Chemotherapy with or without Tocilizumab for the Initial Treatment of Unresectable, Locally Recurrent, or Metastatic Triple Negative or ER and PR-low Breast Cancer

Inclusion Criteria

• >= 18 years old at the time of informed consent
• Ability to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
• Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer that is triple negative or ER-low (ER and PR ≤ 9% weak staining)
• Received up to 2 prior therapies for metastatic disease * Prior (neo)adjuvant therapy will be considered one line of therapy for metastatic disease in patients who recur while on or within 12 months of completion of (neo)adjuvant therapy * Participation in this protocol as either first, second and third-line therapy is allowed
• Planned standard of care chemotherapy based on National Comprehensive Cancer Network (NCCN) guidelines * Single agent therapy is preferred but use of combination regimens considered SOC by NCCN is allowed * Chemotherapy delivered via a SOC antibody-drug conjugate is allowed but antibody-drug conjugates (ADCs) may not be used in combination with other agents
• Patients with tumors that are PD-L1+ (CPS > 10) must have had prior exposure to an immune checkpoint inhibitor in the metastatic setting * Patients who received (neo)adjuvant immuno-oncology (IO) therapy and progress while on or within 12 months of completion of (neo)adjuvant IO therapy may participate without additional IO treatment * Patients with major contraindications to immune therapy, may participate without IO exposure regardless of PD-L1 status in the first line setting * PD-L1 status is not required for patients in the second line setting
• Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Patients with treated, asymptomatic central nervous system (CNS) disease may participate if the patient is > 4 weeks from completion of CNS therapy (radiation and/or surgery), is clinically stable at the time of study entry, and is receiving a stable or decreasing dose of corticosteroid therapy. Brain MRI or head CT is required at screening for patients with known brain metastases
• Total bilirubin =< upper limit of normal (ULN) (except in patients with documented Gilbert’s disease, who must have a total bilirubin =< 3.0 mg/dL)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5.0 x ULN
• Creatinine clearance of >= 50 mL/min using the Cockcroft-Gault formula
• Absolute neutrophil count (ANC) >= 1.5 K/mm^3
• Platelets >= 100 K/mm^3
• Hemoglobin (Hgb) >= 9.0 g/dL
• Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria: * Has undergone a hysterectomy or bilateral oophorectomy; or * Has been naturally amenorrheic for at least 24 consecutive months
• Women of childbearing potential and men must agree to use effective contraception throughout the study and for 6 months after the last study treatment. Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections)

Exclusion Criteria

• Prior treatment with or known contraindication to treatment with tocilizumab or other IL-6/IL-6R targeted agent
• Active infection requiring parenteral antibiotics
• Concurrent use of methotrexate or systemic corticosteroids
• Active or symptomatic CNS disease
• Patients with HER2+ disease. HER2 will be considered positive if scored 3+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of > 2.0 or > 6 total HER2 gene copies per cell
• Patients with active malignancy other than breast cancer. Patients with prior malignancies without recurrence after standard treatment will not be excluded
• Radiation therapy within 2 weeks of registration
• Hormone therapy within 2 weeks of registration