers. Outcomes were analyzed in relation to tumor biological profiles to identify potential predictors of the efficacy of different treatments/drug combinations. Patients with N− or 1–3N+ tumors, were randomized to receive (a) epirubicin (4 cycles) followed by CMF (4 cycles); (b) CMF (4 cycles) followed by epirubicin (4 cycles), or (c) CMF (6 cycles) alone. Immunohistochemical assessments of estrogen (ER) and progesterone (PgR) receptors, HER2 and Ki67 were available for 705 patients (arm A/B/C: 276/269/160). Prognostic and predictive relevance was analyzed by log-rank tests and Cox models. Ki67 > 20 % and absent/low expression of ER and PgR were associated with worsen disease-free (DFS) and overall survival (OS). In patients with triple negative tumors (ER−, PgR−, HER2−), epirubicin-containing regimens yielded better DFS (HR 0.33, 95 % CI 0.17–0.62, P = 0.0007) and OS (HR 0.24, 95 % CI 0.10–0.57, P = 0.001) compared with CMF alone, whereas no differences were found in patients with HER2-positive (HER2+, ER−, PgR−) subtype. Treatment by subtype interaction (HER2-positive vs. others) was significant for DFS (χ2 = 6.72, P = 0.009). In triple unfavorable (ER−, PgR−, Ki67 > 20 %) tumors, the use of epirubicin yielded better DFS (HR 0.45,95 % CI 0.26–0.78, P = 0.005) and OS (HR 0.30, 95 % CI 0.15–0.63, P = 0.001). Epirubicin-containing regimens seem to be superior to CMF alone in patients with highly proliferating, triple negative or triple unfavorable tumors .

Keywords

Breast cancerTumor subtypesAdjuvantPredictive factorsAnthracyclines

Abbreviations

CEF

Cyclophosphamide, epirubicin, fluorouracil

CIN

Chromosomal instability

Ch17CEP

Chromosome 17 centromere enumeration probe

CMF

Cyclophosphamide, methotrexate, and fluorouracil

DFS

Disease-free

ER

Estrogen receptor

HR

Hazard ratio

OS

Overall survival

PgR

Progesterone receptor

RPBC

Rapidly proliferating breast cancer

Copyright information

© Springer Science+Business Media New York 2013