Joe Scholten's sister had already beaten breast cancer and was battling ovarian cancer when she tested positive for a genetic mutation linked to both. He responded by doing something unusual: He got tested, too.
That's how the District of Columbia resident discovered that he also carried the defective BRCA gene. He quickly told his brothers, other relatives and, hardest of all, his daughter. "Getting tested was a no-brainer," he said, wondering what steps his sister would have taken if she had learned early on about her own genetic risk. She was 54 when the ovarian cancer killed her. He realizes now that not knowing your medical pedigree is "clearly a danger."
Yet Scholten's action makes him an outlier. Many women are acutely aware of the stark dangers posed by mutations in the BRCA1 and BRCA2 genes — the kind that prompted actress Angelina Jolie to have her breasts and ovaries removed pre-emptively. Few men, however, know that the same genetic defects can have deadly consequences for them as well as their children.
New research could prompt a major rethinking. BRCA mutations were already linked to prostate cancer, and a growing body of studies suggests they might play an even bigger role than early findings indicated. Men with these mutations are more likely than noncarriers to contract aggressive, lethal prostate cancer, to be diagnosed at a more advanced stage and to ultimately die of the disease, researchers say. Just last week, a new analysis showed that men with BRCA2 mutations had a higher rate of late-stage prostate cancer at the time of diagnosis and worse outcomes.
"We are only just beginning to truly understand how these genes could impact a man's risk," said Brian Helfand, a urologic oncologist with NorthShore University HealthSystem in Evanston, Ill.
The latest studies suggest that a man's BRCA status can be an important piece of information, especially at a time when many doctors are taking a less aggressive stance in screening and treating prostate cancer.
The two genes produce proteins that help repair damaged DNA, and alterations in either diminish the body's defense against cancer. Besides being linked to breast, ovarian and prostate cancers, BRCA defects have been implicated in melanoma and pancreatic cancer. If a parent has the mutation, a child has a 50 percent chance of inheriting it.
Although many people who have these mutations won't ever get cancer, the risks are still much higher. They differ by individual cases, race and gender.
An estimated 12 percent of women will develop breast cancer during their lifetimes, according to the National Cancer Institute. That proportion rises to as high as 65 percent of women who inherit a BRCA1 mutation and about 45 percent for those with a BRCA2 defect. Almost 40 percent of women with a BRCA1 mutation and up to 17 percent with a BRCA2 defect will get ovarian cancer.
Men's risk of getting breast cancer, generally one in 1,000, rises to about 7 percent for BRCA2 mutation carriers. That's "significantly elevated," said Marc Schwartz, co-director of the cancer prevention and control program at the Georgetown Lombardi Comprehensive Cancer Center. A BRCA1 mutation also appears to increase the risk, but it's not clear by how much.
As for prostate cancer, the analysis presented last week at an American Urological Association meeting found that 17 percent of patients with BRCA2 mutations already had advanced disease, four times the rate of patients without the mutation. In a study on African American men, researchers at the Walter Reed National Military Medical Center examined more than 850 archived blood samples and found that blacks were more likely than whites to have a BRCA1 or BRCA2 mutation, as well as more aggressive disease.
"The problem is, everyone associates this with women and their cancers," said Bruce Montgomery, an oncologist at the Seattle Cancer Care Alliance/University of Washington Medical Center. "In men's minds, BRCA is about breast cancer, so they don't see it as relevant."
Bill Rotter, 63, of Mequon, Wis., wishes he had known earlier about his BRCA2 mutation. He probably wouldn't have ignored the pea-sized lump he discovered next to his right nipple in late 2013. When he finally had a mammogram, ultrasound and then biopsy, invasive ductal carcinoma was found, making him one of about 2,200 American men diagnosed with breast cancer each year. About 400 die of the disease annually.
Rotter had a mastectomy on his right side and a second surgery a few weeks later to remove 13 lymph nodes because the cancer had appeared in a "sentinel" node. Chemotherapy and radiation followed. He learned of his genetic mutation in between the two surgeries and wonders if earlier action could have prevented the disease from spreading.
In retrospect, he said, the finding shouldn't have been a surprise: His father died of prostate cancer at 64, and two of his father's brothers also died of the disease. A male first cousin he had never met died of breast cancer in his 30s. Plus, his family's Ashkenazi Jewish heritage increases the chance of being a mutation carrier by tenfold.
The father of two sons is now what Boston College sociologist Sharlene Hesse-Biber calls a "BRCA warrior," one of a small group of men determined to alert others to the dangers of inherited genetic defects. "My passion is to create awareness about the genetic component of cancer," said Rotter, who writes occasional blog posts for Ambry Genetics, a company that offers testing. "It is amazing how many people, even in the field of medicine, have no clue."
BRCA mutations have testing and treatment implications for men, who, for starters, should be screened for prostate cancer starting at age 40, according to Theodora Ross, director of the cancer genetics program at the University of Texas Southwestern Medical Center.
In addition, drugs called PARP inhibitors, which have been shown to benefit some ovarian cancer patients with BRCA mutations, may be of use for prostate cancer patients with the gene defects.
But if men embrace more genetic testing, they'll inevitably face the kind of questions women have been dealing with for years. Not all families want to discuss their health risks, as Vincent Moltisanti of Staten Island realized when his breast cancer was diagnosed in 2005.
He put together a family medical history and underwent genetic counseling. "In Italian families, no one gives out information about their health; it's on a need-to-know basis," said Moltisanti, who is now 68. "You have to kind of guess what your great aunts and uncles had and what caused their demise."
When testing showed he had a BRCA mutation, his daughter, Jaime, was tested and told she was positive as well. She planned to have her breasts and ovaries removed at some point but died of lung cancer in 2014.
Moltisanti urged his two older brothers to take action. Neither was interested. "You'd think they would want to know," the retired longshoreman said, adding that he worries not only about both of them but about his nieces and nephews and their children.
Scholten understands the risks of family secrets. His sister, a lawyer who lived in Alabama, contracted breast cancer in the early 2000s but kept it to herself because their mother had dementia, and she didn't want to upset her. She didn't know that a male cousin had died of breast cancer.
If her doctors had known about their cousin, maybe they would have ordered testing much earlier, Scholten said. As it happened, his sister didn't undergo testing until after her ovarian cancer was diagnosed.
"The dots," he said, "didn't get connected."