Breast cancer risk is usually defined in terms of relative risk. In this definition, the relative risk of breast cancer is the risk of breast cancer occurring relative to the average risk. So when it is suggested that someone is at increased risk, it usually means increased risk relative to average. For example, the average risk of breast cancer occurring in a woman between the ages of 20 and 80 is about 12% or 1 in 8. This figure is the absolute, cumulative risk over many years. If you have a mother or sister affected by breast cancer, the same risk is about 18% or 1.5 times the average. So, the woman with a sister with breast cancer is at increased relative risk compared to average but the absolute risk is not high relative to 100%. The Gail Model can be used to calculate an individual’s absolute risk based on several risk factors. This risk can then be compared to average. Research has shown that many women do not accurately understand their risk and this model can be helpful towards this end. Unfortunately, risk is just a statistic and does not tell us who will develop breast cancer. For most women, our knowledge about risk factors is extremely lacking. This is best exemplified by the fact that about 75% of the women who get breast cancer every year have none of the significant risk factors. Only women with mutations of BRCA I or II genes can be more accurately predicted to develop breast cancer.
The Gail Model was developed at the National Cancer Institute as an aid to estimate an individual women’s risk of breast cancer. This tool can be useful to most women, but should not be applied to women with the known genetic mutations, BRCA I or II, whose risk is estimated by other means. The model is available at http://www.cancer.gov/bcrisktool/.
BRCA I/II Genetic Mutations
Breast cancer is not a single entity but a diverse group of cancers which affect the breast. Each of these separate breast cancers likely has a diverse set of factors or contributors to it’s development. One of the important factors which predisposes a woman to breast cancer are abnormal genes or mutations. These mutations can be inherited from either parent or develop in previously normal genes as we age. There is still much to learn about which genes are involved in the development of breast cancer, and even more challenging, is how they contribute to malignant change in the breast. The best known inherited mutations are abnormalities of two genes called BRCA I and BRCA II. When these genes are abnormal, a woman has an approximately 80% risk of developing breast cancer before age 50 and a risk of getting ovarian cancer of about 20-60% in her lifetime. These numbers are enormously elevated over the average lifetime risk for breast cancer of about 12% and for ovarian cancer of approximately 1%.
We can test for these mutations using a sample of blood. The test itself is a very complex and highly technical procedure which sequences the DNA and analyzes for over several hundred possible mutations. This makes testing for unknown mutations in an individual very expensive.
If there is a mutation known to exist in a family, testing is simplified and much less expensive. Interpretation and management of test results, including negative results is an extremely complex process and requires the effort of health care professionals experienced in this area such as genetic counselors, genetic nurse specialists, and breast care specialists.
Women who have had breast cancer have a estimated 5% risk of developing a second breast cancer within 5 years of their first diagnosis and a 25% risk by age 70. Women who have had breast cancer AND carry a mutation in BRCA1 or BRCA2 have a 25 % risk of developing a second breast cancer within 5 years of their diagnosis and about a 64% risk by age 70.
Men and women who carry an altered BRCA1 or BRCA2 gene have a slightly increased likelihood of developing colon, stomach, and pancreatic cancer. Men specifically have a slightly increased risk of prostate and breast cancer.
Atypical Ductal/Lobular Hyperplasia (ADH/ALH)
ADH/ALH represent changes in the breast tissue which reflect a significantly increased risk of breast cancer (about 3X average). These changes are usually discovered incidentally at the time of biopsy for microcalcifications on a mammogram or benign lumps. These findings are often referred to as borderline lesions of the breast and make up about 1-2% of all biopsies. The presence of these changes is one of the better indicators of risk as the finding is specific to the individual and more than just a statistical indicator of risk in a population.
After a discovery of ADH/ALH on a needle core biopsy, an excision surgically of more tissue is generally recommended. This is due to the fact that upon re-excision, Ductal Carcinoma-In-Situ (DCIS), which are pre-cancerous lesions, will be found on microscopic examination and will require different treatment than ADH/ALH.