A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)

Inclusion Criteria: * Female participants, who are at least 18 years of age on the day of signing informed consent with newly histologically locally confirmed diagnosis of HER2neu 2+ or 3+ breast cancer. * Have previously untreated, non-metastatic (M0) HER2-enriched breast cancer defined as the following combined primary tumor (T) and regional lymph node (N) staging per American Joint Committee on Cancer (AJCC) for breast cancer staging criteria version 7 as assessed by the Investigator based on radiological and/or clinical assessment: T1c, N0-N2; T2, N0-N2; T3, N0-N2 * Patients with HER2-enriched, estrogen and/ or progesterone receptor positive or negative breast cancer defined by American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines can be included. * Availability of tumor imaging performed within three months prior to start of screening phase: breast ultrasound and computed tomography (CT) thorax/abdomen or chest X-ray/liver ultrasound, bone scan, mammography or breast magnetic resonance imaging (MRI) (according to local standard). * Ability to provide archived tumor tissue sample or at least two newly obtained separate tumor cores from the primary tumor or excisional biopsy of a tumor lesion not previously irradiated at screening to the central laboratory. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred over slides. Newly obtained biopsies are preferred over archived tissue. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut. Patients are eligible to be included in the trial only if all of the following criteria apply \[items 1-6 must be met by the patient to be enrolled into the trial and before the start of the screening phase\]: 1. Female patients, who are at least 18 years of age on the day of signing informed consent, with newly histologically locally confirmed diagnosis of HER2neu 2+ or 3+ breast cancer. 2. Previously untreated, non-metastatic (M0) HER2-enriched breast cancer defined as the following combined primary tumor (T) and regional lymph node (N) staging per AJCC for breast cancer staging criteria version 7 as assessed by the investigator based on radiological and/or clinical assessment: * T1c, N0-N2; * T2, N0-N2; * T3, N0-N2. 3. Patients with HER2-enriched, estrogen and/or progesterone receptor-positive or -negative breast cancer defined by ASCO/CAP guidelines. 4. Availability of tumor imaging performed within three months prior to start of screening phase: breast ultrasound and CT thorax/abdomen or chest X-ray/liver ultrasound, bone scan, mammography or breast MRI (according to local standard). 5. Ability to provide an archived tumor tissue sample or at least two newly obtained separate tumor cores from the primary tumor or excisional biopsy of a tumor lesion not previously irradiated at screening to the central laboratory. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred over slides. Newly obtained biopsies are preferred over archived tissue. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut. 6. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and if at least one of the following conditions applies: 1. not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR 2. a WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 7 months after the last dose of study treatment Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient. 7. The patient provides written informed consent for participation in the trial. The patient may also provide consent for future biomedical research. However, the patient may participate in the main trial without participating in future biomedical research. 8. Confirmed HER2neu (IHC 2+ status and amplification \[e.g. by FISH\] or IHC 3+ status) tumor identification by local pathology. 9. Confirmed HER2-enriched status by PAM50 testing. 10. Confirmed HR+ or HR- status. 11. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or borderline, a serum pregnancy test will be required. Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for the patient to start receiving study medication. 12. Left ventricular ejection fraction (LVEF) of ≥55% or ≥ institution lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening or performed in clinical routine within 6 weeks prior to first treatment allocation. 13. Normal ECG performed at screening or performed in clinical routine within 6 weeks prior to first treatment allocation. 14. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG performance status is to be performed within 10 days prior to the date of treatment initiation. 15. Adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to the start of study treatment. Exclusion Criteria: • Patients are excluded from the trial if any of the following criteria apply: 1. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g. CTLA-4, OX 40, CD137) or has participated in MK-3475 clinical trials. 2. Patient has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of study medication. Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy may be eligible. Note: If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3. Patient has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed. 4. Patient is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Patients who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. Patient should be excluded if she received an investigational agent with anti-cancer or anti-proliferative intent within the last 12 months. 5. Patient has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 6. Prior malignancy with a disease-free survival of ≤5 years before signing informed consent. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 7. Patient has a known hypersensitivity to the components of the study therapy, its analogs, murine proteins or any of the excipients. 8. Patient has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 9. Patient has a significant cardiovascular disease, such as: * LVEF \<55% * History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the past 6 months * Congestive heart failure (CHF) New York Heart Association (NYHA) Class I-IV or history of CHF NYHA class III or IV 10. Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the trial, including but not confined to: * Unstable arrhythmias requiring treatment, i.e., atrial tachycardia with a heart rate ≥100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block * Angina pectoris within the last 6 months requiring anti-anginal medication * Clinically significant valvular heart disease * Evidence of myocardial infarction on electrocardiogram (ECG) * Poorly controlled hypertension (e.g. systolic \>180 mm Hg or diastolic \>100 mm Hg). 11. Inadequate organ function including but not confined to: * hepatic impairment (Child Pugh Class C) * pulmonary disease (severe dyspnea at rest due to complications of advanced malignancy or requiring oxygen therapy). 12. Patient has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 13. Patient has an active infection requiring systemic therapy. 14. Patient has a known history of human immunodeficiency virus (HIV), hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (defined as detectable HCV RNA \[qualitative\] is detected). Note: Testing of hepatitis B is required in all patients during screening as standard of care according to current guidelines in early breast cancer. HIV and hepatitis C testing is required in all patients with significant risk factors (see checklist below). There is a significant risk if one of the items on the checklist applies for the patient. * HIV and hepatitis C risk checklist: * Patient has frequently changing sexual partners. * Patient practices anal sex. * The patient has already been diagnosed with another sexually transmitted infection, such as syphilis or gonorrhea. * Patient suffers from drug abuse. * Tattoos or piercings abroad within the last 4 months. * Presence of a positive HIV and/or Hepatitis C test. * Patient received a blood transfusion before 1992. * Patient is an organ transplant recipient. * The patient's mother has/had HIV and/or hepatitis C. * Patient has elevated liver blood values (relevant for hepatitis C risk). 15. Patient has a known history of active TB (Bacillus Tuberculosis). 16. Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. 17. Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 18. Patient is pregnant or breastfeeding, or expecting to conceive children or planning to breastfeed within the projected duration of the trial, starting with the screening visit through 7 months after end of treatment. 19. Male patients with breast cancer. 20. History of breast cancer. 21. Factors indicating risk of poor compliance. 22. Pathological laboratory assessments: * Thrombocytopenia \> CTCAE grade 1 * Increases in ALT/AST \> CTCAE grade 1 * Hypokalemia \> CTCAE grade 1 * Neutropenia \> CTCAE grade 1 * Anemia \> CTCAE grade 1 23. Non-operable breast cancer including inflammatory breast cancer.