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Background: Invasive lobular carcinoma (ILC) exhibits differences in molecular and biological characteristics compared with invasive ductal carcinoma (IDC). We aim to compare breast cancer-specific survival (BCSS) between patients with ILC and IDC., Methods: We used data from the Surveillance, Epidemiology, and End Results database (1992-2020). Logistic regression analyses were conducted to identify factors associated with treatment modalities. We examined BCSS at different time points using a cox regression model with time-dependent coefficient., Results: A total of 343,397 patients with IDC and 39,859 patients with ILC were included. Patients with ILC had more advanced-stage disease (stage II, 35% vs. 34%; stage III, 16% vs. 11%) and a higher rate of hormone receptor-positive disease (97% vs. 81%). Compared with patients with IDC, patients with ILC had better BCSS in the first five years (HR = 0.71; P < 0.001) but worse BCSS in later years (HR = 1.30, P < 0.001 in years 6-10; HR = 1.75, P < 0.001 in years 11-15; and HR = 2.17, P < 0.001 in years 16-20)., Conclusions: Patients with ILC survive better in early years but worse in later years compared with patients with IDC. Future studies are required to identify patients with ILC who are at risk of late recurrence or mortality., Impact: The results of this study add to the currently conflicting literature of survival of ILC and demonstrate the importance of evaluating novel therapeutic approaches and extended therapy for patients with ILC., (©2024 American Association for Cancer Research.)

Purpose: Breast cancer cells disseminate to distant sites via Tumor Microenvironment of Metastasis (TMEM) doorways. The TIE2 inhibitor rebastinib blocks TMEM doorway function in the PyMT mouse model of breast cancer. We aimed to assess the safety and pharmacodynamics of rebastinib plus paclitaxel or eribulin in patients with HER2-negative metastatic breast cancer (MBC)., Patients and Methods: This phase Ib trial enrolled 27 patients with MBC who received 50 mg or 100 mg of rebastinib PO BID in combination with weekly paclitaxel 80 mg/m2 (if ≤ 2 prior non-taxane regimens) or eribulin 1.4 mg/m2 on days 1 & 8 (if ≥ 1 prior regimen). Safety, tolerability and pharmacodynamic parameters indicating TIE2 kinase inhibition and TMEM doorway function were evaluated., Results: No dose-limiting toxicities in cycle 1 or 2 were observed among the first 12 patients at either rebastinib dose level. The most common treatment-emergent adverse events (AEs) were anemia (85%), fatigue (78%), anorexia (67%), leukopenia (67%), increased alanine aminotransferase (59%), hyperglycemia (56%), nausea (52%), and neutropenia (52%). AEs attributed to rebastinib include muscular weakness and myalgias. Intraocular pressure increased at the 100 mg rebastinib dose level, whereas angiopoietin-2 levels increased at both dose levels, providing pharmacodynamic evidence for TIE2 blockade. Circulating tumor cells decreased significantly with the combined treatment. Objective response occurred in 5/23 (22%) evaluable patients., Conclusions: In patients with MBC, the recommended phase 2 dose of rebastinib associated with pharmacodynamic evidence of TIE2 inhibition is either 50 or 100 mg PO BID in combination with paclitaxel or eribulin.