TNBC and HGSOC PDX models and in vivo treatment

TNBC and Ovarian cancer PDX models establishment was as described (36, 37). PDX models used are described in Table 1 . The study was reviewed and approved by the ethics committees for animal experimentations of the University of Montpellier (CEEA-LR-12028). PDX models were established from fresh tumor fragments obtained from the Pathology Department at the Comprehensive Cancer Center of Montpellier (ICM) after informed consent of the patients. Establishment of PDX models was reviewed and approved by the institutional review board. Approximately 50 mm³ PDX fragments were grafted subcutaneously into the flank of 3-4week old Swiss-nude female mice (Charles Rivers, Saint-Germain-sur-l’Arbresle, France). The present study comprised three experimental arms; vehicle, olaparib and Carboplatin (CBP) treatment comprising 6 to 8 mice per arm. When median tumor volume reached 100-150mm³, mice were randomly distributed in the two arms and treatment was started. Olaparib (Lynparza, AstraZeneca) was administered orally 5 times/week for 5 weeks at 100 mg/kg. CBP (Accord Healthcare, Middlesex, UK) was administered by intra-peritoneal (IP) injection twice per week for 4 weeks at 50 mg/kg CBP. At treatment end, mice were euthanized to collect tumor samples for further biochemical (RNA and proteins) or histological analyses. Some mice were kept for tumor volume monitoring.

Principal bio-clinical characteristics of the patient tumors from which the PDX models were derived.

WT, wild type; Me/Me both alleles methylated. U/Me hemi methylation. TNBC, triple negative breast cancer; HGSOC, High grade serous ovarian carcinoma. NC, not communicated; NA, not applicable; NACT, neoadjuvant chemotherapy; FEC, Fluorouracy. Epirubicin. Cyclophosphamide; RFS, recurrence free survival; OS, Overall Survival.