• First disease progression under tucatinib-capecitabine-trastuzumab. OR Medical contra-indication to initiate or continue capecitabine in association with tucatinib-trastuzumab (investigator's decision based on patient medical history, DPD deficiency and/or capecitabine grade 2 toxicity or higher).

• Age \> 18 years,

• Histologically confirmed HER2+ breast carcinoma (ASCO/CAP guidelines) with archived tumor tissue available,

• Have a life expectancy of at least 3 months,

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,

• Participants must be able to swallow capsules,

• Participants must be able and willing to be available for the duration of the study and are willing to follow study procedures,

• Measurable disease, assessed by RECIST version 1,

• Patients with brain metastases are eligible:

‣ Unless urgent treatment is required

⁃ If time since WBRT is ≥ 21 days prior to first dose of treatment, time since SRS is ≥ 7 days prior to first dose of treatment, or time since surgical resection is ≥ 28 days

⁃ Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

⁃ Left ventricular ejection fraction (LVEF) ≥ 50% (within 4 weeks before inclusion)

⁃ Adequate organ function (obtained within 14 days prior to treatment start) as evidenced by:

⁃ o Absolute neutrophil count (ANC) ≥ 1.5 X 10\^9/L

⁃ o Hemoglobin (Hgb) ≥ 9 g/dL

⁃ o Platelet count ≥ 100 X 10\^9/L

‣ Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with a documented history of Gilbert's disease (≤ 2 X ULN)

‣ Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5 X ULN (for patients with liver metastases ≤ 5 X ULN);

‣ Alkaline phosphatase (AP) ≤ 3 X ULN (for patients with liver metastases, ≤ 5 X ULN);

‣ Serum creatinine ≤ 1.5 mg/dL (133 μmol/L) or calculated creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula).

⁃ If the patient is female:

∙ Women of childbearing potential (WCBP): negative serum pregnancy test. The patient must be willing to use effective methods of contraception. Patients must be postmenopausal, surgically infertile, or willing to use a physical barrier method of contraception in addition to an intrauterine device or hormonal contraception until at least 6 months after completion of study treatment,

∙ If the patient is male:

∙ Male patients must agree to use an acceptable method of contraception (e.g., condom) during the study and for 3 months after completion of investigational treatment, 14. Patients must be covered by a health insurance plan. 15. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.