Angelina Jolie’s Preemptive Strike Against Cancer

Angelina Jolie is back in the news, but not to promote a new film. Rather, she is promoting a personal decision to remove parts of her body before they turn cancerous. Two years ago, she underwent a double mastectomy to avoid the potential of developing breast cancer. This week, her sequel to this surgery was to have her ovaries and fallopian tubes removed. She wrote about this experience on March 24 in the New York Times.

On the surface, this may seem like an overly aggressive tactic to skirt cancer. However, Jolie’s family history is replete with tragic cancer deaths and she herself is a carrier of a mutant BRCA1 gene – more on that momentarily. Considered together, these attributes put Jolie in a high-risk category for cancer, so she elected to remove the time bomb from her system. Several doctors have applauded her decision given the circumstances. Jolie’s willingness to share her stories has created such an increase in awareness of genetic testing for disease that people call it the “Angelina Effect”.

Cancer…don’t mess with Angelina.

As discussed recently on THE ‘SCOPE, cancer is like a cellular rebellion and there is evidence that the cause of that rebellion is largely bad luck. In some cases, all it takes is one bad gene to incite the riot and in Jolie’s case it is BRCA1, which stands for BReast CAncer 1. BRCA1 is a key “biomarker” for cancer, meaning that the sequence of this gene can be an indicator for the likelihood that the cell housing it could go rogue and cause cancer one day. According to one study, women possessing a mutation in BRCA1 have a cumulative lifetime risk of 50%–85% of developing breast cancer and up to 60% of developing ovarian cancer. 

Looking at the diagram above, you don’t need to be a scientist to realize that BRCA1 is a cellular multitasker - best known for its tumor suppressive ability. A mutation in this important gene is likely to screw up a lot of things in the cell, potentially giving the green light for cancer to develop.

BRCA1 is a protein linked to many diverse cellular functions, some of which involve cell growth and the repair of damaged DNA. A mutation in the gene encoding BRCA1 can compromise the activities of the corresponding protein, wreaking havoc in the cell and potentially causing it to start replicating uncontrollably. So BRCA1 is a hero of sorts, a police officer that keeps cells in line. But if the officer is wounded, the cell has a ripe opportunity to rebel and take over the body in the form of cancer.

Angelina’s character Lara Croft can’t wait to get into tombs, but Angelina is doing all she can to delay entry into her own.

Removal of otherwise healthy organs that might go cancerous is not a trivial decision. First of all, biomarkers are informative but not a guarantee that disease is inevitable. Second, no surgery is without risk. Third, in Jolie’s case, her latest surgery will prompt early menopause and eliminate her ability to have more children. Fourth, while prophylactic surgery greatly reduces the risk of cancer, a small chance remains it could still develop. Finally, there are other less invasive treatment and monitoring options for individuals carrying a BRCA1 mutation or other risk factor associated with cancer. Consultation with a physician and oncologist is essential in order to weigh these risks against the results of genetic testing.

A preemptive strike against cancer by removing the suspect organ is not always a good strategy – consider brain tumors, for example!

 

Contributed by:  Bill Sullivan

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James, C., Quinn, J., Mullan, P., Johnston, P., & Harkin, D. (2007). BRCA1, a Potential Predictive Biomarker in the Treatment of Breast Cancer The Oncologist, 12 (2), 142-150 DOI: 10.1634/theoncologist.12-2-142

King, M. (2003). Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2 Science, 302 (5645), 643-646 DOI: 10.1126/science.1088759