Abstract 80: Glucocorticoids mediate DCIS transition to IDC through myoepithelial cell apoptosis

The most accepted theory in breast cancer evolution is the linear progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). DCIS is defined by a clonal proliferation of epithelial cells that accumulate within the lumen of a duct and surrounded by the myoepithelial cells layer and the basement membrane. The challenge is to predict which of the DCIS lesions will eventually progress to IDC and which will remain stable for a long time. Understanding the progression from DCIS to IDC is crucial to properly treat DCIS patients and to develop new and more approachable therapeutic strategies in this stage. The microenvironment, as well as stress factors like glucocorticoids, exerts strong influences in DCIS to IDC transition. These factors have been previously implicated in breast cancer progression however its role in the first stages of breast cancer and particularly in myoepithelial cells regulation remains elusive. In order to clarify glucocorticoids role in this breast cancer stage, we evaluated the effects of corticosterone and cortisol in epithelial cells and myoepithelial cells using in vitro 2D and 3D and in vivo techniques. Glucocorticoids induced a decreased in laminin levels and favour the disruption of the myoepithelial cell layer through myoepithelial cells apoptosis promotion. In addition, increased corticosterone levels, in an in vivo stress murine model, fostered the transition from DCIS to IDC via myoepithelial cell apoptosis and basement membrane vanishing. Furthermore, myoepithelial cell apoptosis is a more frequent event in DCIS+IDC than in DCIS breast cancer patients. Our findings show that stress, through glucocorticoids, plays a role in the progression of DCIS to IDC, and particularly by promoting apoptosis of myoepithelial cells and the apoptosis in myoepithelial cells seems to be a requirement to achieve invasive features in breast cancer patients. Citation Format: Arantzazu Zubeldia-Plazaola, Leire Recalde-Percaz, Nuria Moragas, Mario Mancino, Aleix Noguera, Miquel Prats de Puig, Flavia Guzman, Pedro Gascon, Paloma Bragado, Gemma Fuster. Glucocorticoids mediate DCIS transition to IDC through myoepithelial cell apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 80.