Clinicians and the public need to be aware that being positive for BRCA mutations has consequences for men and their families, too.
Linda Penwarden, MN, RN, AOCN
“Linda, I’m going to die!” The strained voice was that of my former husband Michael in a message left on my work phone. I had not expected to hear from him during the day since he was undergoing a prostatectomy; my son and I planned to visit him in the hospital after work. I certainly didn’t expect to hear those words.
It was 2008, and weeks earlier Michael’s prostate biopsy finally showed cancer. I say finally, as it was one of many biopsies performed in the face of a rising PSA. The surgery was to be “routine,” and a good surgical outcome was anticipated. He was likely to be one of those men that did well following surgery and perhaps radiation. Unfortunately, the prostatectomy was never completed.
At the hospital that evening, Michael relayed the surgeon’s message: extensive cancer, stage IV disease, and a prognosis of 2 years. What? This was shocking news, and a strong sense of failure followed for not having caught this earlier.
As an oncology nurse for more than 20 years, I knew the majority of men with early prostate cancer did very well. My own father was a classic example, having been diagnosed and treated with leuprolide for the last 3 years with hardly a break in his stride.
Could It Be BRCA?
Michael proceeded with the usual next steps: radiation and androgen ablation treatment. His PSA never went to zero. Within 1-2 months following completion of radiation, his PSA began to rise, suggesting disease progression. It never seemed to really stop much. The addition of bicalutamide had little effect. Referral to medical oncology followed.
In the back of my mind, I had a nagging thought and eventually mentioned it to Michael. Could he have a genetic mutation, namely BRCA2, which was playing a role in the aggressiveness of this cancer?
A few years prior, in 2003, we were contacted by an agency that assists adopted people in finding their biological family. I received a phone call from a woman asking unusual questions about the whereabouts of Michael’s parents (both deceased). The memory of suspicions by one of Michael’s sisters came to mind: she recalled as a child that their mother had gone to the hospital pregnant and returned without a baby. Was that baby given up for adoption?
The answer, as it turned out, was yes, and a new sister, Ann, joined the group of five siblings. Ann had grown up in a very loving and caring family, yet her drive to find her biological family came from an unfortunate discovery.
At age 40, Ann was diagnosed with breast cancer. Having been adopted, she had no family history with which to evaluate hereditary risk. Wisely, her surgeon recommended genetic testing and the results—positive for the BRCA2 mutation—were the driving force behind the search for her biological family. In Ann’s words, “A bolt of energy shot me out of my chair and I knew exactly what I needed to do. It was no longer just about me or curiosity.”
In our first meeting with the medical oncologist, I explained the situation and asked if it was reasonable to test Michael. Having a copy of Ann’s results, the testing would be specifically for that mutation. The oncologist agreed, and Michael subsequently underwent testing. We were aware that the testing would not benefit Michael, but the implications for our 11-year-old son were clear.
The results came back: “positive for a deleterious mutation” of BRCA2. We were both devastated knowing that our son had a 50/50 chance of inheriting this mutation. We were also informed that Michael’s prostate cancer was likely more aggressive as a result of this mutation. That was certainly clear by this point.
Multiple treatments followed: ketoconazole, docetaxel, and abiraterone. These are all therapies used to treat progressive disease when others have failed. Palliative radiation was used to treat bone metastases, which seemed to crop up every few weeks or so. Sadly, Michael succumbed to his prostate cancer in September 2011.
I placed the results of his genetic testing within a safe along with my will. There were instructions for my sister to divulge this information to my son if I hadn’t already done so, should something happen to me. I had numerous conversations with the genetic counselor about how and when to inform him.
Hearing BRCA2 for the Second Time
For men, it’s recommended that testing be offered in their mid-20s, since early screening wouldn’t be necessary until age 35. However, in 2014, at age 17, my son was headed off to college, and it seemed reasonable to begin discussing this before he gained his independence.
My son felt he could have been told of this possible risk sooner. He didn’t hesitate. “Of course I want to be tested.” I was prepared to support any decision he made. It was reasonable to wait and decide later. With a full life ahead of him I felt there was such a burden in knowing, and yet there is power in knowledge.
I can’t explain why I knew what the results would be, and as I sat listening to the genetic counselor tell him that he indeed tested positive for the BRCA2 mutation, I felt a déjà vu hearing this for a second time.
My son asked very intelligent questions about level of risk, and listened to her recommendations. For men, there seems to be much less that they can actively do to mitigate this elevated threat. Cancers related to the BRCA2 mutation in men include prostate, pancreatic, and male breast cancers, as well as melanoma.
