Angelina Jolie Masectomy: What Are BRCA Mutations?

In May, Angelina Jolie began a global discussion on preventative therapies towards breast and ovarian cancer with the revelation that she underwent a double mastectomy earlier this year. Her op-ed in the New York Times showed a strong and brave woman taking control of her own personal health, but understanding the more molecular details is incredibly important as the world processes how this might relate to them and their loved ones.

Following the death of her mother at 56 to breast cancer, Jolie chose to have the genetic test to see if she had any BRCA mutations. With that history in mind and finding she did have BRCA mutations, Jolie's risk is above average. Predicted to have about an 87% chance of getting breast cancer and a 60% chance of getting ovarian cancer, Jolie opted to remove both breasts as a first step towards reducing her risk of breast cancer alone (she now has a less than 5% chance of developing breast cancer). Removing her ovaries is perhaps a more complex decision, a decision that requires a fine balance of timing. Removing the ovaries in a pre-menopausal woman, a surgery known as an oophorectomy, will push the woman into early menopause, which comes with several adverse side effects such as osteoporosis and a general decline in well being. This decision can have a profound effect on the health of the woman. As such timing, usually advised at around age 40 so that having children is not compromised, has to be carefully considered for high-risk individuals. And that is not even the full extent of BRCA mutations and cancer. This traumatic surgery will not reduce the risk of peritoneal, pancreatic cancer or melanoma; all are cancers that can develop with alterations found in these two genes.

But what are these malevolent mutations and how common are they?

BRCA mutations are errors found in the BRCA1 and BRCA2 genes. These genes, which stand for breast cancer susceptibility gene 1 and 2, produce proteins that help repair DNA. Specifically, they can mend breaks in the double helix caused by everyday stresses so that cells avoid the genetic damage that can lead to cancer. They are therefore also known as tumor suppressor genes because, when functioning as they should, they are able to maintain a happy DNA state within our cells.

Mutations in either of these genes are uncommon. And not all breast and ovarian cancers are due to mutations in these genes. Only around 5% of breast cancers arise from BRCA mutations and between 10-15% of ovarian cancers carry mutations in one of these genes. Furthermore, not all BRCA mutations are classed as high-risk.

In fact, there are many ways that genes can misfire. Mutations, which can be inherited or result from external factors such as UV or chemical damage, can mean that the gene product (in this case proteins that control the stability of our genetic material) will no longer function effectively. These mutations can come in many forms: a single mutation in one of the four DNA building blocks, a deletion of part of the gene, or perhaps rearrangements within the gene. However, not all of these errors will lead to a faulty gene product, and they can vary in their severity.

All medical decisions are acutely personal. At-risk individuals should always receive advice and make decisions about whether genetic testing, screening, and prevention strategies such as prophylactic surgeries and chemoprevention are necessary, taking into account other risk factors involved and also dealing with the emotional associations that come part and parcel with the "C word."