AnteBC – Breast Cancer Polygenic Risk Score Test

Science behind AnteBC

  • E-mail: info@antegenes.com
  • Phone number: +372 5377 8141

Overview and Purpose of the AnteBC Test

AnteBC is a genetic test that assesses a woman’s personalized risk of developing breast cancer using a polygenic risk score. The purpose of the AnteBC test is to reduce the risk of premature mortality due to breast cancer through advanced breast cancer screening and other preventive measures.

AnteBC has been developed as a laboratory test by healthcare and medtech company Antegenes (License number L04685).

AnteBC is registered as the medical device (IVD) in Estonian Medical Devices Database (EMDDB code: 14726).

AnteBC test uses data from genome-wide single nucleotide polymorphisms (SNPs) to evaluate individual polygenic risks of developing breast cancer. This approach is based on the technology of polygenic risk scores. SNPs used in the risk score either increase or decrease the risk. AnteBC combines the number of risk-increasing and lowering SNPs in the genome and their effects, which are summed up to form an overall estimate. Each SNP has little impact on the overall risk of breast cancer but combining the effects of individual SNPs contributes to a clinically significant assessment of the total risk. The risk model is based on peer-reviewed international research and has been evaluated and validated using anonymous population data in the Estonian Biobank and UK Biobank. 

AnteBC is used to determine the carrier status of genetic variants that affect patient’s individual risk and are combined into a polygenic risk assessment and the 10-year probability of developing the disease. Individual patient risk is put into context with the population background data and estimates about the genetic risks of individuals of the same sex, age and nationality. Individual test results are accompanied with actionable follow-up recommendations. The final report also includes information about other clinical risk factors that are not included in the polygenic risk estimation.

The test report is made available to the patient and submitted to the Estonian E-Health system. If the patient has been referred to Antegenes by a healthcare service provider then the results can also be shared with the treating physician.

Target Population

AnteBC test is recommended for women between the ages of 30 and 75 of primarily European ancestry. Genetic risk studies used by AnteBC have been conducted in populations of European descent.

AnteBC Test Development

The polygenic risk scores and their risk differentiation estimations were validated using anonymous data from the Estonian Biobank and UK Biobank. Based on large-scale genetic data, various risk prediction models published in the international scientific literature were compared, and the prediction accuracy of the best performing model was evaluated on independent data.

The risk score underlying AnteBC was adapted and independently validated for practical use based on Mavaddat et al. (2019) (1). AnteBC uses 2803 breast cancer-related SNPs to estimate personalized risk scores.

Interpretations based on individual risk scores are dependent on the underlying population data. AnteBC estimates the distribution of individual risk levels relative to the rest of the population, using the population distribution and the risk differentiation between patients included in validation. The patient’s 10-year population-based risk is estimated using Choudhury et al. absolute risk model (2). The absolute risk model applies the risk differentiation estimates from Estonian Biobank. The absolute risk model additionally uses patient sex, age and country based epidemiological background including overall breast cancer incidence and morbidity, and overall mortality information.

Clinical recommendations of AnteBC are based on evidence-based data on breast cancer risk factors, screening, and prevention measures, and the corresponding recommendations of international organizations that are tailored to the individual risk estimates from the test.

AnteBC Test Methodology

AnteBC test uses a non-invasive buccal swab method to collect and isolate patient’s DNA.

The genetic material is analyzed either using second-generation genotyping or sequencing based methods. The standard procedure includes the use of Illumina Global Screening Array-24 (GSA) v3.0 chip and Illumina iSCAN sequencer for genotyping. This workflow genotypes the ~762 000 markers on the GSA chip by following the Illumina Infinium HTS (high-throughput screening) protocol (Illumina Inc, http://www.illumina.com; Document # 15045738 v04).

The test can also use information from other microarrays and sequencing approaches that output DNA data broadly covering the human genome.

Antegenes performs the risk assessment based on imputed genotype data. Quality-controlled markers resulting from genotyping are imputed using a 1000G panel with reference to the human genome GRCh37.

AnteBC Test Limitations

  • AnteBC test is not used to diagnose breast cancer.
  • AnteBC test is not validated for use by individuals of non-European descent.
  • An elevated risk estimated by the AnteBC test does not mean that the patient will develop breast cancer during their lifetime. Also, a moderate or lower risk does not mean that the patient will not develop the disease.
  • AnteBC test is patient-specific and does not assess the risk of the patient’s family and relatives, i.e.polygenic risk score-based disease risks may not be transmitted directly from parents to children.
  • AnteBC test does not analyze rare pathogenic mutations in single genes that significantly increase the risk of breast cancer, such as BRCA1, BRCA2, CHEK2, PALB2, ATM, TP53, CDH1, STK11, and others. Therefore, we recommend additional counseling and testing for the monogenic mutations, if:
    1. The patient has been diagnosed with breast cancer, ovarian cancer or pancreatic cancer.
    2. The patient’s biological relative has a monogenic mutation in hereditary breast and ovarian cancer gene (BRCA1, BRCA2).
    3. A first- or second-degree biological relative has been diagnosed with breast cancer below 45 years of age, male breast cancer, pancreatic cancer, ovarian cancer, metastatic prostate cancer, or two or more cases of breast cancer in one person.
    4. The patient’s biological relatives have had three or more tumors associated with hereditary cancer syndromes.
    5. Ashkenazi Jewish origin.
  • The AnteBC test is based on the most up-to-date scientific data, which may, however, be supplemented and changed in the future as additional information becomes available. The field of genetics is constantly evolving, which may lead to changes in risk assessments over time, as well as changes in test selection recommendations and clinical recommendations based on test results.
  • Different polygenic risk scores predicting risks of the same trait may give different estimates of the individual’s risks due to differences in the genetic variants included in the models and their weights.
  • The results of this test should be applied in context with other relevant clinical data. In addition to the possible genetic predisposition, other risk factors also influence the risk of breast cancer.
  • Additional Information:

    Antegenes
    E-mail: info@antegenes.com
    Address: Raatuse 77, 50603 Tartu
    Phone number: + +372 5377 8141
    www.antegenes.com

    References

    1. Mavaddat N, Michailidou K, Dennis J, Lush M, Fachal L, Lee A, et al. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am J Hum Genet. 2019;104(1):21-34.
    2. Choudhury PP, Maas P, Wilcox A, Wheeler W, Brook M, Check D, et al. iCARE: R package to build, validate and apply absolute risk models. bioRxiv. 2018:079954.