Patient description: The patient is a 42 year-old postmenopausal woman who had a screening sonogram which revealed an abnormality in the right breast. She had no palpable masses on breast exam. Core biopsy was done and revealed a 1.8 cm infiltrating ductal breast carcinoma in the left upper outer quadrant. Lumpectomy was done and the surgical margins were clear. The tumor was HER2-positive and ER/PR negative. Axillary sampling revealed 1 positive lymph node out of 12 sampled. CXR was unremarkable. She is using “well women” multivitamins daily and no other medication. She smokes frequently and consumes alcohol occasionally. She is in a relation with only one partner and has a history of 3 pregnancies and live births. She breastfed all three children.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Breast Cancer Written informed consent prior to beginning specific protocol procedures. 2. Female or male patients ≥ 18 years of age. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4. Histologically proven invasive breast cancer. 5. Operable breast cancer (cT1-3 and/or cN0-2 tumors) (breast cancer TNM classification) 6. Tumor size larger than or equal to 1.5 centimeter (cm) in diameter by magnetic resonance imaging (MRI) or ultrasound with a significant 18F-FDG uptake defined as maximum standarized uptake value (SUVmax: maximum standarized uptake value) ≥1.5 x SUVmean (mean standarized uptake value) liver + 2 SD (standard deviation. Multicentric/multifocal tumors will be allowed only if: 1. Histological confirmation of at least two lesions. 2. All tumors must be HER2-positive. 3. Largest lesion must be larger than or equal to 1.5 cm in diameter by MRI or ultrasound. 7)Centrally confirmed HER2-positive disease according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria. 8)Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry. Patient has adequate bone marrow, liver, and renal function: 9)Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 10.0 g/dL (≥ 6.2 mmol/L). 10)Hepatic: total bilirubin ≤ institutional upper limit of normal (ULN) (except for Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 times ULN. 11)Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. 12)Patient must be accessible for treatment and follow-up  Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer. 2. cT4 and/or cN3 tumors (TNM breast cancer classification) 3. Bilateral breast cancer. 4. Evidence of metastatic disease by routine clinical assessment chest x-ray, liver ultrasound, and bone scan; or computed tomography (CT) scan of thorax and abdomen and bone scan, except patients with subclinic M1 (metastases) at baseline only according to 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) that will be allowed to be included into cohort C. 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. Left ventricular ejection fraction (LVEF) below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO). 8. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment. 9. Clinically significant cardiovascular disease [stroke, unstable angina pectoris, or documented myocardial infarction within six months prior to study entry; history of documented congestive heart failure (CHF) (New York Heart Association II-III-IV); symptomatic pericarditis; documented cardiomyopathy; ventricular arrythmias with the exception of benign premature ventricular contractions; conduction abnormality requiring a pacemaker; other arrhythmias not controlled with medication]. 10. Active uncontrolled infection at the time of enrollment. 11. Current known infection with HIV, hepatitis B virus, or hepatitis C virus. 12. Patients with pulmonary disease requiring continuous oxygen therapy. 13. Previous history of bleeding diathesis. 14. Patient is currently receiving anti-coagulant therapy, chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed). 15. Major surgical procedure or significant traumatic injury within 14 days prior to randomization or anticipation of need for major surgery within the course of the study treatment. 16. Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the investigator´s judgment, contraindicate her participation in the clinical study. 17. Concurrent participation in other clinical trial, except other translational studies. 18. History of receiving any investigational treatment within 28 days prior to randomization. 19. Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol. LINGain sub-study: The project intends to a total of 126 blood samples from PHERGain trial, as follows: 105 from patients treated with trastuzumab and pertuzumab ± endocrine therapy (according to HR status); 21 from patients treated with trastuzumab and pertuzumab + carboplatin and docetaxel