Family Struggles With Ambiguity Of Genetic Testing

Susan Gilmore with her family. i i

The Gilmore family, from left, Josephine, Susan, Alice, Dan and Claudia. David Deal for NPR hide caption

itoggle caption David Deal for NPR
Susan Gilmore with her family.

The Gilmore family, from left, Josephine, Susan, Alice, Dan and Claudia.

David Deal for NPR
Susan Gilmore and her husband Dan Gilmore. i i

Susan Gregg Gilmore and her husband, Dan, struggled with major health decisions after receiving genetic testing results. David Deal for NPR hide caption

itoggle caption David Deal for NPR
Susan Gilmore and her husband Dan Gilmore.

Susan Gregg Gilmore and her husband, Dan, struggled with major health decisions after receiving genetic testing results.

David Deal for NPR
Martha Gilmore and granddaughters. i i

Martha Gilmore, who was diagnosed with breast and ovarian cancer, is seen with her granddaughters, from left, Alice, Claudia and Josephine. Family photo courtesy of Susan Gregg Gilmore hide caption

itoggle caption Family photo courtesy of Susan Gregg Gilmore
Martha Gilmore and granddaughters.

Martha Gilmore, who was diagnosed with breast and ovarian cancer, is seen with her granddaughters, from left, Alice, Claudia, and Josephine. Martha encouraged her family to get tested for the BRCA-1 gene mutation before she died.

Family photo courtesy of Susan Gregg Gilmore
Susan and Dan Gilmore's three daughters i i

Claudia, 21, (right) has already chosen to have genetic testing. Josephine, 17, and Alice, 14, will make this decision when they get older. David Deal for NPR hide caption

itoggle caption David Deal for NPR
Susan and Dan Gilmore's three daughters

Claudia, 21, (right) has already chosen to have genetic testing. Josephine, 17, and Alice, 14, will make this decision when they get older.

David Deal for NPR

"Information is power," has become a common mantra. But for many people seeking answers through genetic testing, all the DNA probing ends in this twist: Less certainty, not more.

This sometimes leads to tough personal decisions amid ambiguity. Nashville novelist Susan Gregg Gilmore learned this lesson the hard way.

Gilmore, a happily married, 47-year-old mother of three daughters, sought testing for flaws in two long genes known as BRCA 1 and BRCA 2. A number of mutations in those genes, first identified in the mid-1990s, have been strongly associated with an increased risk of breast and ovarian cancers.

The risk is particularly elevated for women; having one of the harmful mutations increases the lifetime risk of breast cancer to somewhere between 36 percent and 85 percent, according to the National Cancer Institute. The range reflects the differing risk estimates that have turned up in different studies. A BRCA mutation increases the ovarian cancer risk to between 16 percent and 60 percent.

Though she had heard of the test, Gilmore says, she never thought much about it before getting a call from her mother-in-law, Martha, a few years ago. Eighteen months after defeating breast cancer, Martha Gilmore, a Methodist minister, was diagnosed with ovarian cancer, at age 63. Though most cases of breast and ovarian cancer are not inherited, Martha and her doctors wondered if a BRCA mutation might be behind both diseases in her case. She had called to tell Susan that she was considering taking the test so that her children and grandchildren would have more information.

The Power Of Information

Susan was very close to her mother-in-law, and was encouraging that day.

"I remember saying 'Martha, you've got to do this. I mean information is knowledge and power. We have three daughters ... Yes, yes. We need to know.' But in no way did I realize at the time what kind of impact that test would have on my life," she recalls.

Martha did turn out to have one of the mutations in BRCA 1 that's been tied to cancer. Eventually, she died of the illness, with Susan and other family members at her bedside. And not long after Martha's funeral, further testing showed that her son Dan Gilmore — Susan's husband — had also inherited the mutation.

Susan was out of town that day, and when Dan called from the clinic to tell her the bad news, she fell apart.

"It really threw us for a loop," he says. "We were not as emotionally prepared for it as we should have been."

