Previvors

Actress Angelina Jolie made headlines when she revealed that she’d had a double mastectomy after learning she carried a BRCA gene mutation. But well before she ‘came out,’ a number of local women were taking their own preemptive action.



Illustration by Libby Burns

For generations, no one realized that a killer was stalking the women in Lisa Schlager’s family.

Her father’s maternal grandmother died in her late 40s of what the family described as “female issues.” And her father’s mother died from what her family thought was lung cancer.

It wasn’t until her father’s younger sister, Ronni, was diagnosed with premenopausal breast cancer that the true identity of her grandmother’s and great-grandmother’s likely killer was revealed: a mutation in a BRCA—for “breast cancer susceptibility”—gene, which sends women’s risk of breast cancer as well as ovarian cancer soaring.

Only a small proportion of breast and ovarian cancers are hereditary, but mutations in the two BRCA (commonly pronounced “braca”) genes account for the bulk of them—5 percent to 10 percent of all breast cancers, and 10 percent to 15 percent of all ovarian cancers, according to the National Cancer Institute. In people without mutations, the BRCA genes help prevent tumor growth.

After her Aunt Ronni tested positive for a BRCA mutation, Schlager, the next oldest woman in the family at age 31, decided to get tested. While awaiting the results, Schlager recalls, “I tried not to think about it. I felt a little bit invincible. I was pretty surprised when the results came back positive for the mutation. This is heavy information, and there’s a lot that goes along with it.”

Today, the 46-year-old Chevy Chase resident serves as vice president for community affairs and public policy at FORCE, or Facing Our Risk of Cancer Empowered, a national nonprofit dedicated to improving the lives of individuals and families affected by hereditary breast and ovarian cancer.

If a woman knows she has a BRCA mutation, she can take steps—earlier and more frequent screening; “chemoprevention” with drugs such as tamoxifen; and prophylactic surgery—to reduce the chances that she’ll develop and possibly die from breast or ovarian cancer. More than a decade ago, FORCE coined the term “previvor” to describe women who have survived a genetic predisposition to breast and ovarian cancer, as opposed to surviving the disease itself.

Actress Angelina Jolie became the world’s best known previvor when she “came out” last May in a New York Times op-ed piece. She wrote about testing positive for a BRCA mutation and having a prophylactic double mastectomy and reconstructive surgery. Her mother died in 2007 of ovarian cancer, and her mother’s sister, who also had a BRCA mutation, died of breast cancer days after Jolie’s op-ed piece appeared.

“This has certainly brought hereditary cancer out of the closet,” Schlager says of Jolie’s announcement. “We’ve never had so many media requests. Our Facebook page and website had more hits than ever, and calls to our helpline quadrupled.”

About one in 500 people in the general U.S. population has a BRCA mutation—nearly 1 million Americans, according to FORCE. But among Ashkenazi Jews—those of European descent like Schlager—one in 40 has a mutation. Thousands of BRCA mutations have been identified, but three in particular are associated with most hereditary breast and ovarian cancers in Ashkenazi Jews.

About 12 percent of women in the general U.S. population will develop breast cancer sometime in their lives, but those with BRCA1 or BRCA2 mutations have at least a 60 percent chance—or at least five times that of women without a mutation.

Breast cancers in women with BRCA mutations tend to be diagnosed at an earlier age, often before menopause, than in women without such mutations. BRCA mutations also increase the lifetime risk of ovarian cancer 10- to 30-fold, from 1.4 percent seen in the general population to 15 percent to 40 percent. In addition, both women and men with BRCA mutations might have an increased risk of other tumors, including pancreatic cancer.

Geneticist Mary-Claire King, now at the University of Washington in Seattle, provided the first evidence that the BRCA1 gene existed back in 1990 while working at the University of California, Berkeley. (In interviews, she has said that BRCA is named for Berkeley, Calif., as well as breast cancer.) Until this year, Myriad Genetics, a Salt Lake City company, was the sole marketer of a blood test for mutations in the genes, providing BRCA testing to a quarter of a million people each year in the United States and elsewhere since 1996. But in June, the U.S. Supreme Court ruled that the company’s patents of the BRCA1 and BRCA2 genes were illegal. That ruling was expected to open up the BRCA testing market and lower the cost—and indeed, a Houston company announced that same day that it would begin offering the testing for $995 versus the roughly $4,000 Myriad had been charging.

