Shelley Force Aldred was in college studying biology when, in 1994, researchers first discovered a breast cancer gene, BRCA1. “I thought that was the coolest thing ever,” she says. “That was before I knew how complex genetics is. I remember thinking, ‘Wow, we’ve got this solved. We’ve figured it out.’”

She had reason to be excited. As someone whose great-grandmother, grandmother and mother all developed cancer before they turned 35, Force Aldred had a particular interest in breast cancer genes.

I was aware that I was getting to an age when I needed to deal with my risk more concretely. Shelley Force Aldred

She now knows that finding the gene and getting a genetic test are only the beginning. “When you get tested, you immediately think about all the medical implications. It’s not until later that you realize how a diagnosis will affect your whole life,” she says. That’s a lesson that has emerged in the past decade as more tests have become available and more people learn whether they have a genetic risk for cancer. These days, the Stanford Cancer Center offers close to 20 genetic tests for people with a strong family history of cancer.

One new feature of life for many of these at-risk people is being surveyed, poked, prodded and worse in clinical trials seeking to prevent cancer or, if nothing else, to figure out how best to detect early cancer in those whose risk is high. Force Aldred has been involved in three Stanford trials. For her and others whose cancer risk is unusually high, playing the role of a guinea pig has its rewards. It’s a great way to get more regular screening. “Everybody knows that with breast cancer, the earlier you catch it the better your chances are,” says Force Aldred. Participating also provides access to experts who can help navigate the decision-making minefield of life for patients with a genetic risk of cancer.

Force Aldred has had a front row seat, watching the field of breast cancer genetics expand even as her own knowledge of genetics grew through an undergraduate degree in biology and a PhD in genetics from Stanford. Through this, she went from her initial feeling that the disease was cured to an active role in learning how to prevent the disease in herself and others. She has also learned that no decision relating to her cancer risk is without its complications.

Healthy?

At 31, Force Aldred is the very picture of health. She’s fit, trim, upbeat and excited about her future. Now president of the Menlo Park-based startup Switchgear Genomics, Force Aldred says that initially she didn’t realize how her own increased risk would trickle into every aspect of her life. She thought finding the genetic culprit would be the hard part.

There’s the fear. “Any little ache or pain could be cancer,” she says. In fact, that sense of impending doom is so common it has a name: Damocles syndrome. “I was so relieved to know that I wasn’t just crazy,” Force Aldred says. According to Greek legend, Damocles was treated to a luxurious meal at court, but couldn’t enjoy the food and wine because of a sword dangling by a hair overhead. Every bite might be his last.

That fear could drive Force Aldred to panicked exercise and compulsive label checking, but she says she’s all about moderation. She exercises, she eats well and she stays a healthy weight. “I don’t think it’s healthy to be overzealous about that stuff,” she says. Still, at an interview over lunch, her salad fit a dietician’s profile of an ideal meal. Vegetables and lean meat, while she discusses her exercise habits. There’s overzealous and then there’s a level-headed awareness of the sword’s presence.

And there’s insurance. She or her husband must always have a group health plan. Given her rigorous testing, she’d go broke with individual coverage. Then there’s the issue of what to tell the insurer. When Force Aldred was getting tested for cancer-causing mutations, her genetic counselor, Nicolette Chun, discussed the pros and cons of paying for the test herself to keep the results off the insurance records. She went ahead and submitted the claim: “I realized if the tests came back positive, insurance would need to know so they would pay for all the testing I get done,” she says. She gets screened for one thing or another at least twice a year, plus a few extra visits for trials.

And then there’s work. And friends. Whom do you tell? What if you, say, want to start a company? Do you share your family’s cancer history with funders? Investors, after all, prefer investees to be on the job — not in the hospital. Preferably alive.

Do you tell nosy writers about your family history, knowing that their stories live forever on the Web? Admitting to a strong family history in print could have consequences decades in the future.

If you are Force Aldred, you tell. “I’m pretty open about it,” she says. “Our team needs to know why I’m not in the office sometimes. I get a lot of testing and I take my health very seriously. They need to know my reasons for being so vigilant about my health.” Force Aldred has another reason for being so open. “It lets me get on my soapbox about how everyone needs to understand his or her family health history.”

