Background: Invasive lobular breast cancer (ILC) is the second most common histologic subtype of breast cancer following invasive ductal cancer (IDC). ILC accounts for ~10-15% of all breast cancers (~26-40,000 cases annually in the US) and ranks as the 6th most common cancer in women in the US. While there is increasing recognition that ILC has distinct clinical, histologic, molecular, and biological characteristics compared to IDC, it remains understudied. There are very few large cohort analyses comparing clinic-pathological features of ILC, and therefore we performed a large multi-institutional retrospective cohort study. Methods: Investigators from UPMC Hillman Cancer Center, James Cancer Hospital/OSU, and Cleveland Clinic Taussig Cancer Institute/CWRU formed the Great Lakes Breast Cancer consortium, and worked with their respective cancer registries to collect comprehensive data on patients with IDC and ILC seen at their institutions between 1990 and 2017. Descriptive statistics were performed to compare clinic-pathological features, treatments, metastases sites, and co-morbidities. Survival rates were analyzed using the Kaplan-Meier (KM) method and compared using the Cox proportional hazards model. A total of N=38,175 records (N=15,792 for UPMC, N=13,040 for CCF, and N=9,343 for OSU) were included in the study. Results Among the N=38,175 records, we identified N=30,100 unique IDC (not otherwise specific, NOS) (89.3%) and N=3,618 unique ILC cases (10.7%). There were no significant differences between IDC and ILC with respect to laterality of the cancer (IDC: Left 51%, Right 49%; 0.2% Other vs ILC: Left 51%, Right 48%, Other 0.5%) and body mass index (IDC: 28.4 vs ILC: 28.2). In contrast, we observed significant difference with respect to age - patients with ILC were significantly older (61.2 vs 57.5 years; p Conclusions: In the largest cohort of patients with ILC made possible by multi-center collaborations we show that lobular histology carries distinct prognostic implications and that outcomes are significantly worse. This highlights the need for more ILC research and clinical trials for patients with ILC. Citation Format: Steffi Oesterreich, Azadeh Nasrazadani, Jian Zou, Tiffany Onger, Matthew Wright, George Tseng, Bhuvana Ramaswamy, Adrian V Lee, Nicole Williams, Megan Kruse. Comprehensive comparative analysis of invasive ductal and lobular breast cancer cases in great lakes breast cancer consortium [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-02.