• Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) [ Time Frame: Pre-dose at Cycle 8 (one cycle is 21 days) ]
• Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) [ Time Frame: Pre-dose at Cycle 8 (one cycle is 21 days) ]

• Percentage of Participants with Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment [ Time Frame: Following completion of surgery (up to 33 weeks) ]
  tpCR is defined as eradication of invasive disease in the breast and axilla (i.e., ypT0/isypN0)
• Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria [ Time Frame: From date of surgery to iDFS (excluding SPNBC) event (up to 5 years) ]
  iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.
• Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria [ Time Frame: From date of surgery to iDFS (including SPNBC) event (up to 5 years) ]
  iDFS including SPNBC is defined in the same way as iDFS but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
• Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria [ Time Frame: From baseline to EFS (excluding SPNBC) event (up to 5.5 years) ]
  EFS (excluding SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.
• Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria [ Time Frame: From baseline to EFS (including SPNBC) event (up to 5.5 years) ]
  EFS including SPNBC is defined in the same way as EFS, but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
• Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria [ Time Frame: From baseline to DFRI event (up to 5.5 years) ]
  DRFI is defined as the time between randomization and the date of distant breast cancer recurrence.
• Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival [ Time Frame: From baseline to death from any cause (up to 5.5 years) ]
• Number of Participants with At Least One Adverse Event by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4) [ Time Frame: From baseline until study completion (up to 5.5 years) ]
• Number of Participants with a Symptomatic Ejection Fraction Decrease (Heart Failure) of NYHA Class III or IV and a Drop in Left Ventricular Ejection Fraction (LVEF) of at Least 10-Percentage Points from Baseline and to Below 50% [ Time Frame: From baseline until study completion (up to 5.5 years) ]
  New York Heart Association (NYHA) Class III is defined as: Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. NYHA Class IV is defined as: Inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.
• Number of Participants Who Died from a Definite or Probable Cardiac Death [ Time Frame: From baseline until study completion (up to 5.5 years) ]
  Definite cardiac death is defined as death due to heart failure, myocardial infarction, or documented primary arrhythmia. Probable cardiac death is defined as sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology.
• Number of Participants with an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II [ Time Frame: From baseline until study completion (up to 5.5 years) ]
  An LVSD ("Ejection fraction decreased") of NYHA Class II is defined as an LVEF decrease of ≥10-percentage points below the baseline measurement to an absolute LVEF value of <50%, confirmed by a second assessment within approximately 3 weeks confirming a decrease of ≥10-percentage points below the baseline measurement and to an absolute LVEF value of <50%.

• Drug: Pertuzumab IV
  Pertuzumab will be administered as a fixed non-weight-based loading dose of 840-milligrams (mg) IV and then a 420-mg IV maintenance dose Q3W.
  Other Names:

  • Perjeta
  • RO4368451
• Drug: Trastuzumab IV
  Trastuzumab will be administered as an 8-milligram per kilogram of body weight (mg/kg) IV loading dose and then 6 mg/kg IV maintenance dose Q3W.
  Other Names:

  • Herceptin
  • RO0452317
• Drug: Pertuzumab and Trastuzumab FDC SC
  The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be administered SC at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab Q3W.
  Other Names:

  • Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf
  • PHESGO™
  • PH FDC SC
  • RG6264
  • RO7198574
• Drug: Doxorubicin
  Doxorubicin 60 milligrams per meter squared of body surface area (mg/m^2) will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.
• Drug: Cyclophosphamide
  Cyclophosphamide 600 mg/m^2 will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.
• Drug: Docetaxel
  Docetaxel 75 mg/m^2 will be administered IV on Day 1 of Cycle 5. At the investigator's discretion the dose may be escalated to 100 mg/m^2 IV for Cycles 6-8 (Q3W) provided no dose-limiting toxicity occurs.
• Procedure: Surgery
  Participants in both cohorts are scheduled to undergo surgery after 8 cycles of neoadjuvant therapy. Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice.
• Radiation: Post-Operative Radiotherapy
  If indicated, radiotherapy is given after chemotherapy and surgery, during adjuvant HER2-targeted therapy and hormone therapy (for hormone-receptor positive disease).
• Drug: Hormone Therapy
  For hormone receptor positive breast cancer, tamoxifen or aromatase inhibitors will be allowed as adjuvant hormone therapy for postmenopausal participants and with ovarian suppression or ablation for premenopausal participants in countries where it has been registered for this indication. Its use must be consistent with the registered label. Hormone therapy is given after chemotherapy and surgery during adjuvant HER2-targeted therapy.

• Active Comparator: Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
  Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab will be given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
  Interventions:

  • Drug: Pertuzumab IV
  • Drug: Trastuzumab IV
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide
  • Drug: Docetaxel
  • Procedure: Surgery
  • Radiation: Post-Operative Radiotherapy
  • Drug: Hormone Therapy
• Experimental: Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
  Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) of will be given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of the PH FDC SC for a total of 18 cycles.
  Interventions:

  • Drug: Pertuzumab and Trastuzumab FDC SC
  • Drug: Doxorubicin
  • Drug: Cyclophosphamide
  • Drug: Docetaxel
  • Procedure: Surgery
  • Radiation: Post-Operative Radiotherapy
  • Drug: Hormone Therapy

Inclusion Criteria:

• Ability to comply with the study protocol, in the investigator's judgment
• Eastern Cooperative Oncology Group (ECOG) Performance Status greater or equal to (≤)1
• Stage II-IIIC (T2-T4 plus any N, or any T plus N1-3, M0), locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer
• Primary tumor greater than (>)2 centimeters (cm) in diameter, or node-positive disease (clinically or on imaging, and node positivity confirmed with cytology and/or histopathology)
• Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies
• Hormone receptor status of the primary tumor, centrally confirmed
• Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy
• Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue for central confirmation of HER2, hormone receptor status, and PIK3CA mutational analyses
• Baseline left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective non-hormonal contraceptive method with a failure rate of less than (<)1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as specified in the protocol
• A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women <12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)
• No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment

Exclusion Criteria:

• Stage IV (metastatic) breast cancer
• History of invasive breast cancer
• History of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin
• Have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, endocrine therapy [selective estrogen receptor modulators, aromatase inhibitors], and antitumor vaccines) for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer
• Have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast
• High-risk for breast cancer and have received chemopreventative drugs in the past
• Multicentric (multiple tumors involving more than one quadrant) breast cancer, unless all tumors are HER2-positive
• Bilateral breast cancer
• Have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes
• Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy
• Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy
• Treatment with any investigational drug within 28 days prior to randomization
• Serious cardiac illness or medical conditions
• Inadequate bone marrow function
• Impaired liver function
• Inadequate renal function with serum creatinine >1.5X upper limit of normal (ULN)
• Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders)
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis
• Concurrent, serious, uncontrolled infections, or known infection with HIV
• Known hypersensitivity to study drugs, excipients, and/or murine proteins
• Current chronic daily treatment with corticosteroids (dose >10 milligrams [mg] methylprednisolone or equivalent excluding inhaled steroids)
• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, colon, skin, and/or non-melanoma skin carcinoma
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome