An Ashkenazi Jewish woman in her 50s, Rachel, is diagnosed with breast cancer. Her mother, Sadie, age 80, has a history of melanoma, which was treated successfully. Sadie's younger sister, Zelda, died of breast cancer in her early 40s many years ago. Zelda had two daughters who live far away, with whom they have lost contact. Rachel's father and his family have no history of cancer.
An astute clinician recommends genetic counseling for Rachel and Sadie to estimate their risk of carrying the hereditary ovarian and breast cancer gene mutations for BRCA1 and BRCA2. While Sadie has no interest in being tested, Rachel is found to have the harmful BRCA2 gene change. She informs her immediate family, her parents and her two brothers, of this finding. Her brothers, who have daughters in their 20s, are entirely disinterested, having no knowledge of the ramifications of this information and no personal history of cancer.
Rachel finds her long-lost cousins, Zelda's daughters, who are in their 40s with no history of cancer. She urges them to get genetic counseling, as there is a high probability that their mother had a BRCA gene mutation.
After soul searching and multiple medical and psychological consultations, Rachel undergoes double mastectomies, a hysterectomy and removal of both tubes and ovaries.
While recovering from surgery and starting chemotherapy for her breast cancer, she summons the strength to explain to her brother's daughters, her nieces, their risk of carrying a BRCA gene mutation. Meanwhile her cousins, Zelda's daughters, have happily reentered her life, grateful for the family genetic information. One cousin is positive for the BRCA gene mutation as well, and opts for the same prophylactic surgery as Rachel.
Eventually, with pressure from a doctor friend and Rachel's nieces, her brothers undergo genetic counseling and gene testing. One is positive for the BRCA2 gene mutation and one is negative. This is consistent with the 50% chance that any child can inherit a BRCA gene mutation from a parent who carries it.
These gene mutations have a dominant expression. Rachel's nieces are able to make health choices based on this information. They start hormonal contraceptives, which lower the incidence of ovarian cancer for all women by 50% when taken for just four years. The niece whose father is BRCA2 positive plans to undergo genetic counseling and gene testing at age 25. The niece whose father is BRCA2 negative is grateful for the knowledge that she need not worry about being a BRCA gene mutation carrier.
Rachel's brother who has the BRCA2 gene mutation learns that he is at greater risk for early prostate cancer, melanoma, breast cancer and other cancers. His personal physician is able to institute a vigilant screening regimen based on this knowledge.
What are BRCA1 and BRCA2 genes?
These genes are involved in cell growth control mechanisms associated with the development of hereditary breast and ovarian cancer. The name stands for breast cancer susceptibility. An inherited change in an individual's BRCA1or BRCA2 gene can be the first step toward uncontrolled tumor cell growth.
What populations are at risk to carry these genes?
BRCA alterations can be found in all ethnic populations. Groups founded by a small number of ancestors, such as Ashkenazi (Eastern European) Jews, French Canadians, Norwegians, Dutch and Icelanders may carry specific "founder" gene changes (mutations). Ashkenazi Jews have a 10-fold increase in the frequency of these genes.
What are the effects of the BRCA1 and BRCA2 gene mutations?
Breast cancer occurs in 12% of the general population compared to 50% to 87% of women with a harmful BRCA mutation.
Ovarian cancer occurs in 1.4% of the general population and 15% to 40% of women with a harmful BRCA mutation. Fallopian tube and abdominal (peritoneal) cancers, which are more frequent with BRCA gene changes, are included in this group.
Other malignancies associated with the harmful BRCA genes, which can occur in either sex, include cancers of the pancreas, stomach, gallbladder, and bile duct and melanoma.
Men with these genes changes have a large increase in breast cancer, as well as early onset prostate cancer.
Many of these cancers will develop at an earlier age than expected.
How are the BRCA gene mutations inherited?
Jeanne Homer, board-certified genetic counselor and supervisor of the Hereditary Cancer Program at Hoag Hospital in Newport Beach, explains, "There is a 50% chance that either a mother or a father carrying a harmful BRCA gene can pass it to their offspring."
Since the gene is dominant, this means that the risks described above can be passed equally from either parent.
How are the BRCA gene mutations detected?
Gene testing for BRCA mutations can be performed on blood, and now also on saliva. Experts strongly recommend genetic counseling with a certified professional, to estimate benefits and risks of knowledge of gene status, prior to initiating the test.
According to Jeanne Homer, genetic counselor, "People tested prior to 2006 with a surprising negative result should consider retesting due to improved sensitivity."
Who should consider BRCA gene testing?
In a family with a history of breast and/or ovarian cancer, it is most informative to first test a person affected with the disease.
For people not of Ashkenazi Jewish descent, familial patterns with risk for these gene mutations involve multiple cases of breast cancer in very close relatives, especially when occurring under age 50, or in both breasts. Ovarian and breast cancer among close relatives, or diagnosed together in one person, are indications for testing, as is male breast cancer.
For Ashkenazi Jews, having a very close relative with breast or ovarian cancer and other relatives on the same side of the family with breast or ovarian cancer indicates risk. In addition, an Ashkenazi Jewish woman who has had breast or ovarian cancer at any age is a candidate for BRCA gene testing.
Any person with a first-degree relative (parent, sibling or child) with a known BRCA mutation is at risk to have the gene. Genetic testing is relevant for both males and females, not only for their own risk, but for the potential transmission down through the generations.
What is the potential for discrimination based on gene status?
GINA (The Genetic Information Non-Discrimination Act) was passed in 2008. It protects U.S. citizens against bias based on their genetic information in the realms of health insurance and employment. The law does not cover life, disability, or long-term care insurance and excludes military personnel.
A genetic counselor can address individual concerns with current updates.
When the harmful genes are present, what can be done to reduce the cancer risk?
Surveillance strategies for breast cancer, such as breast surgery consultation for exams and breast magnetic resonance imaging, along with routine mammography, are recommended. Generally, ovarian cancer surveillance is minimally effective.
Use of medications can prevent cancer. Hormonal contraceptives reduce the risk of ovarian cancer in all women, even those with a harmful BRCA mutation, by fifty percent when used for longer duration (three to six years). Since this cancer is highly aggressive, the dramatic risk reduction may overshadow theoretical concerns about breast cancer risk in young woman who have the BRCA gene mutations. Further research is warranted.
Breast cancer risk can be reduced with use of Tamoxifen or Evista.
Surgery is a consideration in reduction of both breast and ovarian cancer when a woman is positive for a harmful BRCA gene. Risk-reduction bilateral mastectomy is associated with a marked reduction in breast cancer rates. Removal of the ovaries and fallopian tubes is a consideration by age 40, or when child-bearing is complete. This reduces the risk of both breast and ovarian cancers, and has been shown to reduce overall mortality by 76%.
What about supplemental cancer insurance?
This is a consideration for people at higher risk of cancer who currently have health insurance. It will protect people from severe financial losses, covering medical and non-medical expenses. Individual and family plans are available. It must be in place before an individual is 65. Persons with a history of cancer need to be cancer-free for five years to be eligible.
People at risk for carrying harmful BRCA gene mutations are advised to seek qualified genetic counseling. Gene testing involves examination of saliva or blood. Surveillance, cancer-preventing medications, and surgery are available to reduce the risk of cancer. Protection from discrimination based on genetic information exists for health insurance and employment.
Knowledge about genetic risk empowers people to live longer, healthier lives.
DR. JANE BENING is a board-certified gynecologist in private practice in Newport Beach. She can be reached at firstname.lastname@example.org.