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

Conditions: Locally Recurrent/Metastatic Triple Negative Breast Cancer

Summary: the study is being done to find out if the results of a pre-treatment biopsy can predict response to cisplatin and radiation treatment for patients with metastatic or recurrent triple negative breast cancer.


Eligibility criteria:
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.

Keywords: treated with concurrent cisplatin treated with radiation therapy homologous recombination repair status biomarker of response 15-032 patients