Key uncertainties include: the molecular basis of multifocality (clonality, drivers such as E-cadherin loss in lobular carcinoma), understudied psychosocial impact and patient-reported outcomes (anxiety, preference for mastectomy despite BCT eligibility), and limited outcomes data in the genomic-assay era (e.g., whether low-risk signatures truly neutralize MF/MC risk). The gene discussed is CDH1; the disease is Anxiety.