Safety and Efficacy Comparison of Docetaxel and Ixabepilone in Non Metastatic Poor Prognosis Breast Cancer

DISEASE CHARACTERISTICS:

Inclusion criteria:

Histologically proven invasive unilateral breast cancer (regardless of the type)

Initial clinical condition compatible with complete initial resection
No residual macro or microscopic tumor after surgical excision

Node-positive disease (i.e., positive sentinel node or positive axillary clearance) (N+) or node-negative disease (-) meeting the following criteria :

Stage II or III disease
pT >20 mm (T1-4)

Patients must meet 1 of the following hormone-receptor criteria:

Node-positive patients: triple-negative* tumor (HER2 negative, estrogen-receptor [ER] negative, and progesterone receptor [PR] negative) OR double-negative (HER2 negative, PR negative, and ER+)
Node-negative patients: triple-negative* tumor only
NOTE: *Hormone-receptor negativity is defined as ER <10% and PR <10% by IHC and HER2 negativity is defined as IHC 0-1+ OR IHC 2+ and FISH or CISH negative
Must be able to begin chemotherapy no later than day 49 after the initial surgery

Exclusion criteria:

Clinically or radiologically detectable metastases (M0)
Bilateral breast cancer or contralateral ductal carcinoma in situ
Any metastatic impairment, including homolateral subclavicular node involvement, regardless of its type
Any tumor ≥T4a (cutaneous invasion, deep adherence, inflammatory breast cancer)
HER 2 overexpression defined as IHC 3+ OR IHC 2+ and FISH or CISH positive
Any clinically or radiologically suspect and non-explored damage to the contralateral breast

PATIENT CHARACTERISTICS:

Inclusion criteria:

Female
Pre- or postmenopausal
ECOG performance status 0-1
Peripheral neuropathy ≤grade 1
Neutrophil count ≥2,000/mm³
Platelet count ≥100,000/mm³
Hemoglobin >9 g/dL
AST and ALT ≤1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤2.5 times ULN
Total bilirubin ≤1.0 times ULN
Serum creatinine ≤1.5 times ULN
LVEF ≥50% by MUGA scan or echocardiography
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for up to 8 weeks after completion of study treatment

Exclusion criteria:

Previous cancer (except cutaneous baso-cellular epithelioma or uterine peripheral epithelioma) in the preceding 5 years, including invasive contralateral breast cancer
Patients with any other concurrent severe and/or uncontrolled medical disease or infection that could compromise participation in the study

Clinically significant cardiovascular disease within the past 6 months including any of the following:

Unstable angina
Congestive heart failure
Uncontrolled hypertension (i.e., blood pressure >150/90 mm Hg)
Myocardial infarction
Cerebral vascular accidents
Known prior severe hypersensitivity reactions to agents containing Cremophor EL
Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Patients deprived of liberty or placed under the authority of a tutor

PRIOR CONCURRENT THERAPY:

At least 2 weeks since prior minor surgery (excluding breast biopsy) and adequately recovered
At least 3 weeks since prior major surgery and adequately recovered
No prior chemotherapy, hormonal therapy, or radiotherapy

More than 72 hours since prior and no concurrent treatment with any of the following strong inhibitors of CYP3A4:

Amiodarone
Clarithromycin
Amprenavir
Delavirdine
Voriconazole
Erythromycin
Fluconazole
Itraconazole
Ketoconazole
Indinavir
Nelfinavir
Ritonavir
Saquinavir
No concurrent participation in another therapeutic trial involving an experimental drug