-Is advanced or metastatic

-Has HER2-low expression as determined by the central laboratory result

-Was never previously reported as HER2-positiveas per American Society of Clinical Oncology/College of American Pathologists guidelines

-Is documented as HR+

-Must have an adequate tumor tissue sample available for assessment of HER2 by central laboratory, preferably in formalin fixation and paraffin embedding (FFPE) blocks based on a mandatory FFPE tumor sample obtained at the time of metastatic disease or later

-Eastern Cooperative Oncology Group performance status of 0 or 1

-Must have had either: Disease progression on endocrine therapy within 6 months of starting 1st line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator, OR Disease progression on at least 2 previous lines of ET with or without a targeted therapy administered for the treatment of metastatic disease

-No prior chemotherapy for advanced or metastatic breast cancer. Subjects who have received chemotherapy in the neo-adjuvant or adjuvant setting are eligible, as long as they have had a disease-free interval

-Life expectancy at least 12 weeks at screening

-Subjects must have at least 1 measurable lesion or have non-measurable, bone-only disease that can be assessed by computer tomography or Magnetic Resonance Imaging or X-Ray.

-Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 7 months after the last dose of study treatment

-Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening and throughout the duration of the study treatment and the washout period

-Ineligible for all options in the investigator's choice chemotherapy arm

-Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events or compromise the ability of the subject to give written informed consent

-Clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to the randomization

-Uncontrolled or significant cardiovascular disease

-Has as a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis(pna) that required steroids, has current ILD/pna, or where suspected ILD/pna cannot be ruled out by imaging at screening

-Subjects with prior use of immunosuppressive medicatiowithin 14 days prior to first study dose, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses less than 10 mg/day of prednisone or equivalent

-Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade at least 1 or baseline

-Previous treatment with anti-HER2 therapy

-Prior treatment with antibody-drug conjugate that comprised an exatecan derivative that is a topoisomerase I inhibitor

-Prior randomization or treatment in a previous DB-1303/BNT323 study regardless of treatment assignment