This is a randomized phase II study to evaluate the pathological complete response (pCR) rate with two neoadjuvant regimens (Docetaxel+Carboplatin+Herceptin/Perjeta and Docetaxel+Herceptin/Perjeta) in HER2 amplified/positive early breast cancer.

Inclusion Criteria:

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• 18 years of age or older
• Histologically confirmed cT2-T3 N0-N2, cT1 N1-N2, or cTX N1-N2 HER2 positive breast cancer (The invasive tumor must be HER2-positive based on the current ASCO-CAP guidelines; Patients are eligible regardless of estrogen receptor (ER) or progesterone receptor (PR) expression status. However, percentage of both ER and PR positivity must be documented in the pathology report.)
• No previous ipsilateral breast surgery for the current breast cancer
• No previous chemotherapy, anti-HER2 therapy, immunotherapy, endocrine therapy, or radiotherapy for the current breast cancer
• ECOG Performance Status 0-1 documented within 28 days prior to the start of study treatment (Appendix A)
• Breast and axillary imaging (including mammogram, ultrasound and/or MRI, per standard of care) within 49 days (7 weeks) prior to treatment initiation
• Subjects with clinically and/or radiographically abnormal axillary or internal mammary lymph nodes should have pathologic confirmation of disease status with image-guided biopsy or fine needle aspiration unless deemed medically unsafe
• Co-enrollment in the PRO-HER2 (HSC #160944) observational registry protocol
• Archival breast tumor tissue has been obtained or has been requested for use, which should include either a formalin-fixed paraffin-embedded (FFPE) block, or sixteen slides (fourteen 5-micron uncharged unstained slides plus either two H&E slides or two 5-micron charged unstained slides) - from primary breast tumor only.
• Subjects with bilateral synchronous HER2 positive breast cancer are eligible if they meet other eligibility criteria
• Neuropathy: No baseline grade 2 or above neuropathy
• Not pregnant, not breastfeeding, and at least one of the following applies: Not a woman of reproductive potential as defined by institutional standards; A woman of reproductive potential who agrees to follow contraceptive guidelines per institutional standards
• Adequate organ function, defined as follows: Hematologic (assessed ≤ 21 days of treatment initiation): Absolute neutrophil count ≥ 1,500/μL (with the exception of patients with documented Fy(a-/b-) (Duffy null) immunophenotype, in which case absolute neutrophil count ≥1,200/uL is allowed), Platelets ≥ 100,000/μL, Leukocytes ≥ 3,000/μL, Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (must be met without erythropoietin dependency and without erythrocyte transfusion within the last two weeks); Hepatic (assessed ≤ 21 days of treatment initiation): Total bilirubin ≤ 1.5x ULN, AST(SGOT) and ALT(SPGT) ≤ 2x ULN, Serum albumin ≥ 3.0 g/dL; Cardiac (assessed ≤ 49 days of treatment initiation): Normal baseline echocardiogram or MUGA scan including LVEF ≥ 50%, per standard of care

Exclusion Criteria:

• Current or anticipated use of other investigational agents while participating in this study
• Clinically or radiographically detected metastatic disease
• Inflammatory breast cancer
• Prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen. Note: Patients with squamous cell or basal cell carcinoma of the skin, ductal carcinoma in situ (DCIS) of the breast, or carcinoma in situ (CIS) of the uterine cervix who have undergone definitive therapy are not excluded from participation
• History of allergic reactions attributed to carboplatin, docetaxel, trastuzumab, or pertuzumab
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of this study, interfere with the subject's participation for the full duration of the study, or it is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Pregnancy, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. There is a potential for congenital abnormalities and for this regimen to harm breastfeeding infants.