Decreasing Treatment for Metastatic HER2-Positive Breast Cancer With Undectable Cancer Levels in Blood Tests.

Inclusion Criteria: 1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent; 2. Men or women ≥18 years of age; 3. Documented diagnosis of locally advanced inoperable or metastatic histologically-proven HER2-positive breast cancer (HER2-positive is defined as HER2 3+ immunohistochemical overexpression, or the presence of HER2 amplification, according to ASCO-CAP guidelines); 4. Must have an adequate archival tumor tissue sample available for next-generation sequencing (NGS) analysis by central laboratory, in order to design the ctDNA test (based on most recent available tumor tissue sample, metastatic biopsy (bone tissue excluded) and primary tumor authorised); 5. Patient with Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) ≤1; 6. Patient must have received continuous anti-HER2 targeted therapy (including Trastuzumab, Trastuzumab/Pertuzumab, Trastuzumab-Deruxtecan or T-DM1) treatment for at least 2 years in any line setting, for their locally advanced inoperable or metastatic HER2 + breast cancer (prior treatment interruption of 3 months maximum is allowed), with complete response or partial response at last radiological assessment; Note: the number of patients who received anti-HER2 targeted therapy in second line setting or more will be capped to 50% of the overall population 7. In case of bone disease only, complete metabolic response in 18-FDG pet-scanner is required; 8. Patient with treated (surgery and/or radiation therapy) and controlled primary tumor; 9. Patients with ER-positive disease may or may not have received concomitant endocrine therapy (which must be continued if present). Concomitant ovarian blockade using Luteinizing Hormone-Releasing Hormone (LHRH) agonists is authorised as well; 10. Adequate cardiac, renal, haematological and hepatic functions according to guidelines hospital; 11. Women of childbearing potential must have a negative serum or urine pregnancy test done within 28 days before inclusion; 12. Non post-menopausal women and fertile men must agree to use adequate contraception methods during the study. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive; 13. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up; 14. Patients must be affiliated to a Social Security System (or equivalent). Exclusion Criteria: 1. Any breast cancer progression over the past 2 years or at study entry; 2. Patient concurrently using other approved or investigational antineoplastic agents than trastuzumab, pertuzumab, Trastuzumab-Deruxtecan, TDM-1 +/- endocrine therapy; 3. Had an history of tumoral meningitis or clinically active central nervous system metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms; 1. Subjects with curatively treated brain metastases (i.e., complete removal surgery or stereotactic radiotherapy) who are no longer symptomatic and do not require treatment with corticosteroids or anticonvulsants may be included in the study provided they have recovered from the acute toxicity of radiotherapy and there has been no progression of the brain metastases within the past 24 months. 2. Subjects with brain metastases only or treated with whole brain radiotherapy will be excluded of the study 4. Major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results; 5. History of any prior ipsi or contralateral breast cancer (except in case of DCIS) unless if both primary tumors were confirmed to be HER2-positive; 6. Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease and treatment for at least 3 years; 7. Major surgery within 2 weeks prior to study entry; 8. Pregnant women or women who are breast-feeding; 9. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons; 10. Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to patient enrolment and for the duration of the study); 11. Persons deprived of their liberty or under protective custody or guardianship.