Chemotherapy-Free pCR-Guided Strategy With Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer

Exclusion Criteria

• •Any patient meeting ANY of the following criteria will be excluded from the study:
• •1. Any previous treatment, including chemotherapy, anti-HER2 therapy, radiation therapy, or ET for invasive breast cancer (except for breast carcinoma in situ of the contralateral breast cancer, in the last five years before treatment initiation in this study).
• •2. HER2 disease with IHC score 0, 1+ or 2+ and in situ hybridization (ISH) positive result.
• •3. Evidence of metastatic disease. Note: All patients must be willing to undergo chest and pelvis computed tomography (CT)/MRI scan before enrolment to prove no evidence of metastatic disease. Bone scan will be performed at baseline only if there is suspicion of bone metastases. If a bone scan cannot be performed, an alternative is PET/CT using 18F-labeled sodium fluoride (18F-fluoride PET/CT).
• •4. Patients with bilateral breast cancer.
• •5. Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
• •6. History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma.
• •7. Uncontrolled hypertension (systolic \> 150 mm Hg and/or diastolic \> 100 mm Hg) despite adequate antihypertensive treatment.
• •8. Serious cardiac illness or medical conditions including, but not confined to, the following:
• •* History of NCI CTCAE v5.0 Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II.
• •* High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia \[ventricular tachycardia\], or higher-grade atrioventricular \[AV\]-block, such as second-degree AV-block Type 2 \[Mobitz II\] or third-degree AV-block).
• •* Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication.
• •* Angina pectoris requiring anti-angina medication.
• •* Clinically significant valvular heart disease.
• •* Evidence of transmural infarction on electrocardiogram (ECG).
• •* Evidence of myocardial infarction within the last 12 months prior to study entry.
• •9. History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction \[LVSD\], 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.
• •10. Active uncontrolled infection at the time of enrollment.
• •11. Current known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
• •12. Patients with pulmonary disease requiring continuous oxygen therapy.
• •13. Grade ≥2 neuropathy as per National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v)5.0.
• •14. Previous history of bleeding diathesis.
• •15. Patient is currently receiving chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed).
• •16. Major surgical procedure or significant traumatic injury within 14 days prior to study entry or anticipation of need for major surgery within the course of the study treatment.
• •17. Any other concurrent severe and/or uncontrolled medical condition that would contraindicate patient participation in the clinical study.
• •18. History of having received any investigational treatment within 28 days prior to study entry.
• •19. Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol.