1. Breast Cancer Ten percent of breast cancer is hereditary. Or 23,000 women a year with a genetic basis for their cancer. The most common mutations in this group are BRCA1 and BRCA2 - comprising roughly 7% of all breast cancer. These two proteins are part of a DNA process called “homologous repair”.

3. If the DNA repair process malfunctions then DNA errors accumulate. This leads to cancer formation. In BRCA1 the cancers are predominantly breast and ovarian. In BRCA2 the cancers are female and male breast, ovarian, prostate, and in some families pancreatic.

4. The risk of cancer differs between BRCA 1 and 2. A meta-analysis of ten studies conducted both in high-risk clinics and population-based settings reported that the cumulative risk of breast cancer by age 70 years was 57% for BRCA1 and 49% for BRCA2. Ovarian cancer risk was 40% for BRCA1 and 15% for BRCA2. Male breast risk is 10% for BRCA2 and 1% for BRCA1. Prostate cancer - 5 to 7 fold increased risk for BRCA2 and 1.8 fold increased risk for BRCA1.

5. In general we use the following guidelines to identify carriers

6. Today BRCA testing should include the search for both mutations and large rearrangements. Mutations are misspellings of the DNA sequence and large rearrangements are errors that occur when DNA replicates and some of the sequence is left out. The testing for large rearrangements is also known as BART –BRACAnalysis® Large Rearrangement Test

7. As you can see BRCA1 and 2 make up most of the genes associated with breast but several others make up the remaining 3%

9. Some gene mutations are associated with well defined clinical pictures such as Li-Fraumeni and Peutz-Jeghers Syndrome. Others are still being explored, such as CHEK2 and PALB2. If you are negative for BRCA1 or 2, you may have one of these other gene mutations. To pursue this there are “Reflex Panels” that contain all these genes in one test and you may be a candidate for this type of testing.

10. Breast cancer is our most common problem and a good family history is key in determining if you have a genetic reason for breast cancer in your family. Details about your family history that you might not think are important may make the difference between whether or not you qualify for testing. We use several models to calculate your risk – such as Upenn, Tyrer-Cuzick, Gail, Myriad. If you have a genetic mutation we will give you information that will help you make decisions for you, your children and your extended family.