A Pilot Study of a Micro-Organosphere Drug Screen Platform to Lead Care in Advanced Breast Cancer

The purpose of this study is to assess the feasibility of generating patient derived micro-organospheres (PDMO) from patients with advanced breast cancer to determine sensitivity to the most common forms of chemotherapy used in advanced breast cancer care.

The purpose of this study is to determine the feasibility of generating sufficient patient derived micro-organospheres (PDMO) from a biopsy of a patient's advanced breast cancer to determine sensitivity to the most common forms of chemotherapy used in advanced breast cancer care. While subjects are on study, they will first receive a standard of care clinical biopsy from which extra tissue is taken for research purposes. Following the biopsy, a PDMO will be generated and they will receive a chemotherapy regimen as determined by their treating physician. This study aims to enroll 15 patients. Of this 15 patient cohort we aim to enroll 5 patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) disease, 5 patients with ER+/HER2+ or ER-/HER2+ disease, and 5 patients with ER-/HER2- (TNBC) disease. There are risks to having biopsies and blood draws that may include moderate bleeding and pain at the biopsy site.

Eligibility Criteria:
Inclusion Criteria:

1. Provide written informed consent.
2. Female ages 18 or older.
3. Have measurable disease ≥ 2 cm defined by RECIST version 1.1.
4. Amenable to standard of care biopsy with co-consent to the Duke BioRepository \& Precision Pathology Center (BRPC) protocol (Pro00035974) to collect extra biopsy tissue for research or willing to provide extra tissue other than standard of care without co-consent to BRPC.
5. Evidence of advanced cancer of the breast that is surgically unresectable with pathology confirming ER, PR, and HER2 status. NOTE: patients may enroll prior to receiving clinical biopsy results based on historical pathology results.
6. Patient is eligible for chemotherapy as monotherapy or in combination with single-agent anti HER2 Therapy.

   * ER+/PR+/HER2-, must have progressed or be intolerant to CDK 4/6 inhibitor and/or endocrine therapy unless CDK 4/6 inhibitor is not able to be provided per the clinician's discretion endocrine therapy and CDK 4/6 inhibitor
   * ER+/PR+/HER2+ or ER-/PR-HER2+, must have progressed or be intolerant to ≥ 2 lines of anti-HER2 therapy and be considered for mono-chemotherapy with trastuzumab and/or anti-HER2 tyrosine kinase inhibitor
   * ER-/PR-HER2-, PD-L1- and/or TMB \<10 may may be considered for first line of treatment
7. Treating physician is planning to treat breast cancer in the advanced setting with a chemotherapy backbone. This study excludes patients who will receive an antibody-drug conjugate as their proposed treatment.
8. Impending visceral crisis is allowed only if the patient can have a biopsy prior to starting systemic mono-chemotherapy
9. ECOG performance status of 0, 1, or 2.
10. Any metastatic site that is ≥ 2cm and amenable to core needle biopsy. Patients with brain metastases are allowed and MOS may be generated from a resected breast cancer brain metastasis

Exclusion Criteria:

1. Actively requiring systemic antibiotics.
2. Clinically significant cardiac disease, including unstable angina or acute myocardial infarction within 6 months of enrollment.
3. Leptomeningeal disease
4. Pregnant women.
5. Enrolling on an investigational agent.