ESPE Abstracts

Benign breast diseases (BBD) have always been neglected in comparison to cancer, despite the fact that there are many more patients with such diseases than patients presenting to a breast clinic for cancer, especially in young women. So far, BBD have been the subject of a relatively few isolated and unconnected studies, and earlier related work has often been ignored. This situation has led to a great deal of confusion, especially because different authors have their own nomenclature for benign lesions of the breast, and, unfortunately, a unique and unequivocal definition has not yet been commonly accepted. Hence, it is even more difficult to find in the literature data concerning the mechanisms involved in the development of such disorders, especially when it concerns rare BBD or in adolescents. Breast tissues are under a complex system of control by systemic factors, particularly hormones acting through their respective receptors, as well as a number of local factors. This network starts with the onset of puberty. This includes paracrine hormones, released by one type of cell to influence adjacent cells of similar or differing function; juxtacrine factors, situated on the surface of the producing cell to influence adjacent cells by direct contact; and autocrine hormones, which act on the same cell by intracellular or surface receptors. All of these hormones interact, as is true for systemic hormones, by influencing locally derived factors— cell adhesion-related proteins as well as autocrine and paracrine hormones—to produce signal pathways that finally result in cell regulation and stimulation. We recently identified in a population of women, including adolescents, with multiple breast fibroadenomas (MFA), a germline heterozygous variant in exon 6 of the human Prolactin Receptor gene (hPRLR), encoding Ile146 to Leu (I146L) substitution in the extracellular domain of the receptor. This sole substitution was sufficient to confer constitutive activity to the receptor variant, as reflected by PRL-independent activation of the PRLR/Stat5 cascade and proliferative and antiapoptotic effects in various cell lines. However, in a more recent study, we suggested that these PRLR_I146L and PRLR_I176V variants are not associated with breast cancer or MFA risk. However, one cannot exclude that low but sustained PRLR signaling may facilitate or contribute to pathological development driven by oncogenic pathways. The role of such variants in developing benign breast tumors will be discussed, especially in adolescents. Others benign breast diseases, in adolescents will be discussed in terms of diagnosis, management and therapeutic approaches.