Gain-of-function Prolactin Receptor Variants Are Not Associated With Breast Cancer and Multiple Fibroadenoma Risk

Context: In a cohort of 95 women with multiple breast fibroadenomas (MFAs), we recently identified patients harboring germline heterozygous variants of the prolactin receptor (PRLR) exhibiting constitutive activity (PRLRI146L and PRLRI176V). Objective: This study sought to better delineate the potential role of PRLR gain-of-function variants in benign and malignant mammary tumorigenesis. Design: This was an observational study and transgenic mouse model analysis. Setting: The study took place at the Department of Endocrinology, Reproductive Disorders and Rare Gynecologic Diseases, Pitie Salpetriere, Paris, and Inserm Unit 1151, Paris. Patients or Other Participants: We generated a second MFA cohort (n = 71) as well as a group of control subjects (n = 496) and a cohort of women with breast cancer (n = 119). We also generated two transgenic mouse models carrying the coding sequences of human PRLRI146L or PRLRWT. Intervention: We aimed to determine the prevalence of PRLR variants in these three populations a...