Functional Precision Oncology for Metastatic Breast Cancer

Inclusion Criteria:

* Male or female subject aged ≥ 18 years.
* Her2 negative on immunohistochemistry or nonamplified breast cancer
* Metastatic or recurrent unresectable breast cancer:

  * Patient with triple-negative breast cancer without prior treatment in the metastatic setting.
  * OR
  * Patient with hormone receptor-positive breast cancer that has exhausted or refused all endocrine monotherapy or endocrine therapeutic combinatorial options AND has not yet been treated with chemotherapy in the metastatic settings, but for whom chemotherapy is indicated.
* Willing and capable (per treating investigator's assessment) to undergo baseline tumor collection. Tumor collection may include a solid tumor tissue sample or a fluid sample containing tumor cells.
* Patient can safely undergo tumor collection:

  * The tumor is reasonably accessible to tumor collection;
  * The tumor is amenable to tumor collection, e.g. does not abut neurovascular structures;
  * If the patient receives anticoagulation, anticoagulation can be safely withheld to accommodate for tissue acquisition;
  * The patient does not have a medical condition that would render tumor acquisition a high-risk procedure, (e.g. tumor material acquisition from lung metastases in a patient with emphysema).
* Life expectancy of ≥ 6 months as assessed by the treating investigator.
* ECOG Performance Status ≤ 2.
* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  * Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have estradiol and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  * Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
* At least one lesion (measurable or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment by computed tomography (CT), magnetic resonance imaging (MRI), plain X-ray, or physical examination.

Exclusion Criteria:

* Diagnosis of any other malignancy with a life expectancy of \< 5 years.
* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

  * Myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (\> New York Heart Association Classification Class IIB) or a serious cardiac arrhythmia requiring medication.
  * Renal or liver disease that prohibits the patient from receiving at least single-agent full recommended dose chemotherapy.
* The patient cannot safely undergo tumor collection for reasons including but not limited to:

  * Tumor is inaccessible;
  * The patient requires anticoagulation which cannot be withheld;
  * The patient has bleeding diathesis;
  * Any other reason that would render tumor tissue acquisition a high-risk procedure.
* Patient cannot or is unwilling to receive chemotherapy
* Known brain metastases or cranial epidural disease. Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before Step 1 Registration for study will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the Step 1 Registration for study.
* Patient's only site amenable to tumor collection to generate organoids is hepatic metastases.

Physician Inclusion Criteria

* Physician is the treating medical oncologist for a patient who meets all of the inclusion criteria and none of the exclusion criteria.
* Willing and able to answer the physician questionnaires at the protocol required time points.
* Willing and able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Organoid Development and Tumor Material Testing Patient Eligibility

* Patient continues to meet step 1 registration criteria.
* Successful acquisition of a solid tumor biopsy sample containing ≥ 20% tumor content, or malignant fluid sample (e.g. pleural or pericardial effusion or ascites) confirmed to contain malignant cells.
* Sufficient material for Tempus commercial genomics testing and Welm lab genomics from the tumor collection; or sufficient archival tissue for Tempus and Welm lab genomics; or blood sample as allowed for liquid biopsy commercial assay.
* Sample from tumor collection is the type of sample that is feasible for organoid development as determined by the investigator.