It sounded like science fiction as little as 10 years ago: doctors analyzing an individual’s genetic code, her personal history and her environment to figure out not just what’s making her sick, but also what medicine she’ll respond to best or what diseases might be hiding in her genes. It’s an approach known as precision medicine, and although it’s still in its early stages, it has come a long way in a relatively short amount of time. Headlines about Herceptin, a breast cancer drug that slows or even stops the growth of tumours with high levels of a protein called HER2, and Kymriah, a leukemia drug that uses a patient’s own cells to potentially cure her cancer, have given us a peek at what might be possible in the field — but the best may be yet to come, and precision medicine could have a big impact on women’s health.
“This is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle,” says India Hook-Barnard, director of research strategy and associate director of precision medicine at the University of California, San Francisco. Translation: Things are about to get personal.
You might think medicine is already precise. After all, when you go to the doctor, she’s likely to ask a lot of questions about your lifestyle, family history and, of course, symptoms. But those questions are aimed at diagnosis, not treatment.
“Historically, we have treated patients with a one-size-fits-all manner, which doesn’t work well for everyone,” says Cara Tannenbaum, professor in the Faculties of Medicine and Pharmacy at the Université de Montréal and scientific director of the Institute of Gender and Health at the Canadian Institutes of Health Research.
Tannenbaum is talking about treatment protocols, or “standards of care,” which are based on scientific research and lay out exactly what procedures or medicines a physician should recommend for every disease or condition. (If the first line of treatment doesn’t work, there are often agreed-upon second, third and fourth options too.) Issues of access aside, the standard of care is the same for each person. It doesn’t take into account the genetic mutations that could cause a particular type of cancer, environmental factors that might provoke those mutations or how someone’s diet might impact how medication is metabolized. Under the current model, each patient is getting care that’s been shown to help most people, most of the time — but it may not help that particular patient at all. These “trial-and-error approaches can have problems,” Tannenbaum says. “But approaching medical treatments in a bespoke manner will lead to a much better fit for most patients and, of course, better health outcomes.”
How it works
The key to precision medicine is information. “The goal is to collect, connect and analyze vast amounts of data from many patients and healthy individuals so we can learn what works — and doesn’t work — for people most like the patient and better tailor care for that individual,” explains Hook-Barnard. That means understanding a patient at the molecular level, including her genome and microbiome, plus monitoring behaviour (for example, how often does she exercise?) and environmental factors (how’s the air quality where she lives?).
Hook-Barnard uses Google Maps as an analogy: The app pulls in all sorts of information, from road maps to traffic delays to public transit routes, analyzes it all, then tells you the fastest way to get home. Precision medicine’s goal is to do something similar, linking all the diverse data types that are relevant to health.
Analyzing all that data via computer algorithms allows “clinicians, researchers and patients to work together to gather more precise information about the patient and compare their data with information from many other patients, to more quickly learn what treatment approaches are likely to be successful, and to accelerate research and discovery of new therapeutics,” she says.
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This is happening all over the place: Toronto’s Mount Sinai Hospital launched the Canadian Open Genetics Repository in 2013. A national database of genetic markers and mutations, it helps doctors access information about the genetic causes of disease. In 2015, former U.S. president Barack Obama approved funding for the Precision Medicine Initiative, a study that would see a million or more Americans share their health and genetic information with researchers. And worldwide, the Collaborative Oncological Gene-environment Study mapped more than 200,000 individual genetic sequences; the outcome of the four-year study was the discovery of 154 new genetic markers for breast, ovarian and prostate cancer.
Why women will benefit
Precision medicine has the potential to improve health care for everyone, but it may also help dismantle some of the ways health care is biased against women, says Deborah Money, executive vice dean of the University of British Columbia’s faculty of medicine. Women weren’t regularly included in clinical trials until the 1990s, and even now, trial participants skew male. And when it comes to treatment, doctors don’t always consider women’s physiology. “We’ve had a huge gender disparity in health research and interventions,” Money says, “and precision medicine allows us to leap beyond that more quickly than we might have.”
Tannenbaum agrees. “I’d say 80 to 90 percent of what happens in the doctor’s office is sex-neutral,” she explains. “We have the same guidelines for high blood pressure, colon cancer, diabetes. . . . Now, for some things, maybe that’s how it should be. But for the most part, we haven’t done the research to know that for sure.”
Tannenbaum believes that as more research is done, we will find differences. Women have biological systems and gene markers that are unique to their sex, much in the same way that a group of patients with a disease-causing genetic mutation have gene markers unique to that group. If women’s genetics can impact prevention strategies, diagnosis and treatment, it only makes sense to take them into account.
There are three areas where women could feel precision medicine’s impact the most: cardiovascular health, sexual and reproductive health, and breast cancer.
We’ve known for years that women experience cardiovascular disease (CVD) differently than men do — though women are still the minority in research trials. But research suggests that there are actually female-specific genetic causes for CVD, an umbrella term for the group of conditions that cause narrowed blood vessels that can lead to heart attack, angina or stroke. For example, one study shows women with a rare mutation to a rare gene called HFE are more likely to have a higher risk of developing CVD. (There was no association between this genetic mutation and risk for men.) This type of sex-specific research is especially important because CVD is the number-one cause of death for Canadian women over the age of 55 and kills seven times as many people as breast cancer does.
