Cancer News in Context is excited to publish four posts this week on high-risk breast and ovarian cancer. These posts will provide insight for women (and their families) from Washington University School of Medicine physicians on unique aspects of high-risk disease — from genetic testing and treatment to prevention and risk management.
July 11 – Overview: High-Risk Breast Cancer – Prevention and Risk Management
July 12 – High-Risk Ovarian Cancer: Identifying, Preventing, and Managing Risk
July 13 – Treating and Managing Future Risk in Women with Hereditary Breast Cancer
July 14 – Genetic Risk of Breast Cancer and Your Options
David Mutch, MD
Ira C. and Judith Gall Professor of Obstetrics and Gynecology, Division of Gynecology Oncology, Washington University School of Medicine
Cancer is a disease caused by a series of mutations in our DNA. This is true for ovarian cancer, the most lethal of all the gynecologic cancers. Like breast cancer, a predisposition of this disease can be inherited through inherited mutations in genes that are responsible for DNA repair. If one cannot repair DNA damage that occurs in the process of daily living then errors can accumulate in our DNA eventually leading to loss of normal cellular control. Known genes that are associated with inherited predisposition of ovarian cancer are the BRCA1 or BRCA2 genes and genes called mismatch repair genes (MLH1, MSH2, MSH6 or PMS2). These genes are all responsible for DNA repair so when they do not function properly DNA mutations accumulate in a more rapid manner than in a person without this defect.
Over five percent of the general population has a DNA abnormality that predisposes them to ovarian cancer. The lifetime risk of developing ovarian cancer if one inherits a mutation in one of these genes is over 50 percent. There is a great deal of data that suggests that if a woman has her ovaries removed in this setting, that one can nearly completely prevent ovarian cancer from developing. Oral contraceptives may also decrease the risk of developing ovarian cancer by 50 percent and therefore may be a good temporizing tool in young women. . The difficulty lies in determining who has a mutation in one of these genes and is therefore at high risk for developing ovarian cancer and will therefore benefit from intervention. Now that we can sequence an individuals DNA we can easily determine those at high risk but we need to know who to test.
Breast and ovarian cancer are linked and those who develop breast cancer are also at risk for ovarian cancer and visa versa. There are certain populations of individuals who are at high risk for having a mutation and can help us learn who should be counseled and tested.
Factors That Should be Considered When Considering Referring a Patient for Genetic Counseling for Risk Assessment of Familial Breast or Ovarian Cancer
- Breast Cancer at younger than 40
- Family member with a male breast cancer
- Premenopausal breast cancer and a first- or second-degree relative with breast or ovarian cancer or two relatives of any degree or age
- Breast cancer or ovarian cancer in a family of Ashkenazi Jewish heritage
- High-grade papillary serous carcinoma of the ovary, fallopian tube or primary peritoneal cancer at any age
- Two primary cancers of the breast or breast and ovary at any age
- A known mutation within the family
- Bilateral breast cancer
Note: Peritoneal and fallopian tube cancers should be considered as part of the spectrum of the Hereditary Breast and Ovarian Cancer Syndrome. Close relative is defined as a first, second or third degree relative (ie mother, sister, daughter, aunt, niece, grandmother, granddaughter, first cousin, great grandmother, great aunt)
We believe that all people who are going to undergo testing should be counseled first and then undergo continuous counseling until they decide on treatment. Furthermore we believe that an affected individual within the family should be tested first. If there is a mutation then everyone who undergoes counseling and testing in that family can undergo testing for just that mutation. Furthermore, this is a dynamic situation, and we are now testing for many other genes than just BRCA1 or 2. Because of the development of new technology we can test many genes for the same or less cost than testing for a mutation in the BRCA genes a few years ago. These “panels” of genes are expanding and it is important for the genetic counselor to keep up with the patients so that they can be make aware of new developments.
Furthermore, formal hereditary cancer risk assessment should include review of at least a 3-generation pedigree, including first-degree, second-degree, and third-degree (cousins) relatives from both maternal and paternal families. Occasionally, expansion of the pedigree beyond these relatives may reveal important information that will guide recommendations for genetic testing and medical management.
The process of helping people understand and adapt to medical, psychological and familial implications of genetic contributions to disease. This process integrates the following: interpretation of family and medical histories to assess the chance of disease occurrence or recurrence; education about inheritance, testing, management, prevention, resources and research; counseling to promote informed choices and adaptation to the risk or condition.
Once risk has been determined then the patient can decide with the help of the health care professional how to proceed with the results. Prophylactic surgery, while the most effect preventive treatment may not be appropriate in young women who wish childbearing. The role of the genetic counselor and physician is to work together to develop the best treatment strategy for each patient and family member.