• Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.

• Female or male patients ≥ 18 years of age at the time of signing ICF.

• Radiologically documented metastatic breast cancer with locally documented HER2-low status according to the 2018 ASCO/CAP guidelines.

• Life expectancy ≥ 12 weeks.

• Karnofsky Performance Status (KPS) ≥70%, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.

• Participants with contraindications to T-DXd therapy cannot be enrolled to the study.

• Newly diagnosed or progressive BM without indication for immediate local therapy.

• Measurable disease by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.

• Presenting with one of the following:

‣ ≥1 brain lesion, measurable (≥10 mm per local radiological assessment) or;

⁃ Patients may or may not have untreated type II LMD per European Association of Neuro-Oncology (EANO)- European Society for Molecular Oncology (ESMO) criteria.

⁃ Patients must have undergone ≥1 line of systemic treatment in the advanced setting.

⁃ Patients have adequate treatment washout period before enrolment, defined as:

∙ local therapy (major surgery and radiotherapy) or antibody treatment ≥4 weeks;

‣ targeted agents, chemotherapy, small molecule, or anti-cancer hormonal therapy ≥3 weeks.

⁃ Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrolment.

⁃ Patient has adequate bone marrow, liver, renal and coagulation function:

∙ Hematological: without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within 7 days before first study treatment dose.

‣ Hepatic: Serum albumin ≥ 2.5 g/dL; total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 in patients with liver metastases or know history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN (≤ 5 in patients with liver metastases); international normalized ratio (INR) \< 1.5.

‣ Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 based on Cockcroft-Gault glomerular filtration rate estimation for patients with creatinine levels above institutional normal.

⁃ Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0). Participants with chronic Grade 2 toxicities may be eligible per the discretion of the investigator.

⁃ Note: Except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion.

⁃ For women of childbearing potential: agreement to remain abstinent (must refrain from heterosexual intercourse) or use highly effective contraceptive methods, or two effective contraceptive methods, as defined in the CSP, during the treatment period and for at least 7 months after the last dose of study treatment, whichever is longer. Women of childbearing potential must have a negative serum pregnancy test within 14 days before study treatment initiation and must agree to refrain from donating eggs during the entire study treatment period and for 7 months after the last administration of the study drug.

⁃ Being male subjects, surgically sterile or having agreed with true abstinence (must refrain from heterosexual intercourse), or whose female partners are willing to agree with true abstinence or use barrier contraceptive measures mentioned above during the entire study treatment period and for 4 months after the last administration of the study drug. Males must agree to refrain from donating sperm during the entire study treatment period and for 4 months after the last administration of the study drug.

⁃ Patients must be able to tolerate therapy.

⁃ Patients must be accessible for treatment and follow-up.