Next Generation Sequencing (NGS): a possible game changer in metastatic breast cancer

Background: NGS has been introduced into the clinics with the aim of sequencing long and complex genes for tumor sample, in order to identify driver and/or targetable alterations. Several companies and academic centers have implemented NGS assays to guide treatment decisions, even though there are no clear recommendations from scientific societies about their use in daily clinical practice. Patients and methods: Since 2019 NGS analysis was performed in 32 MBC patients’ tissues at Modena Cancer Center, as for clinical judgement during the course of MBC. Oncomine™ was mainly used for the assay. The aim was to define the PI3K mutational status, since Alpelisib - an a-subunit selective PI3K inhibitor - had shown to improve PFS in PI3K mutated HR+/HER2- MBC patients in SOLAR-1 and BYLIEVE trials. Results: Twenty (62%) NGS analysis were performed on MBC samples, the other (13) on primary breast cancer. Table1 summarize the clinical-pathological characteristics of patients. At least 1 mutation was found in 25 (78%) samples. A PI3K mutation was detected in 14 (44%) cases, with E542K as the most frequent. In 10 out of 14 cases, PI3K mutation was associated with other gene mutations. FGFR3, FGFR4 mutations and FGFR2 amplification were described in 4, 2 and one patients respectively. Two patients showed AKT1 mutation, in one case was associated with PTEN mutation. Two of the patients with PI3K mutation were treated with Alpelisib + Fulvestrant. The patient with FGFR1 amplification was eligible for a phase II clinical trial. Conclusions: NGS performed in this cohort of MBC patients allowed therapeutic decisions in about 10% of cases. Although PI3K mutational status for eligibility to Alpelisib can be cheaply studied by RT-PCR, NGS assay can provide wider information about other gene mutations, useful for patients’ selection for clinical trials. In the era of precision medicine, knowing the mutational status of MBC early in patient history can change the therapeutic algorithm.