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,  Invasive Lobular Breast Carcinoma ER+ Breast Cancer HER2-negative Breast Cancer Female 2. Age ≥ 18 years 3. Histological diagnosis of invasive lobular breast adenocarcinoma that is ER+, and HER2 as per the updated American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines according to local testing. 4. Multifocal unilateral or bilateral breast adenocarcinoma tumours are allowed if all tested foci are lobular, ER+ and HER2- ER positive (ER+ is defined as having an IHC of 1% or more and/or an Allred of 3 or more and HER2-) HER2 negative (HER2 is defined as having an IHC of 0 or 1+ without ISH OR IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells [without IHC]); 5. A primary non metastatic or locally advanced tumour of 15 mm or more, cN0 or cN1 without prior treatment candidate for preoperative treatment. 6. ECOG Performance Status (PS) 0 or 1. 7. Adequate Bone Marrow Function including Absolute Neutrophil Count (ANC) ≥1500/μL or ≥1.5x109/L Platelets ≥100000/μL or ≥100 x 109/L Haemoglobin ≥ 9 g/dL. 8. Adequate Renal Function including: o Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml/min as calculated using the method standard for the institution. 9. Adequate Liver Function, including all of the following parameters Total serum bilirubin ≤ 2.0 x ULN unless the subject has documented Gilbert syndrome  Clinical T4 disease including inflammatory breast cancer and/or cN3. 2. Prior history of invasive cancer in the past 5 years except basal or squamous cell carcinoma of skin that has been definitively treated. 3. Known hypersensitivity to the study drugs or excipients. 4. Any illness or medical condition that is unstable or could jeopardize the safety of the subject or her compliance with study requirements. 5. Subjects unable to swallow oral medications. 6. Prior intake of letrozole, any ROS1 inhibitor, any TRK inhibitor or anticancer therapy (including endocrine therapy). 7. Concurrent treatment with strong or moderate CYP3A inhibitor. 8. Concurrent treatment with any of the drugs not permitted, i.e. strong CYP3A inducers and drugs known to cause QTc interval prolongation. 9. LVEF ≤ 55% measured by echo or MUGA 10. QTc exceeding 450 msec, history of prolonged QTc interval prolongation; risk factors for torsade de pointes; other concomitant medications that may prolong QTc; family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP). 11. Pregnant or lactating women. 12. Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis 13. Peripheral neuropathy ≥ Grade 2 14. Active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption. criterion applicable to France only 14. Vulnerable persons according to the article L.1121-6 of the CSP, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP