Treatment patterns, genomic characteristics, and outcomes among patients with metastatic lobular breast cancer.

Abstract

1119 Background: Invasive lobular carcinoma (ILC) is characterized by loss of E-cadherin expression and accounts for 10-15% of breast cancer diagnoses. ILC differs from the more common invasive carcinoma of no special type in the pattern of metastatic spread and genomic characteristics; however, clinicopathologic characteristics among patients with metastatic ILC are not well described. Here, we present comprehensive treatment, genomic, and outcome data in a large single-center cohort of patients with metastatic ILC. Methods: Patients were identified for inclusion in this retrospective study if they had ILC histology on early-stage breast biopsy/surgical pathology and/or CDH1 mutation on metastatic site biopsy; all patients were required to have MSK-IMPACT somatic next generation sequencing (NGS) data available. Clinicopathologic characteristics were abstracted from the EMR. The Kaplan-Meier method was used to estimate overall survival (OS). The log-rank test was used to compare OS by ILC subtype and by genetic mutations. Wilcoxon rank sum test and Kruskal-Wallis test were used to compare number of treatment lines by receptor status. Results: 654 patients were included, of whom 99.8% were female, 89% were white, and 96% non-Hispanic. 438 (67%) had recurrent disease whereas 212 (33%) had de novo metastatic disease. Among 307 with ILC histologic subtype data available, 139 (45%) had classic type, 65 (21%) had pleomorphic, 45 (15%) had mixed, and 58 (19%) had other ILC subtypes. 454 (87%) had hormone receptor-positive (HR+) disease, 45 (9.1%) had HER2+ disease, and 50 (9.5%) had triple negative disease at metastatic diagnosis. In the total cohort, median number of treatment lines for metastatic disease was 4 (IQR 2-7) and median number of chemotherapies was 2 (IQR 1-3). In the HR+ cohort, median number of endocrine therapies was 2 (IQR 1-3). Among patients with genomic data from a biopsy obtained within 2 months of metastatic diagnosis, 79% had a CDH1 mutation, 48% had a PIK3CA mutation, 5.6% had an AKT1 mutation, 11% had a PTEN mutation, 9.3% had an ESR1 mutation, 17% had a HER2 mutation, and median tumor mutation burden (TMB) was 4 (IQR 3-7); 17% had TMB ³10. Median OS in the total cohort was 4.4 years (95%CI 4.1-4.8). OS did not differ significantly by ILC subtype ( p = 0.8). OS differed significantly by CDH1 mutation status (wt 5.3 years, 95%CI 4.1-6.6; mut 3.7 years, 95%CI 3.5-4.2, p = 0.01), PIK3CA status (wt 4.6 years, 95%CI 4.0-5.8; mut 3.4 years, 95%CI 3.1-3.9, p < 0.001), and PTEN status (wt 4.2 years, 95%CI 3.7-4.5; mut 3.4 years, 95%CI 2.2-4.3, p = 0.008). OS did not differ significantly by HER2 , AKT1 , or ESR1 mutation status. Conclusions: In a large single-center cohort of patients with metastatic ILC, OS did not vary by ILC subtype, but did differ significantly by CDH1, PIK3CA, and PTEN mutation status. This underscores the prognostic importance of NGS in metastatic ILC.