Germline Cancer Predisposition Gene Mutations and Upgrade Rate to Breast Cancer Among Patients with Pleomorphic and Florid Lobular Carcinoma in Situ.

BACKGROUND: Pleomorphic lobular carcinoma in situ (PLCIS) and florid lobular carcinoma in situ (FLCIS) are uncommon entities with variable rates of upgrades. Germline pathogenic variant cancer predisposition genes (PVs) are associated with increased breast cancer risk and influences management recommendations. DESIGN: Patients diagnosed with PLCIS and FLCIS over a 24-year period were identified. Clinical, radiologic, pathologic, treatment, and genetic testing was extracted from the electronic health record. The immediate rate of upgrade to invasive breast cancer and subsequent recurrence rates were calculated. RESULTS: Forty-six patients with PLCIS and FLCIS as the most significant lesion on biopsy were identified. Of those with genetic testing, the majority had no germline PV (82.6%). Of those with PV, germline mutations in CHEK2 (4.3%), CDH1 (2.2%), BRCA2(2.2%), and VHL (2.2%) were identified. Forty-six patients underwent surgery to include wide local excision in (84.7%) and mastectomy in (15.2%). Twenty-four percent of patients with PLCIS (n=11) had an upgrade to invasive carcinoma on excision, of which five had PV (36%). Upgrades to cancer were more common in patients with PV (p=0.0198). Six patients (13%), developed ipsilateral breast cancer recurrences, of which 3 (50%) had known PV with a median time to recurrence of 83.8 months. CONCLUSION: In patients with PLCIS and PV, the presence of PV may represent an additive risk factor for the presence of invasive carcinoma on excision and ipsilateral breast cancer recurrence. Knowledge of the oncogenic drivers of tumors in these patients may help to improve risk assessment, surveillance and treatment recommendations.