NEW YORK (Reuters Health) - Women with BRCA1 mutations may be at increased risk of aggressive uterine cancer, which should be considered when deciding whether to have concomitant hysterectomy during risk-reducing salpingo-oophorectomy (RRSO), according to a new study.
"Women with BRCA1 mutations have a small, but important risk of serous uterine cancer. It remains even after removal of the ovaries and fallopian tube," Dr. Noah D. Kauff of Duke University, Durham, North Carolina, told Reuters Health by phone.
"The reason this is important is while most uterine cancers are actually diagnosed at an early stage and are highly curable, in many cases with surgery alone, and are associated with five-year survivals approaching 80-90%, serous uterine cancer is much more aggressive and is associated with a five-year survival approaching 50%," he explained.
As reported June 30 in JAMA Oncology, Dr. Kauff and colleagues at nine U.S. medical centers have tracked 1,083 women with BRCA1, BRCA2, or both mutations who had RRSO without comcomitant hysterectomy between 1995 and 2011. They included follow-up data through October 14, 2014 in the current analysis.
The researchers compared the incidence of uterine corpus cancer in this cohort with expected rates per the Surveillance, Epidemiology, and End Results database.
The median age at hysterectomy was 45.6.
There were eight uterine cancers in the study cohort, versus an expected 4.3. Five of the uterine cancers were serous or serous-like; these occurred 7.9 to 12.9 years after RRSO. Of those five, four were associated with BRCA1+ and one was associated with BRCA2+.
Of 627 BRCA1+ women, five developed uterine cancer versus an expected 2.8. Of 453 BRCA2+ women, three developed uterine cancer versus an expected 1.9.
In molecular analysis of three available tumors, the researchers confirmed the loss of wild-type BRCA1 gene and/or protein expression.
The researchers estimated the risk of developing serous or serous-like uterine cancer through age 70 for a BRCA1+ woman who undergoes RRSO at age 45 to be 2.6% at a constant annual risk and 4.7% at a constant relative risk.
Even a 2.5% to 4.5% lifetime risk "is something we think is important for women to consider as they're discussing what is the best risk-reducing surgery in the setting of a BRCA1 mutation," said Dr. Kauff.
"Because we don't have screening for ovarian cancer, the current standard of care is to recommend that women preventively remove their ovaries and fallopian tubes after childbearing is complete once they enter the risk period for ovarian cancer," he said. "What's been an ongoing question is whether or not the uterus may be at risk as well."
"Our study is the first large prospective study to be able to break down the cancers by subtype. Although we saw about a doubling of uterine cancer risk overall we would've expected just over four uterine cancers to be diagnosed in this cohort during the study period, we saw eight," Dr. Kauff continued. "Of the serous uterine cancers, which generally only account for about 10% of uterine cancers, we saw five. What was different was when you look at how many of these would've been expected, in this cohort, during five years of follow-up we would've expected to see 0.34. Even if we followed these women three times longer, we would've expected to see one uterine cancer. This is a highly significant result."
Dr. Ronald D. Alvarez of the University of Alabama at Birmingham, who coauthored an accompanying editorial, told Reuters Health by email, "For those patients with a BRCA mutation, particularly BRCA1, the risk/benefit of doing hysterectomy at time of RRSO should be considered especially for women who might be in need of hormone replacement therapy."
He and his coauthors wrote in their commentary, "At the present time we would recommend that all women with a BRCA1/2 mutation undergoing RRSO should be made aware of the potential risks and benefits of a concurrent hysterectomy and of the limitations in the available studies on this issue prior to making an individualized decision."
The National Institutes of Health and a number of other organizations supported this research.
SOURCE: http://bit.ly/296JBTQ and http://bit.ly/29HmnpN
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