BRCA testing is not recommended for women who’ve never had breast or ovarian cancer and don’t have a family history of either disease, although some scientists have suggested that Ashkenazi women should be routinely tested, given how common mutations are in that population.

Just because your grandmother was diagnosed with breast cancer at the age of 75 doesn’t mean the disease runs in your family, notes nurse practitioner Jennifer Loud, assistant chief of the clinical genetics branch of the Division of Cancer Epidemiology & Genetics at the National Cancer Institute, part of the National Institutes of Health in Bethesda. However, if a male relative has had breast cancer or multiple female relatives have had ovarian and/or breast cancer, especially in both breasts, “well, this is starting to have that hereditary cancer flavor,” Loud says. “We would always like to test one family member who had cancer.” If that individual is found to have a BRCA mutation, then other family members could be tested to see if they have the same mutation.

Jolie’s announcement spurred many anxious women to call the Suburban Hospital Breast Center in Bethesda, says Dr. Pamela Wright, a breast surgeon and the center’s medical director. “With a lot of these women, their perceived risk is so much higher than their actual risk,” Wright says.

Computer models based on family history can help estimate the likelihood of having a BRCA mutation. “Sometimes women are very pleasantly surprised that their risk estimates are lower than they thought,” says Dr. Carolyn Hendricks, an oncologist who specializes in breast cancer at Suburban.

The fact that Schlager had a BRCA2 mutation meant that her father had to have passed it on to her. His mother, who likely had breast or ovarian cancer and not primary lung cancer, must have passed the mutation to him. And his maternal grandmother’s lethal “female issues” presumably were breast and/or ovarian cancer. Each child of an individual with a mutation has a 50 percent chance of inheriting it. Schlager’s cousin, the daughter of her Aunt Ronni, won the coin toss and tested negative.

After Schlager tested positive in 1999, she discussed her options with a surgeon. But she was taken aback when the doctor asked straightaway: “So when are we scheduling surgery?”

Schlager was married but hadn’t yet had children, so she wasn’t ready to remove her breasts, ovaries and fallopian tubes, the most effective way for women with BRCA mutations to reduce their cancer risk. Instead, she opted for stepped-up screening. She alternated mammograms with an MRI of her breasts every six months. To screen for ovarian cancer, she underwent a transvaginal sonogram and a CA-125 blood test every year. CA- (or “cancer antigen”) 125 is a protein present on the surface of many ovarian cancer cells. The test has a high false-positive rate, so it’s not routinely used to screen average-risk women.

“Surgery is not the only option,” Schlager says. “You have to do what is right for you.”

However, screening for ovarian cancer “has proved to be a remarkably difficult challenge,” Loud says, and the disease usually isn’t diagnosed until it’s at an advanced stage. Schlager acknowledges the ovarian screening tools “aren’t very reliable,” but “they’re all we have.”

Loud says she has known high-risk women who put off prophylactic surgery for decades. “All of a sudden they’re ready. I can’t put my finger on why exactly. It may be related to just a little bit of change in worry,” she says. “Sometimes I think they’ve decided they just want to do everything in their power” to avoid cancer.

For Schlager, now a mother of two, “things changed after I had kids. When I reached my 40s, there was a lot more research out. As I approached my 40th birthday, I knew I had to take my ovaries out.”

Removal of the ovaries and fallopian tubes cuts the risk of ovarian cancer in women with BRCA mutations by about 90 percent. In high-risk premenopausal women, it also reduces the breast cancer risk by halting the production of estrogen, which plays a role in the development of the disease.

Schlager had her ovaries and fallopian tubes removed in 2006 at Georgetown University Medical Center and began to seriously consider getting her breasts removed, too.

“All of a sudden I didn’t feel so invincible,” she says. “My MRIs found a few things. I was getting biopsies.” One biopsy was normal, but the other found precancerous cells associated with a five-fold increased risk of breast cancer. It “significantly increased my anxiety level about developing breast cancer,” Schlager recalls. “I had two little kids at home, and all I could think about was how we would manage if I got sick.”

Plus, her doctor was reluctant to put her on hormone therapy—typically prescribed for women who’ve gone through early menopause as a result of having their ovaries removed—while she still had her breasts. Studies have linked postmenopausal hormone therapy to an increased risk of breast cancer.

So in 2007, Schlager underwent a prophylactic, “nipple-sparing” double mastectomy followed by reconstructive surgery at Georgetown. These days, she’s happy to duck into a restroom and unbutton her shirt to show her results to any woman considering the operations.

