The Effect of Germline Pathogenic Variants in the Upgrade Rate to Breast Cancer Among Patients Diagnosed With Atypical Lobular Hyperplasia and Lobular Carcinoma In Situ on Core Needle Biopsy

INTRODUCTION: Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) are high-risk lesions that may be identified on biopsy performed for evaluation of radiologic abnormalities. Most women diagnosed with ALH and LCIS do not develop breast cancer. Treatment recommendations are ill-defined when these lesions are discovered in patients with germline pathogenic variants (PV) in breast cancer predisposition genes. PATIENTS AND METHODS: We reviewed our institutional databases and identified patients diagnosed on core needle biopsy (CNB) after screening mammography with lobular neoplasia (LN), including ALH and LCIS as their most significant pathology, and queried the electronic health record to identify those who had germline testing. RESULTS: In our cohort, among 70 patients who had informative genetic testing, where the majority of patients had a strong personal and family history of cancer, the prevalence of high- and moderate-penetrance germline PV carriers was 24.5%. Excision was performed in 40% of the patients with PV (n = 28). An upgrade to breast cancer was identified in 28.5%. All patients with an upgrade to cancer had both a PV and a family history of breast cancer. Sixteen patients (17.2%) with LN and negative genetic testing underwent excision, and there were no upgrades to cancer (P = .04). CONCLUSION: Patients with LCIS on core biopsy and known PVs demonstrated significant upgrade rates, supporting consideration of excision at the time of diagnosis. Knowledge of germline PV status along with clinical, pathologic and radiologic findings can potentially be used to de-escalate surgical therapy in individuals without germline PVs.