Breast Cancer Genes at Work

Why a Patient Needs to Know their BRCA Status

While I’m sure most everyone knows that our DNA makes up genes that control how our bodies work, I’m guessing most people couldn’t name many of those genes. But thanks to Angelina Jolie, if anyone is going to remember a gene’s name, it’s probably BRCA. Mary Claire King and her team worked on isolating a gene responsible for hereditary breast cancers in the early 1990s, and in 1994, its exact location on chromosome 17 was identified by a team at Myriad Genetics. By the time I was in graduate school in the early 2000’s, I remember a lot of discussion about testing women at high risk for breast and ovarian cancer for mutations in the BRCA1 and BRCA2 genes. While the average woman has a 12% chance of developing breast cancer in her lifetime, the risk of developing breast cancer in a woman with a BRCA mutation approaches eighty percent.

Though a BRCA mutation only occurs in about 5% of all breast cancers, the chance of developing a cancer is so high in people with a mutation that individuals at high risk are often asked to consider this testing. In graduate school, I took a class with a genetic counselor discussing BRCA testing and learned that reputable institutions at the time suggested that no one should undergo BRCA testing without extensive genetic counseling because of the ramifications of a positive result (positive for a mutation, which is, of course, not a good thing). Even though HIPPA’s Privacy Rule had already been passed in 1996 making it illegal for a doctor, insurer, or testing company to release a patient’s results to a third party without their consent, many still feared the impact a positive result could have on their employment or their ability to get or keep health insurance. This fear was so prevalent that many in the scientific and medical communities worried patients would forgo testing that could impact their clinical care or would resist participating in genetic based research, and so the Genetic Nondiscrimination Act of 2008 was passed, prohibiting discrimination in the workplace and by insurers based on results of any genetic analyses.

By the time I was diagnosed with breast cancer in 2012, since I was young and diagnosed with triple negative breast cancer (both seen more often in patients with a BRCA mutation), I was instructed to spit into a tube for BRCA tests without even a mention about the existence of genetic counseling. I remember being surprised at how lax the requirements for genetic counseling had become, but knowing that it was information that I wanted, I dutifully swished the mouthwash and filled the tube. Because I fit into all the right categories, the test was technically “covered” by my insurance. But it’s an expensive test, so I had to give the company additional authorization a few days later because my out of pocket expense was still going to be significant. I was left to ponder the consequences from a more analytical standpoint. Was this information going to be worth it? After all, I already knew I had cancer.

Obviously, there is a benefit from knowing that you have a BRCA mutation before you develop cancer. It gives you the chance to be proactive. A woman can choose to be screened more frequently, or she can take the more extreme measure of prophylactic surgery. The removal of healthy breasts and ovaries is not a decision to be taken lightly, but many women, especially those who have watched mothers and other close relatives die of cancer, consider the benefit to be great enough to make the sacrifice. So, if I had discovered I had a BRCA mutation, I would have been given the option of removing my ovaries– to have a prophylactic oophorectomy. But really, the biggest driver for my decision at the time was my beautiful eight year old daughter. My heart broke not only as I thought I may bear a gene mutation that could cause me to die as a young mother, but as I realized that my daughter might face the same fate. In fact, a mutation for me meant a lot of testing for my entire family, as not only my kids, but my parents and brother would also face an increased risk of multiple cancers if they too possessed a mutation. And so would my brother’s baby girl, who was due to be born any day. That’s a lot to carry around as a newly diagnosed cancer patient. Knowing that the likelihood I had a mutation was pretty low, I just wanted that weight off my shoulders. Given the low prevalence of BRCA mutations, I wasn’t surprised to receive a negative (no mutations, yay!) result, but it was certainly a relief.

But what if those situations hadn’t applied? Let’s say for some unrelated medical reason I’d already had my ovaries removed and I was adopted and didn’t have any kids. No extra surgeries that I might need and no blood relatives to worry about. While the legislative protections in place keep me from worrying about employment and insurance ramifications, would I still want to shell out the money to know my BRCA status? My answer may have been different only  ten years ago, but today I would definitely want to know. Two years ago, olaparib (Lynparza by Astra Zeneca) was officially approved by the FDA for the treatment of ovarian cancer in patients with a BRCA mutation. Because of the mechanism by which olaparib attacks cancer cells (inhibiting the PARP enzyme), it is especially effective in patients with a BRCA mutation, and olaparib and other PARP inhibitors are currently in trials for breast cancer patients bearing a BRCA mutation. This means that a BRCA mutation is now informative in making treatment decisions– it makes a patient eligible to take a drug that otherwise would not be offered that could have significant clinical benefit. If a patient knows their BRCA status, that will help them get the right drug for their tumor, and to me, that makes all the difference in the world. The right drug to the right patient at the right time. That’s precision medicine.

For a more extensive review of the biology and history of BRCA1 and BRCA2, check out Cure Forward’s BRCA Gene Story.

Jamie Holloway Precision Medicine Advocate

Jamie Holloway

Jamie Holloway is a both a scientist and a survivor, earning her PhD in tumor biology from Georgetown University a few years before her own breast cancer diagnosis. Now living with no evidence of disease after treatment for early stage triple negative breast cancer, she bridges the gap between scientists and researchers as a Precision Medicine Advocate for Cure Forward and as the Patient Advocate for the Metastatic Breast Cancer Project at the Broad Institute. She works with researchers as part of the Georgetown Breast Cancer Advocates and writes about her personal experience with cancer on her blog, Run Lipstick Chemo, and as a contributor to the Cure Magazine community.