Now, you could argue that Dan's genetic test result really had implications only for him and his three daughters, who are now in their teens and early 20s. But as Dan and Susan started scrambling to get more information, Susan started worrying about her own DNA.

One aunt, she recalled, had suffered a chronic disease of the ovaries, and eventually died of ovarian cancer. To Susan, who was still reeling from her mother-in-law's terrible illness, the aunt's death seemed ominous. And that wasn't all.

"As we're sitting there with a genetic counselor plotting out our family tree — Dan's family tree — I'm kind of looking at the tree and putting my own family members on the branches," says Susan, "and realizing that there are some missing branches!"

She had the sort of gaps that are common in an extended family's medical history. "My mother's mother had died at a very young age, in her early 30s," Susan says. "And no one seemed to know why."

According to family lore, Susan's grandmother might have died of a botched abortion. Others said it could have been cancer. Such vagueness isn't unusual.

"But it puzzled me and terrified me," Susan says.

Taking It A Step Further

The best solution, she decided, would be to get tested herself for BRCA mutations. It would put her mind at rest, and give her daughters "a more complete medical history on both sides of our family." Susan's mother is still alive and healthy, and Susan has lots of middle-aged female cousins and sisters who are all cancer-free. The doctors told her it was extremely unlikely she had a BRCA mutation. All the more reason to get tested, she thought.

"I wanted to bring some good news to the table," she says.

Dan, a pragmatic attorney and marathon-running former Marine, was initially worried that this time the test was just inviting more trouble. But he eventually came around to Susan's view.

"Chances are she doesn't have it," Dan figured. "This'll sure be nice to rule this out."

So Susan got tested, and remembers exactly where she was, a week or so later, when she got the news.

"I walked out of the Y that day," she says. "It was a beautiful day. It was crisp, it was clear. And I remember standing in the parking lot thinking, 'I feel good.' And for the first time in months I do not feel like cancer is going to control my life, or even the thought of cancer. Or the fear of cancer. And not even five minutes later, I get a call on my cell phone."

It was the genetic counselor. Susan still winces remembering the words that came next.

"She started talking about this variant, this variant of 'undetermined significance,'" Susan says, "and how it shouldn't change my life or my medical plan. But, you know, all I could hear was variant ...and it wasn't really making any sense. And it felt ... it felt overwhelmingly gray."

Susan and her family had been counting on good news — or at least a clear thumbs up or thumbs down. But, as the counselor explained, a variant mutation of "undetermined significance" turns up in roughly 10 percent of all case of BRCA tests, and even more often among African-American families. It means there is definitely a mutation, but one that hasn't been linked to illness, in all the research that's been done so far. Susan's "variant" could turn out to be harmless ... or not. At this point, no one can say for sure.

Determining Where To Go From Here

Susan was far from comforted.

"I thought, 'Can we not catch a break here in this genetics game? And what is this variant? And quit telling me that it's of undetermined significance, because I can tell you right now, it is feeling extremely significant," she says.

What she really wanted to know, she says, was whether she should she have her ovaries removed, "just in case." She consulted several doctors and genetic counselors, but, much to Susan's frustration, they all stopped short of direct advice.

"I totally relate to the frustration," says Beth Peshkin, a genetic counselor the family consulted at the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, D.C. "Because I think, as clinicians, we would like to have more definitive answers as well."

As Peshkin explained to Susan, the BRCA test has proved to be quite helpful over the years, particularly to families who have a widespread family history of ovarian and breast cancer across several generations. Once the particular mutation has been identified that's behind a family's cancer, any member who tests negative for that mutation can be considered truly negative. That's the good news result. The risk of that person getting cancer is no higher than the risk among the general population, and those who get that news can be certain they won't pass the family cancer gene on to their children.

