Functional Precision Oncology to Predict, Prevent, and Treat Early Metastatic Recurrence of TNBC

Registration: Pre-tumor Collection Eligibility Participant Inclusion Criteria * Subject aged ≥ 18 years. * Subject has Stage I-III disease. * Histologically or cytologically confirmed invasive breast carcinoma that is triple negative (TNBC) or hormone receptor (HR)-low/Her2 negative --TNBC is defined as: * HER2 expression 0 or 1+ on immunohistochemistry (IHC) or non-amplified (defined as HER2/CEP17 ratio \<2 or copy number \<6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, non-amplified HER2 expression must be confirmed by FISH. Pathologic diagnosis of TNBC (negative HER2 status by cytogenetics, \<1% of cells stained positive for estrogen receptor (ER) by IHC, and \<1% of cells stained positive for progesterone receptor (PR) by IHC). --HR-low/Her2(-) is defined as: * HER2 expression 0 or 1+ on IHC or non-amplified (defined as HER2/CEP17 ratio \<2 or copy number \<6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, non-amplified HER2 expression must be confirmed by FISH.1-10% of cells stained positive for ER by IHC, and/or 1-10% of cells stained positive for PR by IHC). * Primary tumor OR local lymph node metastasis that is ≥ 1.5 cm. Patients with inflammatory breast cancer are eligible, regardless of tumor size. Patients with multifocal or multicentric breast cancer are eligible so long as ALL tumors biopsied per standard of care guidelines and/or investigator discretion meet receptor status criteria, and at least one tumor measures ≥ 1.5 cm. * Patient is considered for preoperative cytotoxic chemotherapy per standard of care or in the context of a separate, ongoing clinical trial. * Patient has not received any prior therapy for thier breast cancer. * Willing and capable (per treating investigator's assessment) to undergo baseline tumor material collection from the primary tumor or lymph node metastasis. * 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 tumor material 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 ≥ 12 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. * No prior history of local or locally advanced hormone receptor positive (ER and/or PR expression \>10% on immunohistochemistry) breast cancer, unless the following conditions are met: * All treatment with curative intent has been completed, except adjuvant medical non-chemotherapy treatments (e.g. adjuvant endocrine therapy with any hormonal agent and/or CDK4/6 inhibitors), AND * An interval of ≥6 months has elapsed between completion of these treatments and histologic diagnosis of eligible breast cancer. 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. If care has been transferred to a new physician while the patient is on-study, physician is the treating medical oncologist for the patient who met all of the inclusion criteria and none of the exclusion criteria at the time of patient study enrollment. * 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. Participant Exclusion Criteria * Evidence of metastatic breast cancer * ER and/or PR expression \>10% on immunohistochemistry * Her2(+) and/or Her2-amplified breast cancer. HER2 expression 3+ on IHC or amplified (defined as HER2/CEP17 ratio ≥2 or copy number \>6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, reflex FISH must be performed to determine eligibility. * Patient has bilateral breast cancer * Patient received any anti-cancer therapy or any investigational therapy prior to study entry and collection of tumor. --Treatment includes: neoadjuvant therapy, radiation therapy, chemotherapy, bisphosphonates for an indication other than osteopenia/osteoporosis, and/or hormonal therapy administered for the currently diagnosed primary breast cancer prior to study entry. Hormonal therapy for a prior diagnosis of a hormone receptor-positive breast cancer us allowed. * The diagnosis of another malignancy, unless the patient is considered disease-free for ≥5 years before study entry. Patients are eligible if diagnosed and treated for car