Inclusion Criteria:  Adults with histologically-confirmed HER3-high (75 percent of tumor cells or more express HER3), HER2 negative, unresectable locally advanced or metastatic breast cancer that HR+ is at the time of the first breast cancer diagnosis Participants with a documented radiologic unresectable or metastatic progression Participants may have received anthracyclines and taxanes as (neo) adjuvant treatment and must have received one line of chemotherapy for Advanced breast cancer (ABC), but not more than one line. Participants must have a clinically or radiologically documented evidence of tumor progression on or after cyclin dependent kinase 4/6 (CDK 4/ 6) inhibitor combined with endocrine therapy. Previous treatments with PI3K inhibitors, mTOR inhibitors, AKT-inhibitors and poly ADP ribose polymerase (PARP)-inhibitors are allowed Participants must have metastatic site easily accessible to biopsy (with exception of bone metastasis) Participants must have at least one radiologically measurable lesion (different from the biopsy site) Participants must have an ECOG PS equals to 0 or 1 Participants must have a life expectancy of 12 weeks or more Participants must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1 Females of reproductive/childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception or avoid intercourse during the study and for at least 7 months after the last dose of study drug.  Contraceptive methods considered highly effective:  Intrauterine device (IUD) Bilateral tubal occlusion Vasectomized partner Complete sexual abstinence during and upon completion of the study and for at least 7 months for females after the last dose of study drug  Female participants must not donate, or retrieve for their own use, ova from the time of screening and for at least 7 months after the final study drug administration  -If male, the participant must be surgically sterile, must withhold heterosexual intercourse, or must be willing to use a highly effective birth control upon enrollment, and for at least 4 months following the last dose of study drug  Male participants must not freeze or donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration  Participant must understand, sign, and date the written ICF prior to any protocol-specific procedures performed. Participant should be able and willing to comply with study visits and procedure as per protocol Participant must be affiliated to a social security system or beneficiary of the same  Exclusion Criteria:  Breast cancer amenable for resection or radiation therapy with curative intent Any history of interstitial lung disease (ILD), actual ILD, or a suspicion of an ILD  Clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:  Any underlying pulmonary disorder Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement OR prior pneumonectomy The use of chronic systemic corticosteroids at a dose superior to 10 mg of prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study Evidence of any leptomeningeal disease Evidence of corneal disease Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol Evidence of clinically active spinal cord compression or brain metastases defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms  Inadequate washout period prior to Cycle 1 Day 1, defined as:  a. Whole brain radiation therapy within 14 days before treatment or stereotactic brain radiation therapy, within 7 days before treatment b. Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), within 14 days before treatment or 5 half-lives, whichever is longer Immune checkpoint inhibitor therapy, within 21 days before treatment d. Endocrine therapy within 21 days of treatment e. Major surgery (excluding placement of vascular access) within 28 days of treatment f. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days or palliative radiation therapy within 14 days of treatment g. Chloroquine or hydroxychloroquine within 14 days before treatment h. Live virus vaccination, within 28 days before treatment  Prior treatment with an anti-HER3 antibody and/or ADC containing an exatecan derivative that is a topoisomerase I inhibitor Participants with a grade equals or less than 2 unresolved toxicities from previous anticancer therapy (other than alopecia) A history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of U3-1402, or to other monoclonal antibodies Any evidence of primary malignancy other than locally advanced or metastatic lung cancer within three years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated  Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day :  Corrected QT interval higher than 470 ms for females and 450 ms for males according to Fridericia's formula (QTcF) and assessed based on triplicate ECGs, approximately 1 minute apart Left ventricular ejection fraction (LVEF) less than 50% by either ECHO or cardiac MRI Resting systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg  e. Myocardial infarction within six months f. NYHA Classes 2 to 4 within 28 days before treatment g. Uncontrolled angina pectoris within six months. h. Cardiac arrhythmia requiring antiarrhythmic treatment  Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1.  Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST/ALT less than 3 ULN  Participants with a history of Hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection, is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer)  Known human immunodeficiency virus (HIV) or active COVID-19 infection Participants under guardianship or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent Female participants who are pregnant or breastfeeding or intend to become pregnant during the study Participation in another clinical trial evaluating an experimental drug (except non-interventional research) Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Participants must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1  Inadequate washout period prior to Cycle 1 Day 1, defined as:  Whole brain radiation therapy within 14 days before treatment or stereotactic brain radiation therapy, within 7 days before treatment Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), within 14 days before treatment or 5 half-lives, whichever is longer Immune checkpoint inhibitor therapy, within 21 days before treatment Endocrine therapy within 21 days before treatment Major surgery (excluding placement of vascular access), within 28 days before treatment Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation, within 28 days before treatment or palliative radiation therapy within 14 days before treatment Chloroquine or hydroxychloroquine within 14 days before treatment. Live virus vaccination, within 28 days before treatment Prior treatment with an anti-HER3 antibody and/or ADC containing an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan). Participants with grade ≤2 unresolved toxicities from previous anticancer therapy (other than alopecia), as defined by the NCI-CTCAE version 5.0 Participant with a known hypersensitivity to either the drug substances or inactive ingredients in the drug product Participant with a history of severe hypersensitivity reactions to other monoclonal antibodies Participant has any primary malignancy other than locally advanced or metastatic breast cancer within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated  Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including:  Corrected QT interval higher than 470 ms for females and 450 ms for males according to Fridericia's formula (QTcF) and assessed based on triplicate ECGs, approximately 1 minute apart Left ventricular ejection fraction (LVEF) less than 50% by either ECHO or cardiac MRI Resting systolic blood pressure higher than 140 mmHg or diastolic blood pressure higher than 90 mmHg Myocardial infarction within six months NYHA Classes 2 to 4 within 28 days before treatment Uncontrolled angina pectoris within six months. Cardiac arrhythmia requiring antiarrhythmic treatment  Participants with past or resolved hepatitis B virus (HBV) infection are eligible if:  Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST/ALT less than 3 ULN  Participants with a history of Hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection, is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer)  Female participant who is pregnant or breastfeeding or intends to become pregnant during the study Participants with human immunodeficiency virus (HIV) or active coronavirus (COVID-19) infection Participants with any psychological, familial, sociological or geographical condition potentially hindering compliance with the study protocol procedures and follow-up schedule Participants under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent. Participation in another clinical trial evaluating an experimental drug (except non-interventional research