Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer.
BACKGROUND
High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many.


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.
Rodenhuis
S
S
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam. sroden@nki.nl
Bontenbal
M
M
van Hoesel
Q G C M
QG
Smit
W M
WM
Nooij
M A
MA
Voest
E E
EE
van der Wall
E
E
Hupperets
P
P
van Tinteren
H
H
Peterse
J L
JL
van de Vijver
M J
MJ
de Vries
E G E
EG
D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D011446:Prospective Studies; D016019:Survival Analysis
D018906:Antineoplastic Agents, Alkylating