SOC Chemotherapy +/- Tocilizumab for Triple Negative and ER-low Breast Cancers

Inclusion Criteria:

1. ≥ 18 years old at the time of informed consent

2. Ability to provide written informed consent and HIPAA authorization

3. Locally recurrent (not amenable to local therapy with curative intent) or metastaticbreast cancer that is triple negative or ER-low (ER and PR ≤ 9% weak staining)

4. Zero or one prior chemotherapy for metastatic disease a. Prior (neo)adjuvant therapy will be considered one line of therapy for metastaticdisease in patients who recur while on or within 12 months of completion of (neo)adjuvant therapy.

5. Planned standard of care chemotherapy based on NCCN guidelines.

6. Single agent therapy is preferred but use of combination regimens consideredSOC by NCCN is allowed.

7. Chemotherapy delivered via a SOC antibody-drug conjugate is allowed but ADCsmay not be used in combination with other agents.

8. Patients with tumors that are PD-L1+ (CPS > 10) must have had prior exposure to animmune checkpoint inhibitor in the metastatic setting.

9. Patients who received (neo)adjuvant IO therapy and progress while on or within 12 months of completion of (neo)adjuvant IO therapy may participate withoutadditional IO treatment.

10. Patients with major contraindications to immune therapy, may participatewithout IO exposure regardless of PD-L1 status in the first line setting.

11. PD-L1 status is not required for patients in the second line setting.

12. Measurable disease based on RECIST 1.1 criteria.

13. Disease amenable to and consent for study-specific biopsy NOTE: If no diseaseamenable to biopsy is present at the time of second biopsy, subjects may continueparticipation in the study and further study specific biopsies will not be required.

14. ECOG PS 0 or 1

15. Patients with treated, asymptomatic CNS disease may participate if the patient is > 4 weeks from completion of CNS therapy (radiation and/or surgery), is clinicallystable at the time of study entry, and is receiving stable or decreasing dose ofcorticosteroids. Brain MRI or head CT is required at screening for patients withknown brain metastases.

16. Adequate organ function as indicated by:

17. Total bilirubin < ULN (except in patients with documented Gilbert's disease,who must have a total bilirubin < 3.0 mg/dL)

18. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 x ULN

19. Creatinine clearance of > 50 mL/min using the Cockcroft-Gault formula

20. Absolute neutrophil count (ANC) > 1.2 K/mm3

21. Platelets > 75 K/ mm3

22. Hgb > 9.0 g/dL

23. Women of childbearing potential must have a negative pregnancy test within 14 daysof protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remainingcelibate by choice) unless they meet one of the following criteria:

24. Has undergone a hysterectomy or bilateral oophorectomy; or

25. Has been naturally amenorrheic for at least 24 consecutive months.

26. Women of childbearing potential and men must agree to use effective contraceptionthroughout 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:

1. Prior treatment with or known contraindication to treatment with tocilizumab orother IL-6/IL-6R targeted agent

2. Active infection requiring parenteral antibiotics

3. Concurrent use of methotrexate or systemic corticosteroids other than stable ordecreasing doses for management of CNS involvement

4. Active or symptomatic CNS disease

5. Patients with HER2+ disease Note: HER2 will be considered positive if scored 3+ byimmunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situhybridization (FISH) ratio of > 2.0 or > 6 total HER2 gene copies per cell.

6. Patients with active malignancy other than breast cancer. Patients with priormalignancies without recurrence after standard treatment will not be excluded

7. Radiation therapy within 2 weeks of registration

8. Hormone therapy within 2 weeks of registration

9. Planned treatment with Olaparib or other PARP inhibitor.