deCODE BreastCancer™
The first test measuring genetic risk of the common forms of breast cancer. Complements standard risk modeling tools. More complete assessment of risk and more personalized and effective screening, prevention and treatment.
Better screening & prevention
How can deCODE BreastCancer™ help?
Comprehensive risk assessment
deCODE BreastCancer™ detects genetic risk that is independent of and complementary to the risk factors used in standard clinical risk assessment tools. The results are presented as a numerical value of individual risk relative to the population average, by which the scores of traditional risk modeling tools can be multiplied.
Informing prophylactic therapy
Approximately 14% of women of European descent aged 55 and older who take the deCODE BreastCancer™ test will receive a score placing them at or above a 1.7% absolute risk of developing breast cancer within the following five years. This is the threshold used by the American Society of Clinical Oncology for consideration of the use of tamoxifen (or similar drugs) as preventive therapy. deCODE BreastCancer™ also provides information on whether a woman is more likely to develop estrogen-positive or estrogen-negative breast cancer.
Modification of BRCA-associated risk
The risk conferred by four of the SNPs detected by the deCODE BreastCancer™ test interacts in a multiplicative manner with that conferred by the highly penetrant mutations in the BRCA1 and BRCA2 genes. The results can thereby indicate increased lifetime risk in women positive for the BRCA1 or BRCA2 gene mutations.
Clinically relevant risk for a significant proportion of women
deCODE BreastCancer™ detects genetic risk that is independent of and complementary to that measured by standard clinical risk assessment tools. The results are presented as a numerical score of individual risk relative to the population average. Multiplying this number by risk as modelled by traditional factors yields a more comprehensive risk score.
The range of the deCODE BreastCancer™ test is 0.4 to 7.5 fold the average population risk, meaning the lowest and highest genetic risk results obtainable by the test. The lowest and highest risk results are obtained for those who are homozygous for all the non-risk or risk alleles respectively. For women of East Asian descent the range of the test results is 0.5 to 2.5 fold their population average risk.
Approximately 6% of women of European descent will have results ≥ 1.65-times the general population risk (65% higher risk). This corresponds to a 20% or greater lifetime risk, the threshold at which the American Cancer Society (ACS) recommends annual breast MRIs in addition to mammograms.
A further 10% of women of European descent will receive a score putting them at a 15-20% lifetime risk, a range within which ACS considers the benefits of MRI screening should be considered.
Some 2% of women of European descent will receive a score of 2.0 or greater, a doubling of the population average lifetime risk of breast cancer.
Genotype combinations that convey extreme risks are very rare. For example genotype combinations that give risk greater than 5.0 are only found in 1:900.000 individuals of European descent. Even though the risk associated with each individual genetic marker is thoroughly validated and highly significant, the multiplicative relative risk values calculated for very rarely occurring risk genotype combinations should be used only with a great degree of caution for modifying individual assessed risk.
Each of the SNPs measured by deCODE BreastCancer™ has only a modest impact on risk. However, because they are common and their effect is multiplicative, deCODE BreastCancer™ is detecting risk contributing to the majority of breast cancer cases.
Modifying effect
Because deCODE BreastCancer™ results are independent of other known risk factors for breast cancer,- such as age, family history, age at menarche, child births, and hormonal therapy and status — the risk scores from these factors or as combined in established risk assessment tolls, like the Gail score, can be multiplied by the test results to yield a more comprehensive risk score. Thus, women whose risk as assessed by standard criteria, may not reach ACS or ASCO guidelines for moderate or high risk may reach these thresholds once the results of deCODE BreastCancer™ are factored in. As a result, the composite risk may be useful to help decide whether additional screening with MRI or Tamoxifen prophylaxis may be appropriate and should be considered according to these guidelines.
Relevance of family history
deCODE BreastCancer™ detects genetic risk factors for the common forms of breast cancer and the risk measured by the test is essentially independent of the risk conferred by family history of the disease.
deCODE BreastCancer™ is not a BRCA test and does not detect the mutations known to cause what commonly is referred to as “familial breast cancer”.
Whereas 70-80% of women have no family history of breast cancer, 20-30% have one ore more relative with breast cancer. Because of the independence of familial history the deCODE BreastCancer™ results can be used to modify the risk of women in both groups. It is important to note that there are rarer genetic risk factors for breast cancer still to be discovered and neither deCODE BreastCancer™ nor the BRCA tests, alone or in combination, account for all of the genetic risk for breast cancer. Quantifiable non-BRCA familial risks, as factored into common risk modeling, can therefore be multiplied by the risk results of the deCODE BreastCancer™ test for calculation of a more complete genetic and lifetime risk.
Modification of BRCA1/BRCA2 risk
The variants on 5q11, 10q26, and 16q12 detected by deCODE BreastCancer™ have been shown to modulate the risk conferred by the high-penetrance mutations in the BRCA2 gene(12,25). The variant on 16q12 has also been shown to modulate the risk of breast cancer in subjects who are carriers of high-penetrance mutations in the BRCA1 gene. The modifying effect conferred by the SNPs in the deCODE BreastCancer™ test impacts the risk of the BRCA1 and BRCA2 mutations in a multiplicative manner, and the test report provides the factors by which the BRCA risk should be multiplied in order to more accurately assess BRCA-associated risk. The modifying effect may be as high as 1.14 fold or 1.62 fold for BRCA1 and BRCA2 mutation carriers respectively. On their own, the deCODE BreastCancer™ results never confer sufficiently high risk to form the basis for recommending risk-reducing surgical intervention. However, because some of the SNPs can increase the risk conferred by mutations in the BRCA1 and/or BRCA2 genes, the deCODE BreastCancer™ test can be used as an aid to clinical decision making in conjunction with a BRCA1 or BRCA2 genetic test.
Prediction of estrogen receptor status
Five of the 16 SNPs (on 2q35, 5p12, 8q24, 10q26, and 16q12) measured by deCODE BreastCancer™ are associated with increased risk not only of breast cancer, but also of the likelihood that if a woman does develop breast cancer that she will develop estrogen receptor-positive(ER+)tumors (1,2,5,14,29,30,31). The probability of developing ER+ breast cancer as determined by deCODE BreastCancer™ ranges from 55.6% for subjects who are homozygous (carry two copies) of the non-risk versions of all five SNPs, to 91.3% for those who are homozygous for the at-risk versions of all five SNPs at all 5 markers.
Subjects at higher risk of breast cancer, particularly estrogen receptor-positive breast cancer, may benefit from preventative hormonal therapy with a selective estrogen response modifier (SERM) such as tamoxifen or similar compounds. According to ACS guidelines, most women aged 60 or over have a sufficiently high risk of breast cancer to be considered for tamoxifen therapy as preventative therapy. Women under 60, if they have substantial genetic and non-genetic risk factors, may also be considered for such preventive therapy. Furthermore, some forms of hormone replacement therapy (HRT) have been reported to increase risks of ER+ breast cancer. deCODE BreastCancer™ can therefore assist in clinical decision-making regarding both prophylactic SERM and HRT therapy.
This content was last reviewed on April 07, 2011.