Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer.
OBJECTIVE
To compare preoperative intense dose-dense (IDD) chemotherapy with conventionally scheduled preoperative chemotherapy in high-risk primary breast cancer (BC).


METHODS
In this randomized phase III trial a total of 668 eligible primary BC patients stratified for tumors > or = 3 cm (n = 567) or inflammatory BC (n = 101) were randomly assigned to receive concurrent preoperative epirubicin/paclitaxel every 3 weeks or dose-dense and dose-escalated sequential epirubicin followed by paclitaxel every 2 weeks. All patients received three cycles of cyclophosphamide, methotrexate, and fluorouracil chemotherapy after surgery.


RESULTS
IDD treatment significantly improved pathologic complete response rate (18% v 10%; odds ratio [OR] 1.89; P = .008), disease-free survival (DFS; hazard ratio [HR], 0.71; P = .011), and overall survival (OS; HR, 0.83; P = .041) compared to epirubicin/paclitaxel. Patients with inflammatory BC had a particularly poor prognosis and did not appear to benefit from IDD therapy in this trial (DFS HR, 1.10; P = .739; OS HR, 1.25; P = .544). In contrast, patients with noninflammatory BC significantly benefited from IDD treatment (DFS HR, 0.65, P = .005; OS HR, 0.77, P = .013). Treatment effects in multivariate analysis were significant for noninflammatory BC (DFS HR, 0.65, P = .015; OS HR, 0.79, P = .034), but not for all patients (DFS HR, 0.76; P = .088; OS HR, 0.82; P = .059). IDD therapy was associated with significantly more nonhematologic toxicities, anemia, and thrombocytopenia, but with similar neutropenia and infection rates.


CONCLUSIONS
Our results support the efficacy and short-term safety of IDD as preoperative chemotherapy. IDD was less well tolerated compared to standard treatment, but improved clinical outcomes in patients with noninflammatory high-risk primary BC.
Untch
Michael
M
Helios Klinikum, Campus Berlin Buch, Berlin, Germany.
Möbus
Volker
V
Kuhn
Walther
W
Muck
Bernd Rudolph
BR
Thomssen
Christoph
C
Bauerfeind
Ingo
I
Harbeck
Nadia
N
Werner
Christoph
C
Lebeau
Annette
A
Schneeweiss
Andreas
A
Kahlert
Stephen
S
von Koch
Franz
F
Petry
Karl Ulrich
KU
Wallwiener
Diethelm
D
Kreienberg
Rolf
R
Albert
Ute-Susann
US
Lück
Hans-Joachim
HJ
Hinke
Axel
A
Jänicke
Fritz
F
Konecny
Gottfried E
GE
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D011379:Prognosis; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D015251:Epirubicin; D017239:Paclitaxel