PRIMARY OBJECTIVES:

I. To determine if 3-year recurrence-free survival (RFS) is greater than 92% among clinicalges II or IIIa patients with HER2-positive breast cancer who achieve pathologic complete(pCR) (ypT0/is ypN0) after preoperative therapy with 12 weeks of a taxane,uzumab (or Food and Drug Administration [FDA] approved biosimilar) and pertuzumab (THP x 12).

SECONDARY OBJECTIVES:

I. To determine 3-year IDFS (invasive disease-free survival), DDFS (distant disease-freeurvival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overallurvival) and breast cancer-specific survival in patients who achieve pCR (and byge). (Secondary Clinical Objective) II. To determine 3-year EFS (event-free survival) in all patients from time of study registration. (Secondary Clinicalbjective) III. To evaluate safety and tolerability for all patients during the pre-operativehase and for patients who attain pCR and de-escalate therapy (Arm A) until the completion ofurgery protocol assigned therapy (i.e. until the end of trastuzumab and pertuzumab [HP]herapy). (Secondary Clinical Objective) IV. To evaluate the association of estrogen receptor (ER) status in the untreated primary tumor with pathologic response and with long-termurvival outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specificurvival). (Secondary Correlative Objective) V. To evaluate the associations of detection ofulating tumor cells (CTCs) in the blood at baseline with pCR. (Secondary Correlativebjective) VI. To evaluate the association of detection of CTCs in the blood at baseline,3 weeks of THP, after 12 weeks of THP (before surgery), after surgery before anydditional therapy, and after completion of HER2-targeted therapy with RFS in patients whohieve pCR or not. (Secondary Correlative Objective)

EXPLORATORY OBJECTIVES:

I. To determine 3-year RFS, IDFS (invasive disease-free survival), DDFS (distant disease-freeurvival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overallurvival) and breast cancer-specific survival in patients who do not achieve pCR (and byge). (Exploratory Clinical Objective) II. To determine thehologic response to THP neoadjuvant therapy, as assessed by residual cancer burden (RCB). (Exploratory Clinical Objective) III. To determine the association between residual cancer burden (RCB) and all described standardized definitions for efficacy end points (STEEP)utcomes. (Exploratory Clinical Objective) IV. To determine the false negative rate (FNR) of limited staging procedures (defined as sentinel lymph node biopsy [SLNB] plusval of clipped node) in patients who undergo such procedures with a planned axillaryymph node dissection (ALND). (Exploratory Clinical Objective) V. To determine axillary pCRunction of the burden of disease at presentation as determined on pre-treatment ultrasound (US) and the axillary staging technique (SLNB plus ensuring removal of clippedde versus ALND). (Exploratory Clinical Objective) VI. To evaluate the associations betweenumor cell-free deoxyribonucleic acid (DNA) (cfDNA) tumor-specific mutations (baselined after therapy) with pathologic response and long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Exploratory Correlativebjective) VII. To evaluate the associations between tumor infiltrating lymphocytes (TILs)d immune activation gene signatures in the baseline tumor with pathologic response andg-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS and breast cancer-specificurvival). (Exploratory Correlative Objective) VIII. To determine the frequency of change inubtype between pretreatment tumor specimen and residual disease at the time ofurgery. (Exploratory Correlative Objective) IX. To evaluate the associations between DNAy number, DNA mutations, ribonucleic acid (RNA) expression and protein expression in the baseline tumor and changes from baseline to post-THP therapy with pathologic response andg-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specificurvival). (Exploratory Correlative Objective)

PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxelvenously (IV) on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of theg oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, anduzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard ofumpectomy and/or mastectomy.

POST-OPERATIVE/ADJUVANT THERAPY: Patients are assigned to 1 of 2 arms.

ARM A: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy andve hormone therapy if appropriate.

ARM B: Patients with remaining tumor after surgery receive standard of care trastuzumab14 doses in the absence of disease progression or unacceptable toxicity. Patients may also receive additional standard of care chemotherapy, as well as hormoneherapy if appropriate.

After completion of study treatment, patients are followed up every 3 months for 2 years,very 6 months for 2-5 years, then annually for 5-15 years from date of surgery.