Q. Is heredity an important factor in ovarian cancer?
A. Only 5–10% of ovarian cancers are thought to occur due to a hereditary predisposition. Despite this fact, knowledge of family history is important information for both a patient and her physician because of the potential preventive and treatment options available. Hereditary predisposition is assessed through genetic counseling and, if appropriate, genetic testing.
Based on 2006 American Cancer Society estimates, more than 20,000 ovarian cancers will be diagnosed in American women. Although it is not the most common gynecologic malignancy, it is the most lethal, causing more than 15,000 deaths—more than all other cancers of the female reproductive tract combined. The overwhelming majority of these cases occur on a sporadic or random basis.
Q. How many women have a hereditary predisposition to ovarian cancer?
A. Much of the early research in this area focused on the importance of family history as a predictor of the risk of developing cancer. Over the past two decades, an enormous amount of work has refined our knowledge and has led to the discovery of mutations, or alterations, in certain genes that are responsible for the predisposition to a variety of cancers.
With regard to ovarian cancer, two syndromes account for most of the hereditary cases: the breast-ovarian syndrome, associated with mutations in the BRCA1 and BRCA2 genes, and the hereditary nonpolyposis colon cancer (HNPCC) syndrome, associated with different mutations in what are called mismatch repair genes.
BRCA gene mutations occur at a rate of about 1 in every 800 to 1,000 individuals in the general population. Certain groups have a greater incidence of BRCA mutations. Most notable among these are people of Ashkenazi Jewish descent. In this population the rate is about 1 in 50, or 2%—a marked increase over the baseline. Although a family in which many members have been affected by ovarian or breast cancer may point to the presence of a BRCA mutation and a hereditary link, there are cases in which an individual has no family history of cancer but a significant personal history that places her at considerable risk. For instance, the development of early (premenopausal) breast cancer may be the only indication of the presence of a BRCA mutation even in the absence of other family members with breast or ovarian cancer.
Q. What are the risks associated with having one of these mutations?
A. When a woman is found to have a BRCA mutation, her risk of developing ovarian cancer is far greater than that of a woman in the general population.
BRCA1 and BRCA2 mutations carry a risk of ovarian cancer of up to 45% compared with a risk of 1.4 percent in the general population. With regard to breast cancer risk, the rates are also significant, with almost 85% of women with a BRCA mutation developing cancer.
HNPCC is primarily a colon cancer syndrome, although the presence of mutations in the mismatch repair genes lead to the development of a broad spectrum of other malignancies, including cancers of the uterus, ovaries, small bowel, stomach, biliary tract, renal pelvis and ureter, and brain. Among women with the HNPCC syndrome, endometrial cancer occurs in up to 71% and ovarian cancer in about 12%.
Q. What are the options for women with mutations?
A. A woman has several options when faced with the news that she has a mutation that predisposes her to cancer.
Surveillance, or close observation, may be undertaken, usually on an every-six-months basis. At this interval a pelvic examination, a transvaginal ultrasound, and a CA125 blood test are performed. Ongoing research is seeking to develop new strategies to enhance success with early detection.
Chemoprevention focuses on the use of medications to reduce cancer risk. The birth control pill may be considered for these women, particularly when contraception is desired. Ovarian cancer risk is cut by half when the pill has been used for at least five to six years, and the protective effects last for many years after the drug has been discontinued.
Prophylactic or risk-reducing surgery (RRS), the removal of both ovaries and fallopian tubes, may be an option for some women. Risk-reducing surgery may often be accomplished through minimally invasive (laparoscopic) techniques and decreases the risk by about 95%—limited mainly by the occurrence of primary peritoneal cancer, which originates from the lining of the abdominal cavity and develops from the same tissue that gives rise to the surface of the ovary, where most cancers occur. Because of the significant incidence of uterine cancer associated with HNPCC, RRS procedures in these women must include a hysterectomy as well as the removal of the ovaries and the tubes.