SafeSEQ Panel

Breast Cancer SafeSEQ

The SafeSEQ Breast Cancer Panel is a clinical grade, ultra-sensitive liquid biopsy solution for the identification of gene mutations in PIK3CA, ESR1, AKT1, ERBB2, TP53, and KRAS to detect established and emerging predictive markers, resistance mutations, and frequently occurring genetic alterations in breast cancer.

This graph shows the prevalent “truncal mutations” for the SafeSEQ Breast Cancer Panel. The SafeSEQ Breast Cancer Panel can detect clinically relevant mutations in circulating tumor DNA (ctDNA) from patients with metastatic breast cancer with sensitivity equivalent to the Sysmex highly clinically validated OncoBEAM liquid biopsy Breast Cancer Panel, which detects gene mutations in PIK3CA, AKT1, and ESR1 with a limit of detection 0.04% mutant allele frequency (MAF).

The SafeSEQ Breast Cancer Panel can detect clinically relevant mutations in circulating tumor DNA (ctDNA) from patients with metastatic breast cancer with sensitivity equivalent to the Sysmex highly clinically validated OncoBEAM liquid biopsy Breast Cancer Panel, which detects gene mutations in PIK3CA, AKT1, and ESR1 with a limit of detection 0.04% mutant allele frequency (MAF). The robust accuracy at low allelic frequencies observed for SafeSEQ in this study demonstrates the advantages of highly focused panels for defined clinical intended uses. (See figure below reference 1)

SafeSEQ sensitivity has 99.2% agreement with OncoBeam™

This chart measures SafeSEQ sensitivity and shows that SafeSEQ has a 0.97%  agreement with OncoBEAMTM for mutant allele frequency (MAF). The SafeSEQ Breast Cancer Panel can detect clinically relevant mutations in circulating tumor DNA (ctDNA) from patients with metastatic breast cancer with sensitivity equivalent to the Sysmex highly clinically validated OncoBEAM liquid biopsy Breast Cancer Panel, which detects gene mutations in PIK3CA, AKT1, and ESR1 with a limit of detection 0.04% mutant allele frequency (MAF). The robust accuracy at low allelic frequencies observed for SafeSEQ in this study demonstrates the advantages of highly focused panels for defined clinical intended uses.

R2 = 0.9709

SafeSEQ Breast Cancer Panel characteristics

The following chart shows SafeSEQ Breast Cancer Panel characteristics and shows regions analyzed, which are 27 regions across clinically relevant oncogenes and tumor suppressors for breast cancer. Mutation types detected are SNV, MNV, and indels. Sample requirements are equal to or less than 2 milliliters of plasma. Turnaround time is equal to or less than 2 weeks. Sequencing platform is Illumina. Data format is mutation calls with frequency data, including MAF, and mutant molecules per volume plasma.

Clinical Relevance

Therapeutic selection:
Enables maximum identification of biomarker-positive patients eligible for therapy. Less sensitive technologies can miss a significant subset of patients who may benefit from targeted therapy.

PIK3CA
Identifying patients with PIK3CA mutations who derive benefit from PI3K-targeted therapy could help guide treatment decisions. The BELLE-2 trial showed that a noninvasive ctDNA technique, such as SafeSEQ, can be used for detection of PIK3CA mutations might provide a more accurate measure of mutational status and heterogeneity over time and treatment, compared with archival tuzmor tissue.2

ESR1
Mediated resistance to endocrine therapy —SafeSEQ overcomes the challenges of detecting subclonal presence of ESR1 mutations, a primary mechanism of resistance to aromatase inhibitors. These mutations are particularly difficult to detect if they are missed in a local biopsy or if few tumor-mutant molecules are in circulation and cannot be detected by a less sensitive technology.3

AKT1
Comprehensive profiling of AKT1-E17K may help define a potential role for the mutation in the development and progression of breast cancer.4

Monitor treatment response and disease dynamics:
Molecular alterations that may evolve under the influence of treatment exposure. By accurately monitoring disease response and clonal dynamics, SafeSEQ enables the informed adaptation of therapeutic strategies.5

Minimal residual disease (MRD) detection and recurrence surveillance:
Detects prevalent driver mutations (e.g., PIK3CA and TP53) with exquisite sensitivity.6

The SafeSEQ Breast Cancer panel is validated under CLIA conditions and can be used to support clinical trials.

References

  1. Rugo, H.S. et al. (2019, April). Palbociclib in combination with fulvestrant or tamoxifen as treatment for hormone receptor positive metastatic breast cancer with prior chemotherapy for advanced disease (TBCRC 035): A Phase II study with pharmacodynamic markers. Presented at the American Association of Cancer Research annual conference, Atlanta, Georgia
  2. Baselga J, Seock-Ah I,  Iwata H, Cortés J, et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:904-916. 
  3. Spoerke J, Gendreau S, Walter K, Qiu J, et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. NatCommun. 2016;7:11579.. 
  4. Rudolph M, Anzeneder T, Shulz A, Beckmann G, et al. AKT1 E17K mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection. BMC Cancer. 2016;16:622. doi:10.1186/ s12885-016-2626-1.
  5. Dawson SJ, Tsui DW, Murtaza M, Biggs H,  et al. Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer. N Engl J Med. 2013;368:1199-209. doi:10.1056/NEJMoa1213261.
  6. Rodriguez BJ, Córdoba G, Aranda A, Álvarez M,  et al. Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis. J Clin Med. 2019;8(8):1188. doi: 10.3390/jcm8081183.

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