Patient derived xenograft models of hormone receptor positive and HER2 negative breast cancer from Indian patients

Limited success has been achieved in the development of patient-derived xenografts (PDX) models of hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2-negative (HER2-negative) metastatic breast cancers that are resistant to hormone therapy (HT). We aimed to establish and characterize PDX models from HR+/HER2-negative breast cancer. A total of 28 tumors were orthotopically implanted in the fourth mammary fat pad of female NOD-SCID mice. Seven PDXs were developed, five from heavily pretreated HT-resistant patients and two from treatment-naïve patients. Three of the seven PDXs (two from HT-resistant and one from treatment-naive) converted into lymphoma by generation 2 (G1). The median time for developing palpable G0 PDX was 100 (45-150) days for five HT-resistant tumors, and the mean time was 178 (160-196) days for two treatment-naïve tumors. Successful PDXs were developed from three HT-resistant tumors (two up to G4, one up to G0), including one of solid papillary morphology, and one treatment-naïve tumor (up to G2). Histopathological analyses showed complete concordance for all 14 PDX generations (11 resistant, 3 treatment-naïve) with their corresponding patient's tumor for estrogen receptor (ER), progesterone receptor (PR) and HER2. Short tandem repeat (STR) profiling using 18 markers was done in 8/11 HT-resistant generations and 3/3 treatment-naïve generations and showed good concordance of 51-100% and 91-100%, respectively, with patient tumors. We successfully established PDXs of HT-resistant and treatment-naïve HR+/HER2-negative breast cancer, which will be valuable tools for understanding molecular resistance mechanisms and for exploring novel treatment strategies.