Next-Generation Sequencing-Directed Therapy in Patients with Metastatic Breast Cancer in Routine Clinical Practice

Abstract

Next-generation sequencing (NGS) followed by matched therapy has opened up new therapeutic options to patients with metastatic breast cancer (mBC). Here we report our experience with this approach in everyday clinical practice. This retrospective study included 95 patients with mBC who were genotyped with the FoundationOne® (CDx) assay in a commercial molecular pathology laboratory. Genetic alterations were identified in all tumor specimens, and 83 patients (87.4%) had a median of 2 (range, 1–6) potentially actionable alterations. A multidisciplinary tumor board recommended genomically guided therapy to 63 patients, 30 of whom received such treatment. Everolimus (n = 15) and anti-human epidermal growth factor receptor 2 (HER2) therapy (n = 6) were most frequently administered. The ratio of progression-free survival (PFS) under NGS-based therapy to PFS under the last line of standard therapy prior to NGS was >1.3 in 13 (43.3%) patients, indicative of a clinical benefit to NGS-directed therapy. One-year overall survival rates were 22.7% (95% CI, 6.5–44.4) in 65 patients allocated to the standard therapy versus 62.9% (95% CI, 41.6–78.2) in 30 patients receiving the matched therapy. In conclusion, NGS-matched treatment improved the clinical outcomes in a subgroup of mBC patients.

Molecular profiling of metastatic breast cancer and target-based therapeutic matching in an Asian tertiary phase I oncology unit

“…In this retrospective study of a cohort of MBC patients from a tertiary oncology centre in Asia, we report a higher PFS for patients receiving matched versus unmatched treatment, a finding consistent with prior publications ( 19 , 24 , 25 ). Median PFS in the current study was 21.0 weeks in pooled treatment event analysis, a value that is difficult to compare across publications of early-phase trial cohorts due to the heterogeneous nature of such populations.…”

Role of the Molecular Tumor Board for the Personalized Treatment of Patients with Metastatic Breast Cancer: A Focus on the State of the Art in Italy

“…The one-year overall survival rates were 22.7% in the 65 patients assigned to standard therapy compared with 62.9% in the 30 patients who received combination therapy. Thus, treatment combined with NGS improved clinical outcomes in a subset of patients with MBC [ 37 ].…”

The Diversity of Liquid Biopsies and Their Potential in Breast Cancer Management

“…Targeted therapy matched to the genomic alterations improved the PFS only in case the variants were ESCAT LOE I or II [212]. The definition of actionable variants by other means resulted in reports of 44-95% of patients having at least one actionable variant for therapy guidance [213][214][215][216][217][218][219]. Only in 40/104 patients with actionable alteration, clinical management was changed [219].…”

“…Only in 40/104 patients with actionable alteration, clinical management was changed [219]. The 1-year OS rate was 65.9% in women treated based on their genomic alteration versus 22.7% in patients who received standard chemotherapy [218].…”