Even a "bad news" test result — knowing that they have a harmful mutation — feels empowering to many people, Peshkin says, because it prompts them to get more frequent screening for breast cancer. Any tumors subsequently discovered are likely to have been caught at an earlier, more treatable stage. Some women in that situation choose prophylactic mastectomies as a further hedge against disease. And, because there are no good screening tools yet for ovarian cancer, some women who discover they have harmful BRCA mutations are choosing to have healthy ovaries removed in their mid-30s, once they are done with childbirth. Though never an easy choice, such surgery does greatly reduce the risk of cancer.

But the catch is this: Increasingly, with more healthy people from healthy families seeking testing than ever before, the results coming back are often much harder to interpret.

"Today," Peshkin says, "maybe half the people seeking BRCA testing get back results that are uninformative for one reason or another."

Letting Tolerance Level For Risk Be The Guide

Some, like Susan, have an ambiguous variant that may or may not be normal. Others are told they are "negative" for all known BRCA mutations, but because they have many cases of cancer in their family, it seems likely that a different flawed bit of genetic machinery that has yet to be identified is to blame for the family's disease. In these cases, patients are told that their test result is negative, but not necessarily a "true negative."

Whatever the cause of the uncertainty, research studies have shown that such ambiguous news is often at least as distressing to hear as bad news, at least in the beginning. As Peshkin tried to help Susan work out what to do next, she advised the anxious patient to let her own tolerance for risk serve as a guide.

"In this case," Peshkin says, "it really came down to, 'It doesn't look based on your family history or your test result that you're at increased risk for ovarian cancer. But you're very worried about this disease; there isn't good screening for this disease; we can't tell you conclusively what your risk is.' So, it really did have to be her decision."

Susan says that even if the science suggests her cancer risk is minimal, those statistics can't wash away her experience of her mother-in-law's final days.

"Doctors can tell me that ovarian cancer is very rare," she says. "But then I can say, you know, I've known more people with ovarian cancer than breast cancer. I have held the hand of a woman dying of ovarian cancer. So, in my reality, ovarian cancer is very present."

So, last June, Susan decided to have her healthy ovaries removed. Dan supported his wife's decision, and Susan says she doesn't regret the surgery for a minute. She now knows she's done everything she can to eliminate any risk of ovarian cancer.

Peshkin agrees that, for Susan, the surgery was justifiable. But is she better for having taken the genetic test in the first place?

"I don't know," says Peshkin. "In some ways probably yes, in some ways probably no. But this is what it is to live with uncertainty. And some people have a harder time living with uncertainty than others."

Looking At Their Daughters' Futures

Through it all, Susan and Dan believe they've been good role models for their children. They were supportive when, earlier this fall, their 21-year-old daughter Claudia, the eldest, decided to get tested. Claudia has inherited Dan's mutation.

In many ways, Susan says, that was the hardest news to get of all.

"Knowing that from the time she's 25, every six months she'll have to have ... a mammogram or MRI ... and biopsies whenever they pick something up ... all that testing anxiety and decisions. Do I have my breasts removed? My ovaries removed? Sure, it's life-saving information, but it's a lot of muck, and there's a sadness to that," Susan says.

"As a parent, you know bad things are going to happen to your kids," she says. "But it's a very different feeling when you are the ones handing them the muck. It's an unnerving feeling to have to say, 'Here — we know what this is, and we're giving it to you. Now make something of it.'"

For now, that new knowledge just means extra breast exams for Claudia. Dan says that genetic testing for the two younger girls, who are still in their teens, can wait.

"There's the whole ethical issue of them having a choice in it," he says. "We really felt like they needed to be old enough to decide on their own, to make it a fully informed decision on their own."

Susan says she's content with all the family's decisions so far. Still, she's in no big rush to sign up for further genetic testing for other diseases.

"I mean, this year alone ya know, all the genetic testing that my husband's done—my mother, my daughter, myself—I'm kinda done. I mean, I want a year off from empowering knowledge. At some point, you've just got to get out there and live life," Susan says.

Deborah Franklin reported this story during her time as a Kaiser Family Foundation fellow.

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