BRCA1 or BRCA2 gene mutations need not be fatal anymore. Preemptive removal of breasts or ovaries in women with the two common breast cancer genes can sharply reduce the risk of contracting cancer and dying, it has been shown.
Women who have either of the two BRCA genes have a lifetime risk of 56% to 84% of developing breast cancer. Women with the BRCA1 gene also have a 36% to 63% risk of ovarian cancer, and those with BRCA2 have a 10% to 27% risk.
But the removal of the ovaries and ovarian tubes in women can almost completely eliminate the risk of ovarian cancer and reduce the risk of breast cancer by about two-thirds, US researchers say. Removal of breasts can reduce the risk of breast cancer by as much as 85%. Either procedure reduces the risk of dying by at least two-thirds.
AdvertisementSuch prophylactic surgeries are believed to reduce the risk of cancer, but the new study, reported Tuesday in the Journal of the American Medical Association, is the first to show conclusively a survival benefit. It is also the largest such investigation to date and the first to differentiate the benefits based on which gene a woman has and whether or not she has already had cancer.
In the study, a team headed by Drs. Timothy R. Rebbeck and Susan M. Domchek of the University of Pennsylvania School of Medicine studied 2,482 women who had been diagnosed as BRCA carriers between 1974 and 2008. About 10% chose to have mastectomies and about 40% salpingo-oophorectomies, although there was some overlap between the two groups. More than half had neither procedure.
The most impressive results involved ovary removal. About 1% of women who had them removed were later diagnosed with ovarian cancer — mostly in tissue that surgeons had missed — compared with 6% of those who did not undergo surgery. Eleven percent of those who had their ovaries removed were diagnosed with breast cancer, compared with 19% of those who had no surgery. Three percent died of all causes, compared with 10% of those who had no surgery.
The main thing the study shows, Rebbeck said, is that "if you are a woman in this situation, there is something you can do to reduce your risk of dying from cancer."The study shows the benefits of genetic tests that give women with a family history of cancer the chance to take steps to increase their chances of survival, they said.
"This is the first study to prove women survive longer with these preventive surgeries and shows the importance of genetic testing when there is a family history of early breast or ovarian cancer," Dr. Virginia Kaklamani of Northwestern University in Chicago wrote in a commentary.
The study has been published in the Journal of the American Medical Association.
"We already knew intuitively that removing breasts reduces the risk of breast cancer, but this is the first paper that actually shows it contributes to a survival benefit," said Dr. Jane Kakkis, surgical director at MemorialCare Breast Center at Orange Coast Memorial Medical Center in Fountain Valley, who was not involved in the study. "That's a big difference in terms of helping patients make a difficult decision."
Prophylactic mastectomies sharply reduce the risk of breast cancer by surgically removing the bulk of tissue in which such tumors arise. Prophylactic removal of the ovaries and tubes, a procedure called salpingo-oophorectomy, not only nearly eliminates the risk of ovarian cancer by removing virtually all of the tissue in which it can arise, but also reduces the risk of breast cancer by sharply reducing the production of estrogen, which fuels the growth of breast tumors.
Most physicians now recommend that breast removal be considered anytime after the presence of the genes has been diagnosed. For patients who reject mastectomies for aesthetic or sexual reasons, the alternative is more intensive screening, with a mammogram or an MRI every six months. That is especially important for carriers of the BRCA1 gene, which is associated with a more aggressive, fast-growing form of breast cancer.
The vast majority of physicians recommend salpingo-oophorectomies for BRCA carriers once they are done having children, because there is simply no good alternative.
"That is the single most important intervention that we can do," said Dr. Jeffrey Weitzel of the City of Hope Medical Center in Duarte, who participated in the study.
Kakkis said that the greatest risk with the procedure is surgically induced menopause, but that studies have shown that even when hormone replacement therapy is used, the risk of cancer is still reduced by at least half.
Dr. Sandhya Pruthi, a breast cancer expert at the Mayo Clinic in Rochester, Minnesota, who counsels women with BRCA mutations, told Reuters the study added more evidence that the surgery could help save lives, but the choice was never easy.
"It's not cookie-cutter medicine," Pruthi, who was not involved in the study, said in a telephone interview.
She said women need to come to terms with the psychological issues involved in having their breasts removed, and younger women who have their ovaries removed must contend with early menopause symptoms.
"It's not a decision made on a single visit," she said.
According to the American Cancer Society and the International Agency for Research on Cancer, 1.3 million new breast cancer cases are diagnosed around the world every year and it kills 465,000 women annually, making it the leading global cancer killer of women.
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