About Breast Cancer
Breast cancer is a malignant tumor that usually arises from the cells lining the milk ducts in the breast or in the lobules at the ends of the ducts. The precise causes of breast cancer are not known, however the major classes of known risks are hormonal factors and genetics. Early diagnosis and effective treatment are key to winning the battle against breast cancer.
Breast cancer is by far the most common cancer in women worldwide. In the United States, approximately 1 in 8 women will develop breast cancer at some point in their lives. The chance of dying from breast cancer is a lot lower, around 1 in 35, and breast cancer survival statistics are steadily improving over time. 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. From an individual perspective, the lifetime probability of developing breast cancer is 12.3% in
American women.
Not all women are at equal risk of getting breast cancer. In addition to increasing age, the primary factors that determine risk for breast cancer are related to hormonal factors and genetics. A substantial proportion of the breast cancer cases that occur in developed countries can be explained by factors that influence the amount of lifetime exposure to estrogen, including reproductive and hormonal factors, obesity, alcohol, and physical activity. Genetic factors are also important as can be seen by the fact that women who have a mother or a sister with breast cancer are twice as likely as the general population to develop breast cancer themselves.
The genetics 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 (mother or sister) 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.
The genetics of breast cancer has 3 main presentations:
- Hereditary or familial form of breast cancer segregating within families.
- Families with as few as 2 cases and not with strong enough genetic effect to be obviously segregating as a hereditary condition.
- Sporadic breast cancer, no family history of the disease.
In fact numbers 2 and 3 above may be difficult to distinguish since breast cancer is so common that most families will have 1 or more affected with the disease and it is often just a matter of the number of women and the degree of relatedness that are assessed that determine how many breast cancers will be ascertained in a family. Still there seems to be a measurable difference in the number and degree of relatives affected for estimation of risk in different modeling tools based measures of risk associated with positive family history and other recognized risk factors (see for example the Gail score model at http://www.cancer.gov/bcrisktool/).
Hereditary breast cancer
Only a portion of patients with a family history of breast cancer (less than 25%; 2 to 5% of all breast cancer cases) have what qualifies as the highly heritable or familial form of breast cancer caused by identifiable genetic mutations in the BRCA1, BRCA2, TP53, and PTEN genes. 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 breast cancer cases. The deCODE BreastCancer™ test does not include or detect these rare mutations. However some of the variants in the deCODE BreastCancer™ test modulate 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.
Breast cancer cases with a not so noticeable family history
15 to 20 % of breast cancer cases have 1 or more close relatives with breast cancer but do not have so strong or characteristic family history as to be recognized as hereditary or familial, nor do they have mutations in the BRCA1, BRCA2, TP53, and PTEN genes. These patients may have heretofore unidentified genetic variants. The risk identified by the deCODE BreastCancer™ test seems to be largely independent of immediate family history, ie, the risk markers identified account for only a small portion (about 5%) of these familial cases. Thus the common genetic variants tested by the deCODE BreastCancer™ test do not explain risk due to family history of breast cancer. In fact, numerous studies have shown that the risk is independent of family history. 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 by the test results.
Sporadic breast cancer
The majority (70 to 80%) of breast cancer cases arise in individuals who do not have a noticeable family history of breast cancer. This does not mean that these women are not genetically predisposed to develop breast cancer. The genetic predisposition variants they inherit may be so common in the population, of such a small number and each with such a relatively small effect, that their contribution to breast cancer generally surfaces as sporadic cases. On an individual basis however, women who have several of these genetic risk variants are at a 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 and is especially useful in the 70 to 80% of the population that does not have a family history of breast cancer.
Collectively, the deCODE BreastCancer™ markers account for about 60% of the population attributable risk, meaning that if we were able to prevent all breast cancer cases in women that have increased risk relative to the general population according to the deCODE BreastCancer™ test, 60% of breast cancer would be eliminated.
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 patient.
Breast cancer screening
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.
For further and more complete information about breast cancer see the American Cancer Society web site on detailed guide on breast cancer here.