Statement: the primary trial and the secondary trial investigate the effects of their intervention on patient tpCR.
Primary_evidence: Outcome Measurement:    Progression Free Survival (PFS)   PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.   Time frame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016) Results 1:    Arm/Group Title: Ipatasertib and Paclitaxel   Arm/Group Description: Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.   Overall Number of Participants Analyzed: 62   Median (90% Confidence Interval)   Unit of Measure: Months  6.18        (4.57 to 7.33) Results 2:    Arm/Group Title: Placebo and Paclitaxel   Arm/Group Description: Participants randomised to receive paclitaxel 80 mg/m^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.   Overall Number of Participants Analyzed: 62   Median (90% Confidence Interval)   Unit of Measure: Months  4.93        (3.58 to 5.36)
Secondary_evidence: Outcome Measurement:    Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples   tpCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( that is [i.e.], ypT0/is, ypN0 in the American Joint Committee on Cancer [AJCC] staging system, 7th edition). Percentage of participants with tpCR was reported.   Time frame: Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months) Results 1:    Arm/Group Title: TCH + P   Arm/Group Description: Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).   Overall Number of Participants Analyzed: 221   Measure Type: Number   Unit of Measure: Percentage of Participants  56.1        (49.29 to 62.76) Results 2:    Arm/Group Title: T-DM1 + P   Arm/Group Description: Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).   Overall Number of Participants Analyzed: 223   Measure Type: Number   Unit of Measure: Percentage of Participants  44.4        (37.76 to 51.18)