Hereditary cancer syndromes play an important role in women’s health. The leading female cancers — breast, uterus, ovary, cervix and vulva — are all affected by hereditary syndromes. Genetic testing and risk reduction strategies dramatically improve patient care and outcomes.
“Every woman is at risk for these cancers,” said Susan C. Modesitt, MD, Richard and Louise Crockett professor of OB/GYN, director of Gynecologic Cancer and co-director of the High Risk Breast Cancer and Ovarian Cancer Clinic at the University of Virginia Health System. “But hereditary syndromes increase that risk dramatically. We all have a one in three or four chance of ovarian cancer, for example, but your relative risk can jump 35-fold with the BRCA1 or BRCA2 gene. A BCRA mutation gives you an 85 percent lifetime risk for breast cancer. Anything we can do to identify and reduce those risks is a positive step. Something as simple as birth control pills can cut a woman’s risk of ovarian cancer in half.”
Dr. Modesitt discussed the more common hereditary cancer syndromes in women during a clinical symposium on Sunday morning. While the range and accuracy of genetic testing continues to improve, clinical clues are the first steps in almost every diagnosis.
An early cancer diagnosis suggests heredity at work, she said. So does the occurrence of related cancers in two or more family members on the same side.
Specific combinations of cancers also suggest heredity. Breast and ovarian cancer share BRCA gene mutations. Endometrial, colon and ovarian cancers as well as breast, endometrial and thyroid cancers share common mutations.
Multiple rare cancers are another clue. So are multiple primary cancers in the same individual.
BRCA 1 and BRCA 2 and related genes are the most common hereditary links, followed by Lynch syndrome (also known as HNPCC), Peutz-Jeghers syndrome (STK-11), Li-Fraumeni (P53) and Cowden’s syndrome (PTEN).
The role of hereditary syndromes varies by cancer type. Between 10 and 20 percent of ovarian cancers have a hereditary component. BRCA 1 and BRCA 2 account for about 90 percent of the hereditary component, followed by Lynch syndrome and other single gene mutations.
Between seven and ten percent of breast cancers are hereditary. BRCA 1 and BRCA 2 account for between 50 and 70 percent of hereditary breast cancers. Another 45 to 50 percent are the result of unknown genes with the balance divided between PTEN/P53, ATM/CHEK2 and DNA repair mutations such as PALB2.
All of these genes, and others, can be detected by genetic screening.
“Genetic screening can tell me exactly how to treat a particular patient,” Dr. Modesitt said. “A negative test may be non-informative. It doesn’t clear the patient of all risks, just the genetic risks you screened for.”
Most insurance carriers now cover genetic screening, she said, but coverage for genetic counseling is spotty.
A positive genetic test opens three strategies: screening, chemoprevention and surgical risk reduction. Screening can be effective for breast and colon cancer, less so for ovarian and endometrial cancer.
Chemoprevention can significantly reduce risks, depending on the cancer. Tamoxifen can cut the risk of breast cancer in half, but aromatase inhibitors are not currently recommended outside clinical trials. Growing evidence suggests that aspirin can reduce the risk of colon and other cancers.
Prophylactic mastectomy can reduce the risk of breast cancer. Prophylactic salpingo-oophrectomy can be even more useful, reducing the risk of ovarian and breast cancer.
“I have a ‘no ovary left behind’ policy,” Dr. Modesitt said, “but I do not have a ‘no breast left behind’ policy. And don’t forget the non-gynecological cancers — colon, gastric, melanoma, pancreatic, renal — that you may not ordinarily think about.”