Published June 19. 2013 4:00AM Updated June 21. 2013 1:28PM
When actress Angelina Jolie wrote recently in The New York Times about her decision to have a bilateral mastectomy, the removal of both breasts, because she carried a genetic mutation that increased her chances of getting breast cancer, her revelation focused worldwide attention on the culprit: the BRCA genes.
"The phone was ringing off the hook all day; it was remarkable how it raised public awareness, " said Dr. Anees Chagpar, director of the Breast Cancer Center at Yale-New Haven's Smilow Cancer Hospital.
For Madison's Dr. Andrea Schaffner, who practices with Middlesex Hospital-Primary Care in Essex, Jolie's revelation was nothing new. She, too, had tested positive for one of the two BRCA gene mutations, and had undergone the same operation: a bilateral mastectomy, eight years ago. (The term BRCA comes from the first two letters of the words breast cancer.)
Jolie's mother had died of breast cancer at 56. Schaffner's mother, grandmother, and great-grandmother had all suffered from breast cancer, though none had died from it. A cousin, however, died of breast cancer at the age of 50.
What initially convinced Schaffner, nonetheless, to see if she herself carried either one of the BRCA gene mutations, was not family history but the request of a patient, whose own medical history had prompted her to ask for the test to determine if BRCA gene mutations were present. The procedure involves drawing blood, sending it to a testing lab, and awaiting the results.
When they came back, the patient's results were negative. Schaffner's were not. She had a mutation in the BRCA2 gene; Jolie had a mutation in the BRCA1 gene.
"I'll never forget that day," Schaffner recalled.
She said that it reminded her of a scene in the movie Back to the Future. Lead actor Michael J. Fox as Marty McFly, a teenager who had been transported back in time 30 years, sees his image begin to disappear from a family picture when it looks as if the two young people, who were to become his parents, would not marry.
"I could see myself disappearing like that," Schaffner said.
Overall, however, only a small percentage of breast cancers are caused by the two BRCA gene mutations, which also increase the risk of ovarian cancer, but in women who have been found to carry the BRCA mutation, the risk changes markedly, rising to 60 to 65 percent-and that is not the end of the story.
For Jews from Central and Eastern Europe, known as Ashkenazi Jews-like Schaffer and the patient who came to her requesting the test-the rate is even higher. On average, one in 40 women of Ashkenazi Jewish heritage will carry BRCA gene mutations. Ashkenazi Jewish men also have a higher incidence of breast cancer, though not nearly as elevated as women.
Still, ethnicity alone isn't reason enough to have tests for the BRCA mutations, according to Ellen Matloff, director of Genetic Counseling at Smilow Cancer Hospital. A family history of cancer is what genetic counselors look for.
Up to now, the test itself has been an expensive proposition, costing as much as $3,000, but the expense was actually less for Ashkenazi Jewish women, because the locations of the genetic mutations have been identified in their case.
"Picture BRCA1 and BRCA2 as two telephone books. There are three misprinted numbers, 2 in BRCA1 and 1 in BRCA2, that are seen again and again in Jewish families," Matloff explained. "We know where these three pages are in the phone books and can examine them inexpensively in this population."
Now, however, the cost of the BRCA mutation test may become less for everybody as the result of a recently decided Supreme Court case. Myriad Genetics, the privately owned company that first sequenced the BRCA genes in the 1990s, patented them, arguing that patents were necessary to offset the costs of their research.
With the patent, Myriad laboratories or labs it licensed were the only ones who could work on the BRCA genes, but the Supreme Court's decision invalidated Myriad's claim to a patent, holding that while synthetic genetic material may be patented, a natural sequence of genes may not. According to Yale's Chagpar, the likely result will be that a test for the BRCA gene mutations will become both less expensive and available to more women.
Making the Decision
After she was identified with the BRCA2 gene mutation, Schaffner's first decision was to have an oophorectomy, the removal of her ovaries.
"Ovarian cancer is much worse; I got on the phone right away to my ob-gyn and said, 'I want them out,'" she recalled.
In addition, she sought genetic counseling and talked with professionals at Memorial Sloan-Kettering Cancer Center in New York. At Sloan-Kettering, some experts urged her not to have her breasts removed.
"They were gung-ho not to have surgery," she said.
She was told that she would be put on tamoxifen, a breast-cancer inhibiting drug, and would be monitored regularly. If any cancer developed, she was assured, it would be caught in the early stages.
Schaffner was uncomfortable with the advice.
"Wait a minute, I don't want to catch the cancer early; I don't want to get it at all," she remembered thinking. "I don't want every mammogram to be Russian roulette."
She decided on a bilateral mastectomy. One of her sisters, who tested positive for the gene mutation, also had a bilateral mastectomy and an oophorectomy. A third sister tested negative.
Having the mastectomy before the appearance of cancer, as a preventive measure, may have consequences for subsequent reconstructive breast surgery. Those who have preventive mastectomies, according to Chagpar, are better candidates for surgery that allows them to retain their own nipples. In many patients in whom cancer has already developed, the nipple is removed in the mastectomy and reconstructed later.
Removing a breast, a preeminent symbol of femaleness, is an emotional as well as a medical decision. Schaffner noted there were many websites on which women could discuss their options.
"I'm on listservs where I see people every day asking if they should do this," she said. "When I see people saying they are in a state of shock, there are other people on the website telling them how they made their decisions. You feel less alone."
When her own patients talk to Schaffner about mastectomy and reconstructive surgery, she sometimes unbuttons her shirt and shows them her surgery.
"That's the part that's missing, and that's what it's going to look like," she tells them.
Connecticut is one of the states that the federal government's Centers for Disease Control and Prevention (CDC) has identified as having among the highest rates of breast cancer, but Chagpar said that data must be assessed with caution. The state has legislation that requires mammography patients be told in writing if their results show they have dense breast tissue, which might obscure a cancerous tumor. Such patients can then get additional screening. The CDCs figures, in fact, reveal that Connecticut has an excellent breast cancer cure rate.
Schaffner said that people told her after her double mastectomy that she was courageous for going through with the procedure. She sees it somewhat differently.
"I don't know about courageous," she said. "I know that I really didn't want to have breast cancer."
There are many reliable web sites with information on the BRCA gene mutations. The federal government's National Cancer Institute at the National Institutes of Health maintains a comprehensive one: www.cancer.gov/cancertopics/factsheet/Risk/BRCA.