Homologous Recombination Repair Status as a Biomarker of Response in Locally Recurrent/Metastatic Triple Negative Breast Cancer Patients Treated With Concurrent Cisplatin and Radiation Therapy

Inclusion Criteria:

Histologically-confirmed invasive triple negative breast cancer (ER <1%, PR <1%, her-2-neu 0-1+ by IHC or FISH-negative) or as determined by MD discretion
Radiation to the recurrent or metastatic site is clinically indicated and would be considered standard care for palliation or for locoregional control
Age ≥18 years
Tumor to be irradiated is measurable by RECIST 1.1 or PRC
Willingness to undergo tumor biopsy prior to initiation of treatment
Life expectancy greater than 6 months
ECOG performance status 0-2
Any prior chemotherapy is allowed including prior treatment with platinum-containing chemotherapy
Prior treatment with FDA-approved or investigational biologics or novel molecularly target therapies, including oral or IV formulations, are permitted.
Patients must be off prior targeted therapy for at least 14 days prior to study biopsy.
Use of an effective means of contraception in women of child-bearing potential
Ability to comprehend and sign informed consent

Adequate organ and marrow function within 14 days prior to study entry, defined as:

Absolute neutrophil count (ANC)>1000/mm3
Hemoglobin >9 gm/dl
Platelets >100,000/mm3
Serum creatinine <1.5 mg/dl OR creatinine clearance of ≥ 50 cc/min
SGOT/SGPT<2.5X institutional ULN (<5X ULN if known liver metastases)

Exclusion Criteria:

Unmeasurable target tumor site by RECIST 1.1 or PRC (ex: lesions <2 cm on CT or MR scan, leptomeningeal disease, ascites, pleural/pericardial effusion, lymphangitis, non-FDG-avid skin lesions)
Brain metastases requiring focal or whole brain radiation will be excluded, as these lesions cannot be biopsied and can have life expectancies <6 months.
Inability to obtain a biopsy of the tumor as deemed by the study Interventional Radiologist
Prior chemotherapy completed <7 days prior to planned study entry

Prior RT is allowed and must have been completed more than 7 days before planned study entry.

Note: For re-irradiation cases, standard departmental guidelines should be followed so as to not exceed normal tissue
Life expectancy less than 6 months
Intercurrent illness or other major medical condition or comorbid condition that might affect study participation (uncontrolled renal, pulmonary or hepatic dysfunction or infection)
Renal dysfunction for which cisplatin dose would be considered unsafe.
Women on study must be neither pregnant nor nursing nor expected to become pregnant during therapy. For premenopausal women, negative pregnancy test within 14 days of RT is required.
Concurrent active malignancy other than non-melanomatous skin cancer or carcinoma in-situ of the cervix, unless treatment for the previous cancer was completed >2 years prior to study entry and patient has remained disease-free.