Unlocking the secrets of our genes, including the mutations that predict disease, puts people in a precarious position, particularly when there are no easy options. Many women who carry the heavy burden of knowing they are at high risk for breast or ovarian cancer — a result of genetic testing for the BRCA1 and BRCA2 gene mutations — are increasingly opting for surgery to reduce their risk.
It's a radical choice, but indicative of fear that comes with knowing one's likely genetic fate. News of this growing trend comes from a just-released study at the same time last week that Nobel prize-winning James Watson — who discovered the double helix of DNA — wrote a column in the New York Times criticizing the National Cancer Institute (Bethesda, Maryland) and calling for the agency to "... radically speed up the pace at which anticancer drugs are developed and clinically tested." (To Fight Cancer, Know the Enemy, Aug. 6, 2009.)
"I personally feel surgery is too radical," lead researcher D. Gareth Evans, MD, a consultant in clinical genetics at the Genesis Prevention Center, University Hospital of South Manchester NHS Trust (Manchester, UK) told Medical Device Daily. Evans and colleagues assessed the increase in risk-reduction surgery among women in a study just published in Cancer Epidemiology, Biomarkers & Prevention.
"Hopefully we'll have a treatment in the not-to-distant future for these women with an 80% risk of developing cancer," he said. "But surgery is an inevitable choice if they have no other viable alternative. It's not such a radical option because it's more radical to face chemotherapy and surgery to remove cancer."
Surgery to head off chances of developing breast or ovarian cancer means bilateral mastectomies and bilateral salpingo-oophorectomy (removal of ovaries).
Evans and his colleagues have wondered about women's choices when faced with genetic testing results that reveal their mutations.
"Over the last 10 years, we've been looking at the idea of what the uptake of preventive surgery is likely to be," he said. "We've been keeping a weathered eye on the interest and demand and what the uptake is. We're in a position now to say we followed all these women long enough and we can make a definitive statement that it confirmed what we suspected. By and large, these decisions about surgery are driven by risk."
But women don't jump into the surgery easily. In fact many take years to decide.
"What surprised me the most was that the real delay in uptake of surgery is seven to 12 years after original genetic assessment," Evans said. "Clearly the decision was not driven by the initial genetic assessment, but by events that occurred after that. Subsequent family events pushed them into it such as more cancer in the family or they themselves had a biopsy of benign disease which made them fearful of what might happen in the future."
The rate of surgeries was measured among 211 women who were BRCA1 or BRCA2 mutation carriers. Additionally, more than 3,500 women at greater than 25% lifetime risk of breast cancer without mutations also had a documented increase in risk-reduction surgery.
The study revealed that women who had a biopsy after undergoing risk evaluation were twice as likely to choose a risk-reducing mastectomy. Almost half, 45%, of the women who were mutation carriers underwent bilateral risk-reducing mastectomy and 45% had bilateral risk-reducing salpingo-oophorectomy.
Bilateral risk-reducing salpingo-oophorectomy was more common in women who were BRCA1 gene carriers: 52% had the surgery compared with 28% of the women who were BRCA2 gene carriers.
Evans noted a few other trends from the study. He found that women over the age of 50 are less likely to have mastectomies. Almost half of the women thought that they had already lived long enough to think they would get beyond the cancer risk.
And women who had already been through menopause found it less important to have their ovaries removed, even if they carried the genetic mutation.
For the women who opt for surgery, "These are emotional decisions based on what they've experienced in their families," he said, adding that a woman who lost her mother to breast cancer while she was still a teenager was more likely to have a preventive bilateral mastectomy."
Evans pointed out that women who opt for mastectomies may not necessarily be facing such a radical choice if well-done reconstruction is an immediate option. Given that option, he said that half of all women will choose surgery over time.
"If you see some of the results that can be produced by very good surgeons, then it doesn't seem like such a radical option," Evan said. "They can pass the shower test, meaning they can go into a changing room in a sports club and no one would see anything untoward about their appearance. It's that balance between surgical risk reduction and cosmesis. If it's not that mutilating, then it may not be such a radical option."
Still, Evans thinks there should be a better way to prevent cancer.
"It's very expensive to develop cancer cures," he said. "It's even more expensive to develop preventive cures. In Europe, tamoxifen isn't even licensed as a preventive because there's not money in it."
"Health agencies in Europe and the U.S. have to be more proactive in making this research happen and it may mean going into partnership with drug companies," he said.
In Watson's NYT column he called for President Obama to appoint strong new leadership, saying the NCI " ... has become a largely rudderless ship in dire need of a bold captain who will settle only for total victory."
"I expect that my views will provoke rebuttals from prominent scientists who feel that it's not yet the time to go all out against cancer, and that until victory is more certain we should not further tap our limited coffers for more big-cancer money. While they are right that victory will not come from money alone, neither will it come from biding our time," Watson wrote.
Lynn Yoffee, 770-361-4789; email@example.com