If she hadn’t been so aggressive about tracking down her family history and seeking out genetic counseling, she might not be receiving the intensive screening that could well save her life.

Hooked on genetics

It wasn’t until a high school biology class on genetics that Force Aldred made the connection between genes and her family history, she says. “That made a big impression on me,” she says. That’s when she realized that a mutation might be responsible for her family risk. And when she decided that genetics was extremely cool.

She ended up in Stanford’s genetics department working with professor Richard Myers, PhD, studying DNA segments that switch genes on and off. That topic didn’t do much to further what she knew about cancer, but she quickly picked up that finding a gene is a long way from curing a disease.

So much for that “aha” moment as an undergrad when the discovery of a breast cancer gene was first announced.

But the discovery of BRCA1 did lead to changes. The most immediate was the availability of a genetic test for mutations in the gene. With that, women who knew the disease ran in their family could get tested to find out if that gene was to blame.

If a woman learned she was free of the mutation causing her family’s cancer, she would go from a lifetime of worrying about breast cancer to relief. She could also forgo radical preventive steps, such as surgically removing her breasts or ovaries.

Essentially, getting tested revealed the presence or absence of a dangling sword. “Having a predictive test is huge. You can set someone free with that,” says one of Force Aldred’s doctors, Allison Kurian, MD, assistant professor of oncology, who runs trials for women at risk of breast cancer. “It’s a wonderful feeling to tell someone they don’t have the mutations.”

Then came the discovery of BRCA2, in 1995, which, together with BRCA1 accounts for about 80 percent of inherited breast and ovarian cancers. That was quickly followed by the discovery of several other mutations that convey a substantial cancer risk.

Force Aldred says those gene discoveries have opened up a world of possibilities for people with inherited risk. “It has given scientists the ability to study people with the mutations and learn how to prevent or detect cancers,” she says. “It’s not a cure, but that’s big.”

Big enough to convince even those with a less-scientific bent than Force Aldred to get tested. Rachel Paley, a Palo Alto resident who tested positive for a BRCA1 mutation, says genetic counselors had an uphill climb to teach her what a mutation meant. “They had to go over and over the material with me,” she says. She and her sister got tested after their mother developed ovarian cancer at an early age. (BRCA1 mutations also increase the risk of ovarian cancer.)

Because she learned she had the mutation, Paley knew getting her ovaries removed was a wise choice, but she still wanted kids. She opted for increased screening until she’d had two kids, then had her ovaries removed. She is also plugged into a support group of other women making similar health decisions. “You have to have people who talk about what it’s like to go through it,” she says. For example, although ovarian cancer runs in her family, it’s caused by a BRCA1 mutation that is primarily associated with breast cancer. “I’ve been talking to other women about whether or not to have a mastectomy to eliminate that risk,” she says.

Risky business

Force Aldred’s involvement with Stanford’s cancer genetics clinic came at an auspicious time to see the genetic discoveries translated into practical solutions.

Her first encounter was in 2000 when she was in her mid-20s. “I was aware that I was getting to an age when I needed to deal with my risk more concretely. I needed to figure out how to be proactive,” she says. At that time she was just starting out as a Stanford graduate student.

As luck would have it, her department had recently hired James Ford, MD, associate professor of oncology and of genetics who now runs the cancer genetics clinic. Although his interest had been in hereditary colon cancer, he was ramping up work in hereditary breast cancer.

This was around the same time that Paley first came to the clinic. For both Paley and Force Aldred, their initial involvement with the group was informal — getting genetic counseling and setting up a screening strategy. They worked with Chun to gather information about family history, connect with the best physicians and navigate insurance.

Help with insurance is no small thing. Force Aldred once had a fight over claims for scans of her left and right breasts that were rejected for entirely different reasons. “Clearly left and right breasts are significantly different in the eyes of the insurance company,” says Force Aldred, who has fought more than her share of unusual insurance rejections.

