Twana Alkasalias

Abstract Women with germline BRCA1 pathogenic variants face a very high risk of early-onset triple-negative breast cancer (TNBC), with risk-reducing mastectomy currently the only established preventive option. Emerging evidence suggests aberrant progesterone signalling contributes to TNBC risk, while preclinical studies indicate progesterone receptor modulators such as mifepristone may substantially reduce cancer development.

Abstract Progesterone receptor antagonists such as mifepristone have emerged as candidates for breast cancer prevention, particularly in high-risk populations such as BRCA1/2 pathogenic variant carriers. However, their impact on endometrial safety remains insufficiently characterized, raising concerns about unopposed oestrogen stimulation in the setting of impaired DNA repair.

Abstract In order to advance personalized primary cancer prevention, surrogate endpoint biomarkers in distant, easy to access tissues (i.e., field defect indicators) reflecting field cancerization in the organ at risk are essential. Here we utilized medroxyprogesterone acetate and 7,12-dimethylbenzanthracene to induce mammary gland cancers in mice.