The numbers and letters are indelibly etched on Nancy Mann's mind. They roll off her tongue as readily as Social Security numbers are recalled by most people. Their order is critical. Together they represent a part of Mann that she has carried with her since birth but only three years ago discovered. Knowing of their existence and meaning has changed her life, complicating it in some ways, freeing it in others.
“That is the mutation I have,” the IPFW dental education professor says, referring to something awry in her BRCA1 gene. BRCA1 and BRCA2 are the two human genes most commonly involved with hereditary breast cancer.
We all have these genes, even men, but a mutation in them significantly raises one's risk of breast cancer and ovarian cancer.
A woman in general has about a 12 percent risk of developing breast cancer in her lifetime, says Melissa Dempsey, genetics counselor with Parkview Comprehensive Cancer Center. If a woman has a mutation in the BRCA1 or 2 gene, she has a 50 to 70 percent risk of developing breast cancer and a 10 to 40 percent risk of developing ovarian cancer, Dempsey says.
BRCA1 and BRCA2 are tumor-suppressive, or surveillance, genes.
“When a portion of the gene has a mutation, it renders it non-functional. Its ability to do surveillance is thwarted,” said oncologist Dr. David Zimmerman with Fort Wayne Medical Oncology and Hematology.
BRCA1 mutation is especially concerning because women with it tend to develop cancer at younger ages and their tumors are more difficult to treat than those in women with a BRCA2 mutation. A BRCA1 mutation is correlated with higher risk of ovarian cancer.
Other kinds of cancers are also associated with BRCA1 and 2 mutations, including pancreatic, prostate and male breast cancer. At least 17 genes are known to have some correlation with breast cancer, Dempsey said, with about 40 genes known today to be associated with other kinds of cancers.
Genetic counseling and testing for cancer, for neurodegenerative diseases such as muscular dystrophy and Alzheimer's and many other conditions is shedding new light on what the future may hold for an individual or for the generations to come in a family. For some, the best-case scenario such testing affords is the gift of time to prepare for the inevitable. In other cases, test results lead to early treatment or even preventive measures.
That was the driving force for actress Angelina Jolie to have genetic testing and subsequent removal of both her breasts. In her May 14 New York Times op-ed piece, Jolie shared with the world why she chose to have a double mastectomy to prevent breast cancer followed by breast reconstruction.
Like Mann, Jolie has a BRCA1 mutation, and her mother died of ovarian cancer at age 56. Jolie said the preventive mastectomy has reduced her risk of developing breast cancer from 87 percent to below 5 percent.
As a genetics counselor, Dempsey helps individuals and families create a family medical “pedigree.” By identifying the side of the family and specific individuals with diseases or conditions known to have a hereditary link, Dempsey gathers information that helps her assess risk for developing the condition among other family members.
Erroneous thinking continues about how hereditary breast cancer is passed down through a family, Dempsey says, even among healthcare providers. Women are often told any breast cancer on the father's side, such as in the paternal grandmother, is irrelevant. Not so, says Dempsey. Humans get one copy of genes from their mother and the other copy from their father. Also, because a correlation exists between prostate and breast cancer, a history of prostate cancer on the father's side could also be the link to a daughter's breast cancer. A BRCA1 or 2 mutation could come from the father.
Cost for the first person in the family to have testing for BRCA 1 and 2 mutation has been running about $4,000, although Dempsey says in her nine years of experience as a genetics counselor, she has found most insurance companies cover counseling and testing for the individual diagnosed with cancer though less often for at-risk family members. For some families, the counseling process results in no need for testing and in eased minds.
“Certain people should get genetic testing, but the group who should get genetic counseling is bigger,” Dempsey says.Younger, premenopausal women who develop breast cancer should get tested for BRCA1 and BRCA2 mutation, Zimmerman said. Other red flags such as any two close blood relatives who develop breast cancer spur him to order a blood test for BRCA1 and 2 mutations and to refer to Dempsey for counseling.
Though only about 5 to 10 percent of breast cancers are due to BRCA1 or 2 mutations, about 15 to 25 percent of women are getting tested, Zimmerman said, noting more patients are asking for genetic counseling and testing. The National Comprehensive Cancer Network sets and updates criteria for who should be tested. Sometimes Zimmerman follows his gut, even if a patient doesn't meet testing criteria.
That was the case with Mann. With no family history of breast cancer, she seemed at very low risk for a BRCA1 or 2 mutation when in 2006, at age 52, she developed invasive ductal carcinoma in one breast. The cancer started in a milk duct but spread to other parts of the breast and into one lymph node. No genetic testing was recommended. Then four years later Mann developed ovarian cancer, and Zimmerman recommended genetic testing. She tested positive for BRCA1 mutation.
“He told me later, 'I never thought in 100 years you were BRCA positive,' “ Mann recalls. In addition to a hysterectomy and removal of the breast in which the lumpectomy for cancer was done, Mann chose to have her healthy breast removed as a preventive measure. “It was tough,” she says “but I have no regrets.”
Who needs testing?Who should have genetic counseling and consider genetic testing for hereditary breast cancer?
•A woman age 50 or younger who has been diagnosed with breast cancer.
•A woman of any age of has had ovarian cancer or who has a first-degree* relative diagnosed with ovarian cancer.
•Multiple breast or ovarian cancers (primary cancer) in a woman or a first degree relative.
•Any individual with multiple family members with breast or ovarian cancer.
•Any male with diagnosed breast cancer or individuals, male or female, with a family history of male breast cancer.
•An individual with triple negative breast cancer at age 60 or younger; triple negative means the cancer cells lack certain biomarkers that make the cells responsive to treatment.
•An individual of Ashkenazi Jewish heritage.
*First-degree relatives include parents, siblings and children.
Sources: National Comprehensive Cancer Network; and Melissa Dempsey, genetics counselor, Parkview Comprehensive Cancer Center
Test costs coming down
As a result of the U.S. Supreme Court's June ruling that no company or lab can “own” a human gene, the cost for BRCA1 and 2 testing has dropped from about $4,000 to under $2,500. Until this landmark decision, Myriad Genetics of Salt Lake City, Utah, held the patents on the genes, so it also had the patent for the diagnostic test used to analyze the genes for mutations. A growing number of companies are now offering a better price.
While that is good news overall for people seeking genetic testing for the mutations, Parkview genetics counselor Melissa Dempsey warns consumers to steer clear of labs with cut-rate prices of a few hundred dollars. Direct-to-consumer advertising for genetic testing, particularly via the Internet, is a growing business. The going rate for BRCA1 and 2 testing, Dempsey says, should be at least $1,000 to $2,000 for the first family member identified as at-risk for an inherited form of breast cancer. Subsequent family members' testing is less costly because the entire gene does not need analyzed.
“A gene is like a long novel. We have to read it like a book, from beginning to end,” Dempsey says. During counseling, Dempsey identifies a family member with cancer who is at risk for a mutation.
For someone with a possible BRCA1 or 2 mutation, the “whole book” of those genes is read. The mutation may be found in Chapter 13, Page 22, Line 3 of Paragraph 4. After the mutation is located in that first family member, gene analysis of relatives requires looking only at the specific gene “paragraph.”
Insurance companies may deny genetic testing for family members without cancer but who are deemed at risk, but cost for the more limited testing is only about $400.