Louise Pilote, professor of medicine at McGill University, is excited by the implications of including more women in clinical studies, a relatively recent change. Studying women has already yielded a wealth of information — and even a new condition. We know that women can have heart attacks without blocked arteries, but until recently, researchers didn’t know why.
“By looking in more detail at women with heart disease, we identified a condition called microvascular dysfunction,” Pilote says. “Now we understand that the problem is in how small blood vessels feed large ones. The next step is to find a better way to make this diagnosis and a precise treatment for women and heart disease.” Sexual and reproductive health
Most people keeping up to date on health care will have heard of the “gut microbiome,” the tiny organisms that live in our intestinal tracts. As it turns out, vaginas also have microbiomes — and that unique community of bacteria can have a huge impact on women’s health.
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“If women have a healthy microbiome, they’re much better able to fight off STIs like gonorrhea, chlamydia and even HPV,” says Money. “They’re also more likely to have a good pregnancy outcome and less likely to have complications if they need to have a surgery in that area, like a hysterectomy.”
But what counts as “healthy”? To find out, Money conducted a study of women in several different situations and life stages — but she didn’t look just at their cells. She also worked with a social scientist, who helped her pinpoint the behavioural factors that contributed to changes in the women’s microbiomes. In the future, Money hopes, this research will lead to tests that can better diagnose imbalances in the vaginal microbiome, and to targeted treatments that can correct those imbalances.
For Clifford Librach, associate professor in the University of Toronto’s Department of Obstetrics and Gynaecology, associate scientist at Sunnybrook Research Institute and director of the Create Fertility Centre, the potential of precision medicine is wide-reaching. “It will allow us to better predict the age of menopause for a woman so that treatments to prevent osteoporosis, heart disease and stroke — which increase after menopause — can be tailored for the individual,” he says.
And there will certainly be an impact on fertility, he says, whether it’s better methods of diagnosing infertility or increasing the effectiveness of in vitro fertilization. There’s even research being done about how parents’ diets can affect their future offspring’s long-term health. (Maternal diet during pregnancy is closely linked to type 2 diabetes, heart disease due to obesity, insulin resistance and hypertension.) “I predict that specific, precision-medicine-based dietary changes before conception will allow men and women to improve the ultimate health of their offspring,” says Librach.
If there’s any field of health care that has been leading the way in this approach, it’s care for cancer, and particularly breast cancer. Though we’ve only recently begun talking about precision medicine, much of the previous research into breast cancer falls under its umbrella, dating back to the ’80s with the discovery of estrogen-receptor-negative and -positive cancers. (Those who are ER-positive are treated with drugs that target their hormones; those who are negative aren’t.)
“We have been subdividing and classifying patients, directing them to therapies that would or would not be effective, for years,” says Judith Hugh, director of the Division of Anatomical Pathology at the University of Alberta and co-lead for breast cancer testing in the province.
New tests like Prosigna, which was recently approved for use in British Columbia and Alberta, look at various genes to see if a mutation in one of them is causing a woman’s breast cancer, determine that person’s risk factors (for example, the 10-year risk of recurrence or the likelihood that the cancer will spread beyond the breast) and help researchers develop targeted therapies that turn on or off these defective genes.
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And there’s another area of breast cancer that’s seeing huge progress: ductal carcinoma in situ (DCIS), or precancerous lesions. DCIS isn’t cancer, according to Eileen Rakovitch, radiation oncologist and medical director of the Louise Temerty Breast Cancer Centre at Sunnybrook Research Institute in Toronto. “But it can become cancer, and that’s been really challenging for us,” she says. “We haven’t had good tools that allow us to say, ‘You’re at very low risk; you don’t need to do anything’ or ‘You’re at higher risk; you should have chemo or radiation. ’” Now, though, genomic testing is allowing doctors to identify a woman’s risk of getting cancer, which could prevent the unnecessary treatment of those who won’t.
Despite precision medicine’s potential, it has its critics. For some, the trouble lies in the implementation of this approach. For precision medicine to really be effective, patients need access to genetic testing from their primary care provider, not just from specialists or at hospitals. But when doctors aren’t properly trained in interpreting genetic tests, it can lead to adverse outcomes for their patients. Another practical problem is cost. Many scientists argue that, since precision treatments will be more efficient, the overall cost of health care will come down. Until targeted treatments become mainstream, though, it’s difficult to know if that’s true — and it doesn’t change the fact that these drugs don’t come cheap. (Novartis set the price for Kymriah, the leukemia drug, at US$475,000 for one course of treatment.) There are also real privacy concerns: Learning you’re at high risk for cancer or cardiovascular disease can affect your ability to get insurance, and even if you are granted coverage, your premiums are likely to be high. And finally, as we’re learning with other new technological advances like artificial intelligence, algorithms aren’t colour- or gender-blind. In the same way that most participants in clinical trials are men, most participants in genome studies are white. But when scientists study only one ethnic group, their learnings may not apply to patients of other ethnicities.
Then there’s the issue of time. We’re still years, if not lifetimes, away from a health care revolution. A Star Trek–style health scanner that analyzes all your health data to help doctors pinpoint what’s wrong with you and exactly what genetic mutation is causing the illness may never come to pass. But it’s likely your doctor will soon be able to send you to the lab for some simple blood tests that will yield ever more specific information about your health: your risk for life-threatening diseases, yes, but also insight into what preventive measures will be most effective for you and what drugs you’ll respond to best. The entire system may not be overhauled, but these incremental changes will have a huge impact on the way we diagnose, treat and prevent disease.