Clinical Management and Oncological Outcomes of Pure Pleomorphic and Florid Lobular Carcinoma In Situ of the Breast: Final Results from the MultiLCIS/OPBC International Multicenter Study

Background: Pure pleomorphic (PLCIS) and florid (FLCIS) lobular carcinoma in situ are rare and poorly understood breast lesions. Their management is not standardized due to limited evidence. We gathered the first large international multicenter cohort to analyze oncological outcomes and identify optimal treatment. Methods: This multicentric retrospective study (ClinicalTrials.gov-NCT06133465) collected data from 79 centers worldwide. Patients diagnosed with pure PLCIS and/or FLCIS on core biopsy (CB) and/or final specimen pathology were included. Cases with associated IC and/or DCIS were excluded. Pathology review by a dedicated breast pathologist and a minimum follow-up of 2 years were required. Results: Data from 1063 patients treated between 01/2004 and 12/2022 were collected. Among these, 153 showed P/FLCIS only on final histology. Among 910 pure P/F-LCIS cases diagnosed on core-biopsy, 228 (25.1%) cases upgraded to IC, and 78 (8.6%) to DCIS, with a total upgrade rate of 33.6% (306/910). Multivariate analyses identified size (lesions >15mm associated with OR 2.31 (1.6,3.33), p=0.0001) and multifocal/multicentric disease (OR 2.57 (1.81,3.66), p=0.0001) as predictors of upgrade. Upgrade rates were similar in PLCIS (34.6%) and FLCIS (30.7%) (p=0.266). Our analysis focused on the 757 cases confirmed as pure P-/FLCIS on surgical specimen. The median lesion size was 11 mm (IQR, 7-20). Mastectomy was performed in 95 cases (40 bilateral), while 662 underwent lumpectomy. Sentinel node biopsy was performed in 153/757 (20.2%) cases, with no positive nodes identified. After a median follow-up of 75 months (45,116), ipsilateral breast recurrence (IBR) occurred in 82/757 (10.8%) cases, comprising 53 IC, 11 DCIS and 18 P-/FLCIS. Multivariate analysis identified margin status as the strongest predictor of IBR, close margins being associated with OR 3.99 (2.2,7.25), p=0.0001) and involved margins with OR 12.02 (5.72,25.23), p=0.0001). Necrosis (OR 4.54 (2.62,7.88), p=0.0001) and size >15mm (OR 4.19 (2.44,7,19), p=0.0001) were also significantly associated with IBR, while endocrine treatment (ET) was protective (OR 0.25 (0.12,0.51), p=0.0002). Radiotherapy reduced recurrences only in PLCIS cases (OR 0.43 (0.2,0.92), p=0.0289). Conclusions: In this largest cohort reported to date, the 33.6% upgrade rate of pure P/FLCIS to IC or DCIS supports surgical excision as the first recommended therapeutic approach. Axillary surgery should be omitted. Surgery with clear margins should be the mainstay of treatment, and ET may be considered to reduce recurrence rates. Radiotherapy should be reserved to selected high-risk cases.