Mutation profile differences in younger and older patients with advanced breast cancer using circulating tumor DNA (ctDNA).

Abstract

1089 Background: Although the noninvasive nature of ctDNA testing is attractive in an older adult population, less is known regarding the mutation profiles of ctDNA in the older adult breast cancer population as this population is often excluded from studies. Previous tissue testing has shown differences in mutation profiles between older and younger adults with breast cancer. The objective of this study is to assess differences in mutation profiles in the older and younger adult breast cancer population using a ctDNA assay. Methods: Patients (pts) with advanced breast cancer underwent molecular profiling using a plasma-based ctDNA NGS assay (Guardant360) between 5/2015-10/2019 at Siteman Cancer Center. Clinicopathological histories were obtained from the medical record. The results of a multicenter database of pts with advanced breast cancer who had undergone molecular profiling using Guardant360 were obtained. Associations between mutations and age were measured using a Fisher’s exact test. Results: In the single institution cohort, of the 214 patients who underwent testing, 148 (69.16%) were < 65 and 66 (30.84%) ≥ 65 years-old. The most frequently mutated genes in age < 65 pts were TP53 (48.65%), PIK3CA (35.81%), and ESR1 (30.41%) while the most frequently mutated genes in age≥65 pts were PIK3CA (56.06%), TP53 (51.52%), ESR1 (25.76%), and ATM (21.21%). ATM, BRAF and PIK3CA mutations were found more frequently in age≥ 65 pts with ER+ HER2- breast tumors (p < 0.01). MYC and ESR1 mutations were not significantly associated with age, overall or within subtype. Overall ctDNA resulted in change in management in 19.8% pts (40/202). In the larger multicenter cohort, of the 8803 pts who underwent testing, 5367 (61.0%) were < 65 and 3417 (38.8%) ≥ 65 years-old. ATM, ESR1 and PIK3CA mutations were more common in age≥65 pts (p < 0.0001) and MYC mutations were less common in age≥65 pts (p < 0.0001). Conclusions: This study found that ctDNA is a feasible, attractive alternative to traditional biopsies and may identify actionable mutations in older adults with breast cancer. When controlling for subtype, results from a single institution were similar to the larger multicenter cohort showing ATM and PIK3CA were more common in the older adult population. This data suggests there may be additional molecular differences between breast cancer in older compared to younger adults that warrants further investigation.