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.