Pembrolizumab and Doxorubicin Hydrochloride or Anti-Estrogen Therapy in Treating Patients With Triple-Negative or Hormone Receptor-Positive Metastatic Breast Cancer

Inclusion Criteria

• Patients with 1) stage IV metastatic triple negative breast cancer (triple negative is defined as estrogen receptor [ER] and progesterone receptor [PgR] status is 1% of tumor cell nuclei are immunoreactive for ER or PgR and HER2 statis is FISH negative or IHC - or 1+)
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease based on RECIST 1.1
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained in defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine = = 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]); creatinine clearance should be calculated per institutional standard
• Left ventricular ejection fraction by multigated acquisition scan (MUGA) or echocardiogram >= 55% for patients with triple negative breast cancer; >= upper limit of institutional normal for patient with HR+ breast cancer
• Serum total bilirubin = 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = = 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) = = 12 months (if = 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Subjects currently on a bisphosphonate or denosumab are eligible for study therapy

Exclusion Criteria

• Cohort 1: Has triple negative breast cancer, is considered for cohort 1 participation, and received prior anthracycline therapy
• Cohort 2: Has received prior aromatase inhibitor therapy and is deemed to be resistant to all three (anastrozole, letrozole, exemestane) approved AIs; resistance is defined as progression within 12 months or while on an AI
• Patient is premenopausal (medical ovarian suppression is allowed); is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Suboptimal cardiac function as defined by decreased left ventricular ejection fraction < 55% for cohort 1, and < 50% for cohort 2
• Prior pembrolizumab
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention pr