Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer
Annals of Oncology , Volume 17 - Issue 4 p. 588- 596
Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil, epirubicin and cyclophosphamide) followed by radiation therapy and tamoxifen, or the same treatment but with high-dose alkylating chemotherapy (cyclophosphamide, thiotepa and carboplatin) replacing the fifth course of FEC. Of these patients, 621 had HER2/neu-negative disease, as determined by immunohistochemistry and chromogenic in situ hybridisation. Results: At a median follow-up of 84 months, a trend for a better relapse-free survival was observed in the high-dose arm: (hazard ratio (HR) 0.84, P = 0.076, two-sided). The 621 patients with HER2/neu-negative disease benefited from high-dose therapy, while patients with HER2/neu-positive disease did not (test for interaction, P = 0.006). There was a marked relapse-free survival benefit for patients with HER2/neu-negative disease (71.5% versus 59.1%, 5 years after randomisation; HR 0.68, P = 0.002) and also a survival benefit (78.2% versus 71.0% at 5 years; HR 0.72, P = 0.02). Conclusions: The findings from this subgroup analysis provide additional evidence that HER2/neu-positive breast cancer is relatively resistant to alkylating agents. For HER2/neu-negative tumours, however, high-dose chemotherapy should remain the subject of clinical studies.
|Adjuvant chemotherapy, Alkylating agents, Breast cancer, High-dose chemotherapy, Peripheral blood progenitor cell transplant|
|Annals of Oncology|
|Organisation||Department of Medical Oncology|
Rodenhuis, S, Bontenbal, M, van Hoesel, Q.G, Smit, W.M, Nooij, M.A, Voest, E.E, … de Vries, E.G.E. (2006). Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer. Annals of Oncology, 17(4), 588–596. doi:10.1093/annonc/mdl001