HomeJune 2011Harmful Hereditary Mutations

Harmful Hereditary Mutations

Information evolving about hereditary breast and ovarian gene mutations is critically important for those potentially affected to understand.  These gene changes markedly increase the risk of breast, ovarian and other cancers.

An Ashkenazi Jewish woman in her 50’s, Rachel, is diagnosed with breast cancer.  Her mother, Sadie, had a younger sister, Zelda, who died of breast cancer in her early forties 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 determine whether they carry the hereditary ovarian and breast cancer gene mutations, 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 brothers, who have daughters in their twenties, 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 forties 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, 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.  Rachel’s nieces are able to make health choices based on this information.  They start hormonal contraceptives (HC) which lower the incidence of ovarian cancer for all women by 50 percent when taken for just four years.  The niece whose father has the harmful BRCA2 mutation plans to undergo genetic counseling and gene testing at age 25.  The niece whose father does not carry the harmful BRCA2 mutation is grateful for the knowledge that she need not worry.

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 screening regimen, including a baseline mammogram.

The BRCA1 and BRCA2 genes are involved in cell growth control mechanisms.  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.

BRCA alterations can be found in all ethnic populations.  Groups founded by a small number of ancestors, such as Ashkenazi Jews, French Canadians, Dutch and Icelanders may carry specific “founder” gene changes (mutations).  Ashkenazi Jews have a 10-fold increase in the frequency of these gene mutations.

Breast cancer occurs in 12 percent of the general population.  Women with the highest risk variants of BRCA1 or BRCA2 mutations have a theoretical breast cancer risk of 50 to 87 percent.  Ovarian cancer occurs in 1.4 percent of the general population and 15 to 40 percent of women with a harmful BRCA mutation.

Other malignancies associated with the harmful BRCA genes, which can occur in either sex, include cancers of the pancreas, stomach, gallbladder and bile duct, as well as melanoma.

Men with these genes changes have an increased risk of breast cancer and early-onset prostate cancer.  Many of these cancers will develop at an earlier age than expected.

Jeanne Homer, board-certified genetic counselor explains, “There is a 50 percent chance that either a mother or a father carrying a harmful BRCA gene change can pass it to his or her offspring.”  Since the gene mutation is dominant, the risks described above can be inherited from a single parent.

Gene testing for BRCA mutations can be performed on blood or 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.  In a family with 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 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 change.   Genetic testing is relevant for both males and females, not only for their own risk, but for the potential transmission down through the generations.

The Genetic Information Non-Discrimination Act, GINA, 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.

Surveillance strategies for breast cancer, such as breast surgeon consultation for exams and breast magnetic resonance imaging, along with routine mammography, are recommended.  Ovarian cancer surveillance is minimally effective.

Use of medications can prevent cancer.  HC use reduces the risk of ovarian cancer in all women, even those with a harmful BRCA mutation, by fifty percent when used for four 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.  Breast cancer risk can be reduced with use of Tamoxifen or Evista.

Surgery reduces the risk of both breast and ovarian cancer when a woman is positive for a harmful BRCA gene change.  Risk-reduction bilateral mastectomy is associated with a marked decrease in breast cancer.  Removal of the ovaries and fallopian tubes is a consideration by age 35, or when child-bearing is complete.  These strategies have been shown to reduce overall mortality by 76 percent.

Supplemental cancer insurance is available for people at higher risk of cancer who currently have health insurance.  It will protect against 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 5 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 and prolong life.  Protection from discrimination based on genetic information exists for health insurance and employment.

Knowledge about genetic risk empowers people to live longer, healthier lives.


Genetic Testing for Breast and Ovarian Cancer Risk:  It’s your choice.  National Cancer Institute: http://www.cancer.gov/cancer topics/Genetic-Testing-for-Breast-and-Ovarian-Cancer-Risk

Dr. Jane K. Bening is a board-certified gynecologist in private practice in Newport Beach.  She can be reached at (949) 720-0206.

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