Change in management based on actionable mutations in metastatic breast cancer in an ethnically diverse cohort: Single institution experience.
Authors: Premji Sarah , Hoyos Valentina , Bulsara Shaun , Hilsenbeck Susan G. , Nemati Shafaee Maryam , Ellis Matthew James , Osborne C. Kent , Rimawi Mothaffar F. , Nangia Julie R. 
Published: June 2021

e13067 Background: Recently, next generation sequencing (NGS) has been used with increasing frequency to guide therapy decisions for patients with metastatic solid tumors. NGS is a DNA sequencing technology that detects somatically acquired mutations. If an actionable mutation is identified, it may affect prognosis and guide therapy. At our institution we serve a large proportion of minority and underserved patients and analyzed their NGS results to determine if there was a change in management. Methods: Patients with metastatic breast cancer treated at one of two sites at Baylor College of Medicine who underwent NGS via Tempus between 2018-2020 were included. Tempus provided access to the variant database for these patients. We analyzed the charts of 43 patients who underwent NGS via Tempus on tissue, blood or both. In those patients with clinically actionable mutations, we noted if there was a change in management. Utilizing Redcap, we extracted demographics, sites of metastasis, biomarker activity and site, genomic sequencing, and duration and sequencing of therapies given along with clinical trial information. Results: Of the 43 patients included in this analysis, the mean age was 55 years, 33% were African American, 30% were Hispanic, 21% were white/non-Hispanic, 12% were Asian, 4% were other. Two thirds of patients were treated in the Harris Health System (a safety net hospital with a unique and diverse population) while one third was treated at the Baylor St. Luke’s Medical Center (a private academically affiliated institution). Of the 43 patients, 14 had PIK3CA mutations and 3 had a change in management. 2 patients had microsatellite instability (MSI) and received immunotherapy, and 1 patient had a HER2 mutation and entered a clinical trial with Neratinib. Additionally, 2 patients were incidentally found to have MUTYH germline mutation which is associated with polyposis. Conclusions: With increasing frequency, patients with metastatic malignancy undergo NGS in order to determine if there is an actionable mutation that can guide their next line of treatment. However, this technology could be cost prohibitive for many underserved patients. Our study analyzes a unique and diverse population of patients, many of whom are underserved. We were able conduct this testing in our cohort, study the frequency of somatic mutations and monitor for change in treatment. Of the variants analyzed, PIK3CA mutations are actionable and patients can receive Alpelisib + Fulvestrant- however many did not. There was not a large shift in management based on the incorporation of this DNA sequencing technology which suggests that, unlike the case of other solid tumors, there aren’t yet as many actionable targets for patients with metastatic breast cancer. Shared decision making along with consideration of cost is paramount for these patients as we shift into an era of highly personalized medicine.