Impact of multimodal, multidisciplinary care on clinical outcomes in patients with breast cancer and leptomeningeal carcinomatosis.

e13043 Background: Leptomeningeal carcinomatosis (LMC) is a rare consequence of metastatic breast cancer (MBC) with a dismal prognosis, with a historical 15-week median overall survival (OS). There is no standard of care treatment (tx), and a paucity of data on MBC subtype specific incidence and prognosis. The impact of newer CNS penetrating systemic (sys) tx like antibody drug conjugates (ADCs) and multimodal CNS tx on BC related LMC prognosis is underreported in contemporary literature. Here, we present a real-world analysis of a contemporary cohort of patients (pts) with LMC. Methods: This is a single-institution retrospective study of 48 pts diagnosed with BC related LMC between 2016-2024, based on radiographic features and/or positive cerebrospinal fluid (CSF) cytology or CSF circulating tumor cells (CTC). Pts consented to share information with a research biorepository (IRB 181755). We conducted a retrospective chart review of clinical features, tx, and OS. Results: 25 pts (52%) had invasive ductal carcinoma, 14 (29%) had invasive lobular carcinoma, 4 (8%) had metaplastic carcinoma, 2 (4%) had inflammatory carcinoma, and 3 (6%) had mixed histology. 20 pts (42%) had estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) BC, 4 (8%) had HER2+ BC, and 24 (50%) had triple negative BC (TNBC). Median age at LMC diagnosis (dx) was 50 years. Median time from MBC to LMC dx varied significantly by subtype: 24.5 months (mos) in ER+/HER2-, 7 mos in HER2+, and 4.5 mos in TNBC (p = 0.01). Prior tx with ADCs (n = 25) was associated with a significantly longer time from MBC to LMC dx (21 vs. 8 mos, p = 0.037). 32 pts (67%) had confirmed LMC by CSF cytology or CTC. 28 pts (58%) received intrathecal chemotherapy (ITC), 9 (19%) received craniospinal irradiation (CSI), 26 (54%) received whole brain radiation (WBRT), and 18 (38%) received ITC+ RT (CSI or WBRT). Median OS varied by subtype: 7.0 mos for ER+/HER2-, 22.4 mos for HER2+, and 5.8 mos for TNBC. Significantly longer OS was seen with ITC+/- RT vs RT alone (9.1 vs. 1.3 mos, p < 0.0001). 20 pts received ADCs post LMC dx, all of whom also had CNS tx (ITC and/or RT), with a significantly longer OS than pts with CNS tx and no ADC (13 vs. 5 mos, p = 0.002). Eastern Cooperative Group performance status (median = 1) did not vary by ADC use. In pts naïve to ADCs pre-LMC dx, a longer OS trend was seen with ADC tx post LMC dx vs other sys tx (32 vs 7 mos, p = 0.14). In pts with LMC and HER2 low or ultralow MBC (n = 25) who received CNS tx, the addition of trastuzumab deruxtecan (n = 6) significantly improved OS (23 vs 5.5 mos, p = 0.02) compared to CNS tx +/- other sys tx. Conclusions: LMC in BC historically has a grim prognosis. Our institutional experience supports that a multimodal, multidisciplinary approach with sys tx and CNS tx improved OS in LMC in BC. Moreover, ADCs, when added to CNS tx, significantly improved OS. Larger prospective studies are needed to inform tx paradigms.