Capecitabine Compared to Endocrine Therapy for the Treatment of Non-luminal A Hormone Receptor-Positive Metastatic Breast Cancer

Inclusion Criteria

• Signed and dated written informed consent.
• Subjects >= 18 years of age at time of signing informed consent; only participants who were born female.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Clinical stage IV invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is: * Estrogen receptor (ER) (>/= 1%) and/or progesterone receptor (PR) (>/=1%) by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) negative (by IHC or fluorescence in situ hybridization [FISH]).
• Previously exposed to: * Aromatase inhibitor (AI) + CDK4/6 inhibitor, OR * A selective estrogen-receptor modulator/ downregulator (SERM; SERD) + a CDK4/6 inhibitor.
• Prior radiation permitted (if completed at least 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity (≤ grade 1) induced by this treatment (except for alopecia). Patients with brain metastasis secondary to breast cancer and clinically stable for more than 4 weeks from completion of radiation treatment and off steroids
• Evaluable disease (measurable or non-measurable). * Measurable disease ie, at least 1 measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation). * Patients with bone only disease allowed if possible to evaluate on radiological exams (eg. bone scan, PET/CT, CT, magnetic resonance imaging [MRI]) even if lesions are non-measurable according to RECIST 1.1.
• Absolute neutrophil count (ANC) >= 1.5 × 10^9/L.
• Platelets >= 100 × 10^9/L.
• Hemoglobin >= 8g/dL (may have been transfused).
• Total serum bilirubin =< 1.5 times upper limit of normal (ULN).
• Aspartate aminotransferase (AST/ serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT/ serum glutamic-pyruvic transaminase [SGPT]) =< 2.5 × ULN (or =< 5 × ULN if liver metastases are present).
• Serum creatinine =< 1.5 x ULN or estimated creatinine clearance >= 50 mL/min as calculated using the Cockcroft-Gault (CG) equation.
• FOR RANDOMIZED PATIENTS ONLY: tumors must be diagnosed as non-Luminal A using the Blueprint registered trademark and Mammaprint registered trademark tests.
• Prior radiation permitted (if completed at least 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity (< grade 1) induced by this treatment (except for alopecia). * Patients with brain metastasis secondary to breast cancer and clinically stable for more than 4 weeks from completion of radiation treatment and off steroids

Exclusion Criteria

• Prior chemotherapy in the metastatic setting.
• Previous malignant disease other than breast cancer within the last 2 years with associated competing risk, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment).
• Persisting symptoms related to prior therapy that has not reduced to grade 1 [National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0]; however, menopausal symptoms, alopecia, and sensory neuropathy grade =< 2 is acceptable.
• Pregnant or breastfeeding females.