AnteBC – Breast Cancer

Science behind AnteBC

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

AnteBC is a genetic test that assesses a woman’s personalized risk of 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 by the healthcare and biotechnology company Antegenes (License number L04685) and is registered CE-marked medical device (IVD).

AnteBC test uses data from single nucleotide polymorphisms (SNPs) in the genome to evaluate the personalized risk of 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 risk of developing breast cancer.

The risk model is based on peer-reviewed international research and has been evaluated and validated using anonymous population data of the Estonian Biobank and the UK Biobank.

AnteBC is used to determine the number of genetic variants that affect a patient’s individual risk and results in a combined genetic risk assessment. The patient’s personal risk is compared with the rest of the population, evaluating the 10-year probability of developing the disease and relative risk compared to the average genetic risk in the population, which is used to interpret the test results together with clinical recommendations.

Recommendations based on the relative risk calculated using the AnteBC test consider only the polygenic risk component. In addition to test results, recommendations include clinical information about other risk factors that are not considered in the test but can still be used.

Target Population

AnteBC test is recommended for:

  • Women between the ages of 30 and 75 of European origin (Note: Genetic risk studies used by AnteBC have been conducted in populations of European descent).

The AnteBC test is not recommended if any of the following significant risk factors occur:

  • The patient has been diagnosed with atypical breast hyperplasia or in situ carcinoma;
  • A monogenic mutation significantly increasing the risk of breast cancer has been identified in the patient or the biological relatives of the patient, for example, BRCA1, BRCA2, CHEK2, PALB2, ATM, TP53, CDH1, STK11, and others.

Indications for testing for the monogenic mutations: 

  • The patient’s biological relative has a monogenic mutation in hereditary breast and ovarian cancer gene (BRCA1, BRCA2).
  • 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;
  • Biological relatives have had three or more tumors associated with hereditary cancer syndromes;
  • Ashkenazi Jewish origin.

If any of these these criteria are met, we recommend genetic counseling and, where appropriate, testing for hereditary forms of cancer.

AnteBC Test Development

Population distribution of the polygenic risk score and risk differentiation were validated using anonymous data from the Estonian Biobank and the UK Biobank. Based on large-scale genetic data, various risk prediction models published in the international scientific literature were tested, and the prediction accuracy of the best performing model was evaluated on independent data. Based on the selected risk score, the population distribution on which the comparisons are based on was also created.

The risk score underlying AnteBC (Mavaddat et al., 2019) (1) is tailored for practical use and independently validated. After validation, AnteBC uses 2803 breast cancer-related SNPs to calculate personalized risk scores.

Interpretations based on individual risk scores are dependent on 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 assessed during validation on biobanks data. The patient’s 10-year population-based risk is calculated using Choudhury et al. absolute risk assessment model (2). The model uses the estimation of risk differentiation from validation using the Estonian Biobank data as input. AnteBC was additionally evaluated using anonymous genetic data from the UK biobank.

In addition, we use specific population-based overall mortality and breast cancer morbidity and mortality data to assess risks.

Clinical recommendations in AnteBC test are based on evidence-based data on breast cancer risk factors, screening, and preventive measures, and the corresponding recommendations of international medical organizations, which are tailored to the individual risk level resulting 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 using second-generation genotyping and carried out in the Core Facility of the Institute of Genomics, University of Tartu, which is certified by Illumina CSPro (Certified Service Provider). The Illumina Global Screening Array-24 (GSA) v3.0 chip and Illumina iSCAN sequencer are used for genotyping. The GSA chip has  ̴̴762,000 markers. The whole analysis is performed according to the Illumina Infinium HTS (high-throughput screening) protocol (Illumina Inc, http://www.illumina.com; Document # 15045738 v04).

Quality-controlled markers resulting from genotyping are imputed using a 1000G panel with reference to the human genome GRCh37. Based on imputed genotype data, an individual risk score is calculated in the Antegenes Information System.

The test report is made available to the patient and their treating physician. Interpretation of the results and clinical recommendations are added to the report.

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 genes that significantly increase the risk of breast cancer, such as BRCA1, BRCA2, CHEK2, PALB2, ATM, TP53, CDH1, STK11, and others.
  • 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.

Cost of the test

Please see the “Customer Price List“.

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.