The public’s awareness of the BRCA mutations came alive with Angelina Jolie’s revelation in 2013 of her own BRCA1 positivity. The “Angelina Jolie Effect” has resulted in greatly increased screening for this mutation in women. But where are the men? Are there an equivalent number of men and women carrying these mutations? Isn’t the impact on them just as important? Risk of inheritance is 50/50 regardless of gender.
Consider the labeling of this mutation—BRCA—which stands for BReast Cancer; this can be misleading, even for women. The mutation elevates the risk for ovarian cancer as well. Men are rarely recognized in the literature or public commentary when it comes to awareness and discussion about the influence of this unfortunate mutation.
Family History and Genetic Counseling
In addition to the effect this gene had on Michael and Ann, other family members have been impacted. Ann’s daughter Rachel tested positive for the mutated gene at age 19. She was advised to wait until her mid-20s to pursue “vigilant monitoring.” When her cousin was diagnosed with breast cancer, Rachel made contact with a high-risk breast clinic and underwent extensive genetic counseling, gathering current and evidence-based information about her options. Subsequently at age 25, she chose to have bilateral mastectomies and reconstruction to reduce her risk of breast cancer.
Mollie, Rachel’s cousin and another one of Michael’s nieces, was unfortunately diagnosed with breast cancer at age 27 in 2013. Mollie has completed surgery and adjuvant treatment for her breast cancer and is actively considering fertility treatment along with preimplantation genetic diagnosis (PGD). This procedure would allow for testing the embryos for the BRCA2 mutation and selecting those without the gene.
As for my son, he is now well informed about the importance of cancer prevention, being aware of his body, and reporting changes. He has followed most of these healthy habits for years, such as going to the gym, maintaining a healthy weight, and using sunscreen regularly. He may need to begin prostate cancer screening earlier than usual, but that is still years away. He is also aware of the implications for a family in the future.
With BRCA mutations we need to remember that men matter. Clinicians and the public need to be aware that being positive for BRCA mutations has consequences for men and their families, too. It’s time to start talking about—and including—men in these discussions.
Linda Penwarden, MN, RN, AOCN has been a nurse for more than 27 years and is an oncology clinical nurse specialist at Mountain States Tumor Institute in Boise, Idaho. More importantly Linda is a mom and family member in which cancer genetics have played a significant role in the lives of those mentioned and not mentioned in this article. Linda wants to get the word out to others affected by this genetic mutation.
Helping Patients to Understand Their Risk
The National Cancer Institute reports that from 5% to 10% of prostate cancer cases are believed to be primarily caused by high-risk inherited genetic factors or high-risk susceptibility genes. Although genetic testing for prostate cancer is not currently standard practice, research has shown that risk is elevated in men with mutations in BRCA1 and BRCA2, and on a smaller scale, in mismatch repair (MMR) genes.1 In particular, prostate cancer has been observed at higher rates in men who harbor the BRCA2 mutation.
A recent study by Mersch et al of approximately 1000 patients testing positive for a deleterious BRCA mutation, reported that individuals with a BRCA2 mutation had significantly higher numbers of cases than expected for pancreatic cancer in both men and women (Standard Incidence Ratio [SIR] = 2.17; CI 95%, 13.1-34.0; P < .001) and for prostate cancer in men (SIR = 4.9; 95% CI, 2.0-10.1; P = .002).2
The US Preventive Services Task Force (USPSTF) issued guidelines in May 2012 recommending against routine PSA screening. Research reported recently at the annual meeting of the American Urologic Association has demonstrated that the guideline has resulted in a decline in screening.3 The group Facing Our Risk of Hereditary Cancers Empowered (FORCE) notes that after concerns were raised about how this guideline would impact screening for men with BRCA mutations, USPSTF modified its guidelines to acknowledge that they do not apply to men with BRCA mutations. Experts recommend a PSA blood test and baseline digital rectal exam for all men with BRCA mutations, starting at age 40.4
The international IMPACT trial is looking at the issue of PSA screening in men with and without BRCA mutations, and early analysis suggests of benefit of PSA screening in men with BRCA mutations.4 The trial, which involves five US research sites, is expected to be completed in 2020 and is continuing to recruit participants.5
Oncology nurses have an important role to play in educating their patients about genetic risk for prostate cancer and directing them when appropriate to genetic counseling. A family history of cancer, particularly of the breast, ovary, and prostate, is known to be a major risk factor for developing prostate cancer. A man with a father or brother who had prostate cancer is twice as likely to develop the disease. The risk is higher for men with a brother or father with the disease and is much higher when several relatives are affected, especially if the relatives were diagnosed at a younger age.