Hysterectomies may be advisable for women at high risk of uterine cancer

For years, women with BRCA genetic mutations have been advised by doctors to consider having their breasts, ovaries and Fallopian tubes removed to reduce their risk of developing breast and ovarian cancer.

Now, results from a new study may cause some of those to consider having hysterectomies to prevent as well.

"I do think this study will change behavior," said Dr. Matt McDonald, physician leader of Novant Health Cancer Care in Greater Charlotte. "With this information...I think a lot of women are going to say, 'Take my uterus out.'"

The study, which followed more than 1,000 women in 10 U.S. medical centers, found that women with mutations of the BRCA-1 gene are at high risk of developing an aggressive form of uterine cancer. Previous smaller studies had identified a link, but the evidence wasn't considered strong enough to change the way doctors practice.

"This is the study that has been needed," said Dr. Noah Kauff, a Duke University researcher and lead author of the study, published online in JAMA Oncology last week.

Until four months ago, Kauff worked at Memorial Sloan Kettering Cancer Center in New York, where his team published the first study, in 2002, which showed that removal of ovaries and Fallopian tubes in premenopausal women with BRCA mutations reduced the risk of breast and .

At the time, he said, researchers believed there wasn't a connection between BRCA and uterine cancer. But anecdotal stories and a 2013 New York Times report led them to question that conclusion. The Times story was about a women who had tested positive for the BRCA gene mutation and had her ovaries removed but opted not to have a hysterectomy to remove her uterus. Then five years later, she was diagnosed with advanced uterine cancer.

"Patients had been asking about this throughout my career," Kauff said. "Media reports caused us to re-look at this."

INCIDENCE OF AGGRESSIVE CANCER SIGNIFICANT

Kauff's team at Sloan Kettering subsequently published a 2014 study confirming that women with the BRCA-1 mutation had a higher risk of uterine cancer. It also found that the uterine cancer they developed was deadly.

Generally, uterine cancer is diagnosed early and can be cured with surgery alone, Kauff said. The five-year survival rate is 80 to 90 percent. But the Sloan Kettering study found uterine cancers in women with BRCA-1 mutations were of an aggressive type, called "serous" cancers. They account for only 10 percent of uterine cancer, but 40 percent of all uterine cancer deaths, Kauff said.

A larger study was needed to determine if the connection was significant enough to affect medical practice. So Kauff worked with researchers at nine other U.S. and United Kingdom centers to follow 1,083 women for about five years.

In the largest study so far, four of about 600 women with BRCA-1 mutations developed the aggressive uterine cancer. And while that doesn't seem like a lot, Kauff said the result was unexpected and significant.

"If you followed these 600 women for 25 years, you would have expected only one of these cancers," he said. "When in just five years, we saw four of them, that definitely raised flags."

Although Kauff wouldn't say whether women should have preventive hysterectomies, he did say in an interview that the new data is strong enough to prompt doctors to discuss the potential risk of aggressive uterine cancer with patients who have the BRCA-1 mutation.

'GOING TO CHANGE BEHAVIOR'

Novant Health's McDonald said he and other oncologists have "struggled with what to tell patients" about whether to keep their uteruses. "I would say, 'We really don't know what the right answer is right now.' I would really leave it up to the patient."

The latest study is "s going to change behavior a lot," he said.

Most surgery to remove ovaries and Fallopian tubes is done laparoscopically in 20 to 25 minutes, he said. "It's an outpatient operation. You wake up, go home and you're pretty much back to normal activities within days."

Hysterectomies can also be done laparoscopically, and that would add about 15 to 20 minutes. Recovery might be a week longer, but the risk of complications wouldn't be much different.

Both Kauff and McDonald said the study doesn't give clear direction for women who've already had preventive surgery to remove ovaries and Fallopian tubes and are considering hysterectomies. Second surgeries would bring additional cost and risks of complications.

The decision also remains difficult for women of child-bearing age who are still planning to become pregnant.

"That's what makes it a little tougher for me to make my decision," said Krystle Goverick, 34, a Pennsylvania volunteer for a national advocacy group. She isn't married and hasn't yet had children.

In 2014, more than 10 years after her mother died of breast cancer, Goverick learned she had the BRCA-1 mutation. She's already had a double mastectomy to decrease her risk of breast cancer, and in the next five years, she plans to have another operation to remove her ovaries and Fallopian tubes. Now, she's glad for the new data that will help her decide whether to have a hysterectomy as well.

"I'm so happy Dr. Kauff and others are taking the time to do this research," Goverick said. "It's really helping us make our own medically informed decisions."


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Women with BRCA1 gene mutation at higher risk of deadly uterine cancer

Journal information: JAMA Oncology

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