Part of the problem is that consensus on care for people with these mutations is utterly lacking. Obviously, they should get screened more often than those without mutations, but is twice a year enough? Is a different type of screening needed? Will certain drugs prevent cancer? Nobody knows. Not even Force Aldred’s doctors agree on which screenings she should get. And insurance isn’t interested in paying for guesswork.

Sometimes even supposed experts fail to grasp the meaning of family history when it comes to cancer risk. Once, on a first visit to a new doctor, Force Aldred had to deliver a genetics lecture to convince her new doctor to treat her. “I couldn’t believe it,” she says of the experience. “People who are supposed to be treating me don’t even understand basic genetics.” It didn’t exactly instill confidence in someone newly diagnosed and intent on receiving the best possible care. It also drove home the difficulty of knowing which medical treatment is most appropriate.

These experiences are why Force Aldred is such an advocate for people to understand their own health risks. If she hadn’t known better, she might’ve taken the advice one misguided doctor gave her: Chill out and quit worrying about all those relatives who died of cancer. In their 30s.

It’s this kind of ambiguity that gets people involved in trials.

Looking back on her experiences as a trial participant so far, Force Aldred says ductal lavage was the worst. That’s where researchers essentially rinse the very sensitive milk ducts of the nipple and look for early cancers in the cells that wash out. “Some people think the mammogram hurts more, but I think they’re crazy,” she says. She went through that five times.

Then there’s the drug she took in the hopes that it staves off breast cancer. The drug, lovastatin, is commonly taken by people with high cholesterol. “We were on a really high dose,” she says. Muscle pain, headaches and nausea were a hefty price for a drug that may or may not lower cancer risk.

And then there are the MRIs to search for early signs of cancer, in addition to regular mammograms.

The thought was that MRI might better detect the types of tumors women with a family history tend to develop. Since then, getting MRI screenings has become the standard of care for women with a family history of breast cancer. “The benefits of MRI are something we couldn’t have learned without people participating in the trials,” says Kurian.

Although Force Aldred’s scientific background probably makes her more accepting of clinical trials than most, she doesn’t think it’s her primary motivator. “I can’t imagine having that risk and not wanting to do everything I can to prevent cancer,” she says. Paley, who participated in two trials with Kurian, goes even further. “It takes a huge amount of time. I wouldn’t be motivated if I weren’t at risk.”

Paley says that in addition to learning how to prevent cancer, being part of trials keeps her connected and gives her access to the experts. “If I see something about breast cancer in the news, I can e-mail Dr. Kurian and ask what’s behind it. You don’t have access to that knowledge without being in trials.”

She even liked the biopsies, the memory of which makes Force Aldred grimace. “I was stuck in a room for hours with these really smart people. I got to ask all these questions. It was invaluable,” Paley says. “I remember lying there saying, ‘Now tell me again how the mutation leads to cancer,’ and they explained it all again.” Like Force Aldred, Paley participated in the lovastatin trial and received several rounds of ductal lavage.

For both Paley and Force Aldred, participating in the trials is just one of many ways their lives differed dramatically from what they would have been without testing. They’ve both also had to make decisions about children. Paley’s might have inherited the mutation; she will talk to them about testing when they are older, she says. Force Aldred has chosen to adopt.

Looking ahead, Force Aldred says she plans to be part of another start-up and is hoping to retire by age 50. It’s not just that she’s a careful planner. It’s that life requires a bit more forethought when the cancer sword could drop at any time.

In the meantime, being proactive about her health and participating in trials might strengthen the hair or perhaps dull the blade. Either is better than doing nothing or running scared.

Is just one of many ways their lives differed dramatically had they never been tested. They’ve also had to make decisions about children. Paley’s might have inherited the mutation; she will talk to them about testing when they are older, she says. Force Aldred has chosen to adopt.

Looking ahead, Force Aldred says she plans to be part of another start-up and is hoping to retire by age 50. It’s not just that she’s a careful planner. It’s that life requires a bit more forethought when the cancer sword could drop at any time.

In the meantime, being proactive about her health and participating in trials might strengthen the hair or perhaps dull the blade. Either is better than doing nothing or running scared.