Women who inherit either of two faulty BRCA genes are at much higher risk of developing breast and ovarian cancer than other women, and at younger ages. Actress Angelina Jolie generated headlines last year when she had her healthy breasts removed to reduce her cancer risk.
Monday's study is the largest yet to show the power of preventive ovarian surgery for those women. The surgery not only lowers their chances of getting either ovarian or breast cancer. The study estimated it also can reduce women's risk of death before age 70 by 77 per cent.
Ovarian cancer is particularly deadly, and there is no good way to detect it early like there is for breast cancer. So for years, doctors have advised BRCA carriers to have their ovaries removed between the ages of 35 and 40, or when women are finished having children.
The new study suggests the surgery, called an oophorectomy, should be timed differently for the different genes.
For women who carry the higher-risk BRCA1, the chance of already having ovarian cancer rose from 1.5 per cent at age 35 to 4 per cent at age 40, said lead researcher Dr. Steven Narod of the University of Toronto. After that, the risk jumped to 14 per cent by age 50.
In contrast, the researchers said carriers of the related BRCA2 gene could safely delay surgery into their 40s. The study found only one case in a woman younger than 50.
Ovarian surgery "is the cornerstone for cancer prevention," declared Narod, whose team published the research in the Journal of Clinical Oncology. "The typical woman with a BRCA1 mutation will benefit to a large extent from an oophorectomy at age 35, and we want to make that a pretty standard recommendation."
Future studies would have to verify the findings, and other specialists urged caution.
Waiting until age 40 for ovary removal, as many women with BRCA1 do today, makes a very small difference, stressed Dr. Claudine Isaacs, an oncologist and cancer risk specialist at Georgetown University's Lombardi Comprehensive Cancer Center, who wasn't involved in the new research.
The findings shouldn't frighten women into acting sooner if they're not ready, agreed Dr. Susan Domchek of the University of Pennsylvania's Basser Research Center for BRCA, who also wasn't involved in the study.
Many women have babies during their late 30s, and ovary removal sends women into early menopause that can increase their risk of bone-thinning osteoporosis or heart disease later on.
"Thirty-five isn't necessarily a magic number," Domchek said. "If you are talking to a woman who hasn't yet finished having her kids, it's a completely reasonable thing to discuss the low risk of ovarian cancer by age 40 in the context of the other decisions that she's making in her life."
But Domchek added: For BRCA1 carriers, "by age 40, I will be nagging you about this again."
About 1.4 per cent of women develop ovarian cancer at some point in life, but 39 per cent of BRCA1 carriers do, and between 11 per cent and 17 per cent of BRCA2 carriers, according to the National Cancer Institute. Likewise, 12 per cent of average women will develop breast cancer, but a BRCA mutation raises the risk four- to five-fold.
The new study included 5,787 BRCA carriers from Canada, the U.S. and parts of Europe. Researchers tracked their health for an average of 5 1/2 years, and found 186 who eventually developed either ovarian cancer or related fallopian tube or peritoneal cancer. Ovary removal reduced cancer risk by 80 per cent.
Interestingly, removing the ovaries can reduce the risk of breast cancer as well by affecting hormone levels in the body — and Narod found the surgery increased women's chances of survival even if they already had developed breast cancer.
Specialists say more than two-thirds of BRCA carriers undergo ovary removal at some point, compared with about a third who choose a preventive mastectomy. Insurance generally pays for the procedures.
Key to the ovary decision is having a doctor who knows how to treat the hot flashes and other menopause problems that can make women delay the surgery, said Georgetown genetic counsellor Beth Peshkin.
Lauren Dubin of Olney, Md., knows what a difficult choice it is. Her mother, aunt, sister and cousins all developed breast cancer, but Dubin didn't know ovarian cancer also was a risk until she underwent gene testing at age 40 and learned she carried BRCA1. Despite fear of early menopause, Dubin had her ovaries removed a few months later, managed the symptoms and is glad she did.
Later, doctors also discovered early-stage breast cancer, prompting Dubin to have both breasts removed as well. Her daughter, in her 20s, also has BRCA1, and Dubin, now 54, hopes scientists find better answers before she faces the ovary decision.
"There is something about that mark, that point in time that 40 represents that feels very different than 35," Dubin said. "This doesn't end with us. There's the next generation."