['breast neoplasms']
['trastuzumab', 'pertuzumab', 'palbociclib', 'fulvestrant']

        Inclusion Criteria:

          1. Female patients aged 18 years or older with tumors suitable for neoadjuvant treatment

          2. Early (> 1.5 cm) or locally advanced untreated breast cancer

          3. Histologically confirmed invasive unilateral breast cancer

          4. HER2 status to be centrally confirmed (HER2 3+ of neu amplified for cohorts A and B;
             HER2 1+/2+ without amplification for cohort C)

          5. Positive estrogen receptor (ER) > 10% and known progesterone receptor (PgR). Note: PgR
             assessment must be positive for cohort C

          6. Ki67 > 20% for cohort C

          7. Available paraffin-embedded tumor block taken at diagnostic biopsy for central
             retrospective confirmation of HER2 and ER eligibility and for assessment of Ki67 value
             and apoptosis is mandatory

          8. All patients must agree to provide tumor tissues for centralized assessment of KI67
             values and apoptosis at the required timelines (2 weeks from starting protocol therapy
             and at surgery)

          9. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1

         10. Written informed consent to participate in the trial (approved by the Institutional
             Review Board/ Independent Ethics Committee) obtained prior to any study specific
             screening procedures

         11. Willing and able to comply with the protocol

        Exclusion Criteria:

          1. Evidence of bilateral invasive breast cancer or metastatic disease (M1)

          2. Pregnant or lactating women.

          3. Women with childbearing potential unless (1) surgically sterile or (2) using adequate
             measures of contraception

          4. Previous treatment with chemotherapy, hormonal therapy or an investigational drug for
             any type of malignancy

          5. Previous extensive radiotherapy

          6. Previous investigational treatment for any condition within 4 weeks of registration
             date

          7. Known hypersensitivity reaction to one of the compounds or incorporated substances
             used in this protocol

          8. Previous or concomitant malignancy of any other type that could affect compliance with
             the protocol or interpretation of results.

          9. Other serious illness or medical condition including: history of documented congestive
             cardiac failure; angina pectoris requiring anti-anginal medication; evidence of
             transmural infarction on ECG; poorly controlled hypertension; clinically significant
             valvular heart disease; high-risk uncontrolled arrhythmias

         10. Baseline left ventricular ejection fraction (LVEF) < 55% by echocardiography or
             multi-gated scintigraphic scan (MUGA)

         11. QTc (corrected QT interval) >480 msec or a family or personal history of long or short
             QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de
             Pointes (TdP)

         12. Patients with a history of uncontrolled seizures, central nervous system disorders or
             psychiatric disability judged by the investigator to be clinically significant and
             precluding informed consent or adversely affecting compliance with study drugs

         13. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes
             mellitus

         14. Current use or anticipated need for food or drugs that are known strong CYP3A4
             (cytochrome P450 3A4) inhibitors or inducers

         15. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging
             drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)

         16. Abnormal baseline hematological values:

         17. Abnormal baseline liver function, bilirubin, creatinine and/or INR (international
             normalized ratio)
      