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.

Breast cancer is by far the most common cancer in women worldwide.

Current global incidence of breast cancer is in excess of 1,151,000 new cases diagnosed each year. Breast cancer incidence is highest in developed countries, particularly among populations of Northern European ethnic origin, and is increasing. In the United States, the annual age-standardized incidence rate is approximately 125 cases per 100,000, more than 3 times the world average. Rates in Northern European countries are similarly high. In 2008 it is estimated that 184,450 new cases of invasive breast cancer will be diagnosed in the United States and 40,930 people will die from the disease. To this figure must be added the 67,770 ductal- and lobular-carcinoma in-situ diagnoses expected in 2008. From an individual perspective, the lifetime probability of developing breast cancer is 12.3% in US women (ie, 1 in 8 women will develop breast cancer during their lives). As with most cancers, early detection and appropriate treatment are important factors. Overall, the 5-year survival rate for breast cancer in the United States is 89%. However, in individuals presenting with regionally invasive or metastatic disease, the rate declines to 84% and 27%, respectively.

Increasingly, emphasis is falling on identifying individuals who are at high risk for breast cancer. Such individuals can be managed by more intensive screening, preventative chemotherapies, hormonal therapies, and, in cases of individuals at extremely high risk, prophylactic surgery. Large-scale screening programs constitute a huge economic burden on health services, while preventative therapies have associated risks and quality-of-life consequences. The overall goal of breast cancer risk assessment is to provide a rational framework for the development of personalized medical management strategies for all women, with the aim of increasing survival and quality of life in high-risk women while minimizing costs, unnecessary interventions, and anxiety in women at lower risk.

Early diagnosis and primary prevention are crucial to breast cancer control. The deCODE BreastCancer™ test is an important and significant additional risk factor identifier that should be taken into account when deciding on optimal strategies for the screening and prevention of breast cancer.

Familiality of breast cancer

Altogether about 20 to 30% of women who get breast cancer have a family member with the disease, meaning that 70 to 80% do not have a family history of breast cancer. Women who have a first-degree relative with breast cancer are twice as likely as the general population to develop the disease themselves. This indicates that genetic predisposition plays a significant role in determining who gets breast cancer and who does not.

Only a portion of family history-positive breast cancer patients (up to 25%; 2 to 5% of all breast cancer cases) have identifiable genetic mutations in the BRCA1, BRCA2, TP53, and PTEN genes, which, when inherited from one’s parents, are highly likely to cause breast cancer. These individuals usually have a strong family history of breast cancer, particularly of early-onset and/or ovarian cancer cases. However, each of these mutations is very rare, occurring in only a very small fraction of cases.

The deCODE BreastCancer™ test does not include or detect these rare mutations. However, some of the variants in the deCODE BreastCancer™ test modify the risk of breast cancer in subjects who carry mutations in the BRCA1 and/or BRCA2 genes. The deCODE BreastCancer™ test reports a factor based on the relevant SNP genotypes by which the lifetime risk from the BRCA mutation should be multiplied in order to determine the overall lifetime genetic risk of breast cancer, given that the subject is diagnosed as a carrier of a high-penetrance BRCA1 or BRCA2 mutation.

Then there are the 15 to 20 % of breast cancer cases that have 1 or more close relatives with breast cancer but do not have mutations in the BRCA1, BRCA2, TP53, and PTEN genes. These patients may have hereto unidentified genetic variants. The risk identified by the deCODE BreastCancer™ test seems to be largely independent of immediate family history, i.e., the risk markers identified account for only a small portion (about 5%) of these familial cases. This fact makes the deCODE BreastCancer™ test all the more relevant for this group of patients since their increased baseline risk caused by their family history, and as assessed by some of the models available, can be multiplied with the test results.

The majority (70 to 80%) of breast cancer cases arise in individuals who do not have a noticeable family history of breast cancer but who may still be genetically predisposed to develop breast cancer. The genetic predisposition variants they inherit may be so common in the population, of such a number, and each with such a relatively small effect, that their contribution to breast cancer generally surfaces in sporadic cases. On an individual basis however, women who have several of these genetic risk variants are at substantially increased risk relative to the population. The deCODE BreastCancer™ test is designed to assess the genetic risk of the common form of breast cancer by testing for multiple risk variants that are common in the population.

In basic terms, carrying a high-risk deCODE BreastCancer™ genetic profile does not necessarily mean that the subject will develop breast cancer, just as having a low-risk genetic profile does not eliminate the possibility of getting the disease. Rather, these genetic risk variants impact the likelihood that the subject will develop breast cancer. Nongenetic risk factors such as current age, age at menarche, age at first live birth, hormonal history and status, history of exposure of the chest wall to X-rays, and previous benign or malignant breast disease may also affect a subject’s risk of breast cancer. Genetic and nongenetic risk factors all need to be taken into account when judging the overall breast cancer risk of an individual.

This content was last reviewed on March 16, 2011.