Background:
About 13 percent of women in the general population of the United States will develop breast cancer sometime during their lifetime and it is the most common cancer in women (American Cancer Society 2024). About 5-10% of breast cancer cases are thought to be hereditary. The Inherited Breast Cancer Panel is a next-generation sequencing test that detects variants in the coding regions of 14 genes associated with increased risk for breast cancer. The results from this genetic test can facilitate risk assessment for patients and lead to more efficient and appropriate medical management including treatment and surveillance strategies. It is recommended that this testing be accompanied by a complete family history and genetic counseling.
Reasons for Referral:
- Confirmation of a clinical diagnosis of an inherited breast cancer.
- Testing for individuals with a positive family history for inherited breast cancer (targeted testing is available if familial mutation is known).
Methodology:
Next generation sequencing will analyze the exons or coding regions of 14 inherited breast cancer-associated genes using Illumina NextSeq 500/550 technology and preparing samples using hybridization probes to enrich exonic regions.
This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats-these regions may contain variant that impact gene function.
Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version 4.1.4.1. A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.
The 14 inherited breast cancer-associated genes are listed below:
ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53
Specimen Requirements:
Blood: EDTA or ACD (Solution A or B):
- Adult: 5 mL
- Child: 2-3mL
- Infant: 1-2mL
Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.
Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.
Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks
DNA: 5-10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS).
For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion. For extraordinary circumstances, where testing must be performed within the above windows, please contact the laboratory.
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.
Test Performed (Days):
Weekly
Turn Around Time:
5 weeks
Shipment Sensitivity Requirements:
- Package and ship specimen to remain cold, but not frozen.
- Ship via overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping kits and instructions at (855) 535-1522.
References:
Additional Info: