GENETIC TESTING FOR BREAST CANCER

By Joginder Singh, M.D.

Breast Cancer is a common cancer. One in 9 women will have breast cancer in their lifetime. Most women are scared of the hereditary nature of breast cancer. They would like to know the chances of breast cancer in their siblings and children. It should be noted that most breast cancers are sporadic and no hereditary cause is found. Only 7-10% of breast cancers are due to hereditary factors. Major causes of hereditary breast cancer are due to alterations of genes BRCA1 and BRCA2.

What are BRCA1 and BRCA2 mutation?
Every human cell (except red blood cells) has a nucleus, which has 23 pairs of chromosomes. Chromosomes contain DNA (Deoxyribonucleic acid). DNA exists as two long paired strands spiraled into a double helix. Each strand is made up of millions of chemical building blocks called bases. There are only four different chemical bases in DNA (Adenine, Thymine, Cytosine, Guanine) but they can be arranged and rearranged in countless ways. The order in which bases occur determine the message to be conveyed much as specific letters of the alphabet combine to form words and sentences. Cell function is determined by protein and structure of proteins and function depends on structure of DNA. If there is mutation or change in normal base pair sequence in DNA proteins formed may not function or function differently. It should be noted, that some mutations are silent. Like the words GRAY and GREY are different but mean the same. However, if you change GRAY and GREY to GRZY, it does not mean anything and the protein may not function. BRCA is located on chromosome 17 and BRCA2 is located on chromosome 13. 500 different mutations have been found in BRCA1 and 300 in BRCA2, however, many mutations are silent and some are of unknown significance.

Who should be tested?
​Because these tests have implications not only on the individual being tested but also on the whole family, the individual being tested should be given detailed information about the risks and benefits of testing.

Features that increase likelihood of having BRCA mutation are:
1. Multiple cases of early onset breast cancer.
2. History of ovarian cancer in same family.
3. Breast and ovarian cancer in
4. same woman.
5. History of bilateral breast cancer.
6. Ashkanezi Jewish heritage since there is a higher incidence of a particular mutation in those families.
7. Male breast cancer.

Pattern of Inheritance
These mutations are transmitted by autosomal dominant inheritance, which means that they are transmitted equally by males and females. 50% of offspring’s of affected persons will carry the mutation; it does not depend on sex. It is a very common misunderstanding among patients that inheritance only comes from mother, whereas fathers transmit genes equally.

What can be done if BRCA mutation is found?
1. Monthly breast examinations starting at the age of 18.
2. Clinical exam every 6 months beginning at age 25.
3. Mammograms and MRI of breast beginning at age 25 or individualized depending on the age of the youngest relative with cancer. MRI is more sensitive than mammograms in mutation carriers.
4. Prophylactic mastectomy decreases risk of breast cancer by more than 90%.
5. Prophylactic oophorectomy (removal of ovaries) after childbearing age decreases risk of both breast and ovary cancer.
6. Tamoxifen or Raloxifene considered chemoprevention could be considered.

Benefits of gene testing:
1. Gives relief when tests are negative.
2. Intervention can be done to prevent cancer if results are positive.
3. Informed decisions and fewer check ups.

Limitations of testing:
1. Psychological distress if positive.
2. Some mutations may never lead to cancer, but give distress because we may never know the meaning of such variation such as GRAY and GREY words.
3. Insurance issues even though there are laws against insurance discrimination.

The decision to undergo testing should be personal and voluntary. These tests should not be done to please relatives, friends, children, siblings, or health care providers.


​


​

​ 

---

Read Full Newsletter