Study treatment

Enrolled subjects received in the neoadjuvant setting chemotherapy consisting of intravenous 5-fluorouracil (500 mg/m²), epirubicin (75 mg/m²) and cyclophosphamide (500 mg/m²) (FEC) every 3 weeks (Q3W) for 3 cycles. Then, subjects were randomized to either arm A to receive intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) in combination with intravenous pertuzumab (840 mg intravenous loading dose, then 420 mg) and docetaxel (75 mg/m², escalating, if tolerated, to 100 mg/m²) Q3W for 4 cycles or arm B to receive SC trastuzumab (600 mg) and intravenous pertuzumab and docetaxel (at same doses of arm A) Q3W for 4 cycles. Surgery was given from 3 to 7 weeks after the last administration of the neoadjuvant treatment. Post surgery, each patient received trastuzumab Q3W for 14 cycles with the same formulation (SC or intravenous) and dosage used preoperatively. Radiotherapy and endocrine therapy for estrogen receptor (ER)-positive tumors were prescribed as per local standards. Dose modifications for trastuzumab (SC or intravenous) and pertuzumab were not permitted. Docetaxel dose reduction to 55 mg/m² (or 75 mg/m² if the dose was previously escalated to 100 mg/m²) was allowed; re-escalation was not permitted. FEC dose reductions were allowed as per local prescribing guidelines. Prophylactic use of granulocyte colony-stimulating factor was permitted.