 

Lisa Schlager (left) of Chevy Chase and Karen Kramer of Potomac both tested positive for the BRCA gene mutation and ultimately chose to have prophylactic surgery. Photo by Stacy Zarin-GoldbergFellow FORCE leader Karen Kramer took a more aggressive course of action. The Potomac resident decided to have prophylactic surgery within a few weeks of learning she had a BRCA2 mutation. But her circumstances were different than Schlager’s.

Kramer, now 48, was already 44 and the mother of three when she tested positive in January 2009.

Her paternal grandmother was diagnosed with breast cancer twice before menopause, so Kramer decided to begin getting annual mammograms at age 30. Along the way, she sweated out the results of two biopsies that turned out to be benign cysts. Her OB-GYN kept telling her not to worry because the breast cancer in her family was on her father’s side—a common misconception, even among doctors. Of course, men can’t get ovarian cancer, and their risk of developing breast cancer is far lower than that of women, but they can still inherit a BRCA mutation and pass it on to their children.

Kramer finally decided to get tested for a BRCA mutation after a first cousin on her father’s side was diagnosed with ductal carcinoma in situ, the earliest-stage breast cancer. Kramer’s radiologist told her that it might be extremely difficult to spot such a malignancy in her dense breasts and, given her family history, recommended genetic counseling.

“I don’t have a striking family history until you really know and look at it,” says Kramer, FORCE’s vice president of marketing. Besides her grandmother, there were her grandmother’s siblings: Her grandmother’s sister died of cancer so widespread that doctors couldn’t pinpoint its origin. Her grandmother’s brother had prostate cancer, another malignancy associated with BRCA2 mutations. His son had prostate cancer, and his daughter had ovarian cancer.

Though Kramer tested positive for one of the Ashkenazi mutations, her cousin with breast cancer, ironically, did not. “My oncologist could not believe that my cousin was negative,” Kramer says. “Apparently she was just unlucky.”

Her cousin’s mother still has a 50 percent chance of having inherited the BRCA2 mutation, but she doesn’t want to be tested. None of Kramer’s other relatives have been diagnosed with cancer. But Kramer’s sister also tested positive for the family’s BRCA2 mutation, though she has decided to forgo prophylactic surgery for now.

It’s one thing to learn you have a BRCA mutation when you’re in your 40s and your family’s complete. It’s another matter when you’re in your 20s and you haven’t yet had the children you hope for, let alone met the man you hope to have them with.

“We see a good number of younger women,” says Judith Macon, a nurse who manages cancer outreach and education at the Suburban Hospital Breast Center. “The bottom line is we encourage women to have the families that they always wanted to have.”

When Beth Landau learned at age 28 that she carried a BRCA2 mutation, she had neither children nor a steady boyfriend.

Landau, who grew up in Olney and now lives in Bethesda, decided to get tested in May 2011 after a 44-year-old first cousin was diagnosed with breast cancer and then found to have the mutation. That cousin’s mother, Landau’s father’s sister, had been diagnosed with postmenopausal breast cancer but hadn’t yet undergone genetic testing.

Landau’s doctor at Kaiser Permanente in Kensington referred her for testing at Genetic Consultants of Maryland in Rockville. “I am the type of person who doesn’t want to sit around and wait for something to happen. I want to know all of my options,” says Landau, who works as a legal assistant in a law office. “Unfortunately, I really didn’t put much thought into how I would use this information in my everyday life. I really regret having that mindset. I wish I would have done some research and known what this meant.”

Thankfully, Landau says, her mother accompanied her to the appointment where she learned she had a BRCA2 mutation. “I just started sobbing, and I wasn’t listening to anything they were saying. As opposed to just being blindsided, I just wish I would have done my research and said to myself: ‘If I have it, I’m going to be OK.’ Do I regret having the testing? I don’t know. Sometimes.”

A couple of months later, Landau’s only sibling, a sister who’s 3½ years older and lives in New York, was also tested. It turns out she, too, inherited the BRCA2 mutation. Because his daughters had the mutation, Landau’s father knew he must, as well, spurring him to get a thorough physical.

In no rush to undergo prophylactic surgery at age 30, Landau has stepped up screening for breast and ovarian cancer. She’s now dating a great guy, and “we’ve always been very open and honest with each other. I told him about carrying the BRCA gene [mutation] pretty early on. We didn’t necessarily talk about having kids at that point.”

Still, she says, “it was definitely a difficult decision to tell him.”

A former USA Today health writer, Rita Rubin lives in Bethesda.

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