Conditions: Breast Neoplasms
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 3222
Healthy volunteers: no

Brief summary:
Primary objective:

* Compare disease-free survival in women with human epidermal growth factor receptor 2 (HER2)-neu-expressing node-positive or high-risk node-negative operable breast cancer treated with adjuvant doxorubicin, cyclophosphamide, and docetaxel with or without trastuzumab (Herceptin) vs trastuzumab, docetaxel, and carboplatin.

Secondary objective:

* Compare overall survival of participants treated with these regimens.
* Compare the toxic effects (including cardiac) of these regimens in these participants.
* Compare quality of life of participants treated with these regimens.
* Compare pathologic and molecular markers for predicting efficacy of these regimens in these participants.
* For substudy: Compare peripheral levels of shed HER2-neu extracellular domain with fluorescence in situ hybridization in predicting outcome in participants treated with these regimens.

Detailed description:

Arms:
arm 1: Doxorubicin 60 mg/m² intravenous (IV) bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus injection on Day 1 of every 3 weeks for 4 cycles followed by docetaxel 100 mg/m² IV infusion every 3 weeks for another 4 cycles. arm 2: Doxorubicin 60 mg/m² IV bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus Injection on Day 1 of every 3 weeks for 4 cycles. Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 5, followed by Herceptin 2 mg/kg by IV infusion weekly starting from Day 8; and docetaxel 100 mg/m² IV infusion on Day 2 of Cycle 5, then on Day 1 of every 3 weeks for all subsequent cycles ( total 4 cycles). After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose. arm 3: Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 1 only, followed by Herceptin 2 mg/kg IV infusion weekly starting from Day 8 until three weeks after the last cycle of chemotherapy. Docetaxel 75 mg/ m² IV infusion on Day 2 of Cycle 1, then on Day 1 of all subsequent cycles followed by carboplatin IV infusion at target AUC = 6 mg/mL/min repeated every 3 weeks for a total of 6 cycles. After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg by IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose.

Interventions: intervention 1: Doxorubicin intervention 2: Cyclophosphamide intervention 3: Docetaxel intervention 4: Herceptin intervention 5: Carboplatin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol document: