Breast cancer organoids from a patient with giant papillary carcinoma as a high-fidelity model

Abstract

Background: Papillary carcinoma is an uncommon type of breast cancer. Additionally, patients with huge breast papillary carcinoma are extremely rare in clinical practice. To improve therapeutic effect on such patients, it is urgent to explore biologically and clinically relevant models of the disease to discover effective drugs. Methods: We collected surgical tumor specimens from a 63-year-old Chinese woman who has been diagnosed breast papillary carcinoma. The tumor was more than 15 cm in diameter, and applied to establish patient-derived papillary carcinoma organoids that could continuously propagate for more than 6 months. Results: The papillary carcinoma organoids matched the histological characteristics of orginal tumor by H&E staining identification, and maintained the expression of the breast cancer biomarkers by IHC, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2) and antigen Ki-67 (Ki67). In addition, we performed a 3-D drug screening to examine the effects of endocrine drugs (Fulvestrant, Tamoxifen) and targeted therapy drugs (Palbociclib, Everolimus, BKM120) on breast papillary carcinoma in the mimic in vivo environment. The drug sensitivities of our breast papillary carcinoma organoids were investigated as follows, Fulvestrant (IC50 0.275 μmol), Palbociclib (IC50 2.21 μmol), BKM120 (IC50 3.81 μmol), Everolimus (IC50 4.45 μmol), Tamoxifen (IC50 19.13 μmol). Conclusions: These results showed that an effective organoid platform for 3-D in vitro culture of breast cancer organoids from patients with breast papillary carcinoma could be used to identify possible treatments, and might be commonly applied to explore clinicopathological characteristics of breast papillary carcinoma.