177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer

Inclusion Criteria:

Life expectancy of > 6 months, as determined by the investigator
Ability to understand and the willingness to sign a written informed consent document
Histologically or cytologically confirmed metastatic breast carcinoma
Stage IV or recurrent disease with distant metastases
Female and male patients with breast cancer will be included in the study.
Participants must have experienced disease progression after at least two lines of standard treatment modalities and/or one prior line of cytotoxic chemotherapy (not just endocrine therapy). Specifically, patients must have received or declined the following therapies: a) HR+/HER2: endocrine therapy and CDK4/6i; b) HER2+: trastuzumab, pertuzumab, T-DM1 and tucatinib; c) TNBC: chemotherapy, immunotherapy (in PD-L1+ tumors). Patients can be consented if they are foregoing treatments known to confer survival advantage.
Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v1).1 that is amendable to biopsy
Confirmed presence of SSTR based on >50% of leisions with DOTATATE uptake of 68Ga DOTATATE equivalent to the liver.
Participants must have fully recovered from the acute toxic effects of all prior treatment to grade 1 or less, except alopecia and =< grade 2 neuropathy which are allowed
Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Participant must consent to undergo a pre-treatment screening biopsy for enrollment
Hemoglobin >= 8.0 g/dL with no blood transfusion in the past 28 days (measured within 28 days prior to administration of study treatment)
Absolute neutrophil count (ANC) >= 2.0 x 10^9/L (measured within 28 days prior to administration of study treatment)
Platelet count >= 75 x 10^9/L (measured within 28 days prior to administration of study treatment)
Total bilirubin =< 3 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (unless liver metastases are present in which case they must be =< 5 x ULN) (measured within 28 days prior to administration of study treatment)
Serum albumin >= 3.0 g/L, unless prothrombin time or international normalized ratio (INR) value is within the normal range (measured within 28 days prior to administration of study treatment)
Participants must have serum creatinine =< 1.7 mg/dL, or creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days prior to administration of study treatment)
Female participants of childbearing potential (FOCBP) must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

FOCBP agree to use a highly-effective method of contraception starting with the first dose of study therapy through up to 7 months after the last dose of study therapy

FOCBP are those who are not proven postmenopausal. Postmenopausal is defined as:

Amenorrheic for > 24 consecutive months following cessation of exogenous hormonal treatments
Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 years of age
Radiation-induced oophorectomy with last menses > 1 year ago
Chemotherapy-induced menopause with > 1 year interval since last menses
Surgical sterilization (bilateral oophorectomy or hysterectomy or tubal ligation)

Exclusion Criteria:

Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of first dose of 177Lu- DOTATATE treatment

Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device
Prior external beam radiation therapy to more than 25% of the bone marrow
Other malignancy unless curatively treated with no evidence of disease for >= 5 years except: adequately treated non-melanoma skin cancer or curatively treated in situ cancer of the cervix
Known brain metastases, unless these metastases have been treated and stabilized
Peptide receptor radionuclide therapy at any time prior to study enrollment
Known hypersensitivity to somatostatin analogues or any component of the 68Ga- DOTATATE or 177Lu- DOTATATE formulations
Patients with uncontrolled infection will not be enrolled until infection is treated per provider discretion
Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2x ULN
Any patient receiving treatment with short-acting somatostatin analogs, which cannot be interrupted for both 24 hours before and after the administration of 177Lu, or any patient receiving treatment with long-acting release somatostatin analogs that cannot be interrupted for at least 4 weeks before the administration of 177Lu- DOTATATE
Any surgery or radiofrequency ablation within 12 weeks prior to enrollment in the study; or prior radioembolization; chemoembolization; or external beam radiation therapy (EBRT) to > 25% of bone marrow, at any time
Any chemotherapy or targeted therapy within 4 weeks prior to enrollment in the study
Current spontaneous urinary incontinence making impossible the safe administration of the radioactive study agent
Any psychiatric illness that prevents patient from informed consent process
Any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
Participant is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment