Abstract P1-02-08: Comparison of clinical features and outcomes for pleomorphic invasive lobular carcinoma vs. non-pleomorphic invasive lobular carcinoma
Authors: Wright Matthew D. , Dempster Marcus S. , ElSherif Ayat , Cocco Daniela , Valente Stephanie A. , Li Hong , Kruse Megan L. 
Published: March 2022

Abstract
Background: Invasive lobular carcinoma (ILC) is the second most common invasive breast cancer histology. Within ILC histology, there are multiple subtypes. The most common subtype is “classic” characterized by small single files of cells invading the stroma. Another subtype of clinical interest is “pleomorphic” which is characterized by larger cells with varied nuclear appearance. Rare and not well understood, pleomorphic ILC is traditionally viewed as an aggressive form of ILC. Studies have shown a relatively consistent association between pleomorphic ILC and certain high risk features such as advanced stage, HER2 positivity, and lymph node involvement. Survival outcome data comparing pleomorphic ILC to non-pleomorphic ILC has yielded varied results. Methods: A retrospective study of a large institutional database was conducted to characterize patients with ILC treated from 2004-2017. Patient and disease characteristics were recorded, including disease staging, biomarker profile, specific ILC histology, treatment details, and recurrence events. Findings were analyzed and overall survival (OS) and recurrence free survival (RFS) were compared between pleomorphic and non-pleomorphic ILC cohorts. Propensity score matching was also completed to account for confounding variables. Results: A total of 691 patients who had surgery were studied (mean age 61.6 ± 11.6 years old, 86.9% Caucasian, 98.3% with endocrine therapy), including 100 (14.4%) with pleomorphic ILC and 591 (85.5%) with non-pleomorphic ILC. Compared to non-pleomorphic ILC, pleomorphic ILC was less likely to be estrogen receptor (ER) positive (94% vs. 98%, p=0.004), more likely to be HER2 positive (12% vs. 7%, p=0.07), more likely to be grade 3 (33% vs. 2%, p&lt;0.001), less likely to be diagnosed at a lower T stage (Stage I 38% vs. 58%, Stages II-III 61% vs. 41%, p&lt;0.001), and less likely to be diagnosed with axillary lymph node involvement (node positivity 48.5% vs. 66%, p&lt;0.001). Mastectomy rates were 65% in pleomorphic ILC and 52% in non-pleomorphic ILC (p=0.022). Patients with pleomorphic ILC were more likely to receive chemotherapy (66% vs. 36%, p&lt;0.001). Pleomorphic ILC patients were also more likely to receive HER2-directed therapy (12% vs. 5.8%, p=0.02). Median follow-up was 6 years. There was no significant difference in OS and RFS between cohorts before matching for age, BMI, stage, surgery type, and chemotherapy. Although not statistically significant, pleomorphic ILC appears to have better RFS and OS between propensity score matched 91 pairs (10-year RFS: 79% vs. 71.5%, p=0.27 and 10-year OS: 86% vs. 76%, p=0.13). Exploratory analysis also suggests that multifocal pleomorphic ILC is associated with worse RFS and OS compared to unifocal pleomorphic ILC. Conclusions: Pleomorphic ILC was found to have more advanced disease at presentation in the breast but not in lymph nodes. At our institution, it was treated with more chemotherapy compared to non-pleomorphic ILC, likely related to higher grade, lower ER-positivity, and higher HER2-positivity. After propensity score matching, pleomorphic ILC appears to have better RFS and OS compared to non-pleomorphic ILC. This was particularly noticeable three years after surgery and may reflect more aggressive management. These data reveal some unexpected trends that challenge the notion of pleomorphic ILC having worse outcomes compared with non-pleomorphic ILC. This highlights the need for additional studies to better understand multiple aspects of ILC and its subtypes.
Citation Format: Matthew D. Wright, Marcus S. Dempster, Ayat ElSherif, Daniela Cocco, Stephanie A. Valente, Hong Li, Megan L. Kruse. Comparison of clinical features and outcomes for pleomorphic invasive lobular carcinoma vs. non-pleomorphic invasive lobular carcinoma [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-08.