Ovarian cancer is somewhat of a mystery. We understand less about this cancer than we do about many others. Moreover, it produces few symptoms until it is advanced, and there is no effective screening test to catch it in the early stages. In more than 75% of cases, ovarian cancer has already spread beyond the ovaries when it is diagnosed.

Fortunately, it is also relatively uncommon. Experts predict 25,400 new cases in the United States for 1998 -- compared to 180,000 new cases of breast cancer over the same period. Unfortunately, approximately 14,500 women will die of the disease this year.

Risk factors
Age. One in 70 American women will develop ovarian cancer during her lifetime. The average age at diagnosis is 61, and the risk continues to increase until age 75, when it begins to taper off.
Heredity. Approximately 5-10% of ovarian cancers, including most early-onset cases, are due to inherited gene defects. Thus, having a mother, sister, or daughter with ovarian cancer raises a woman's lifetime risk from about 1.5% to an estimated 9.4%. Mutations in BRCA1 and, to a lesser extent, in BRCA2 -- genes that are also linked to breast cancer -- raise the lifetime risk of ovarian cancer to about 20%. Nonetheless, a close familial link to ovarian cancer doesn't guarantee that the mutation was passed on to any one individual. Genetic tests can reveal whether or not a woman has inherited the specific mutation that appears to be responsible within her family. Some women who learn that they have the mutation may elect to have their ovaries and fallopian tubes removed to minimize their chances of developing the cancer, though such surgery is no guarantee. Cancer based in ovarian cells could occur elsewhere in the abdomen even after the ovaries have been taken out.
Reproductive history. The number of times a woman has ovulated also appears to play a role, theoretically because it increases the number of cell divisions -- and consequently the opportunity for genetic mutations -- within the ovary. Potentially, trauma to the surface of the ovary during ovulation may also be a factor. A full-term pregnancy and lactation, on the other hand, give ovaries about a year's reprieve from ovulation. The more pregnancies a woman brings to term, the lower her risk of ovarian cancer. For the same reason, oral contraceptives -- even when taken for only a few months -- also appear to reduce ovarian-cancer risk. This summer, a multicenter report compared the outcomes of 207 women diagnosed with ovarian cancer and who carried a mutation of BRCA1 or BRCA2, and those of 161 of their sisters, of whom 53 were known to have the same mutations as their sisters. The researchers found that oral-contraceptive use lowered the risk of ovarian cancer. However, given the study's limitations, many questions remain and further research is needed to clarify the pill's effectiveness in lowering cancer risk in this group.
Fertility drugs. Some observational studies have suggested that clomiphene (Clomid and Serophene) and other agents that stimulate ovulation may be associated with increased risk of ovarian cancer. However, these findings remain controversial.
Other suspects. Several studies also suggest that two other practices -- a high-fat diet and long-term use of talcum powder on the genital region -- increase the likelihood of ovarian cancer. Researchers theorize that talc travels into the vagina, cervix, uterus, and ultimately to the ovaries, where it may prompt cellular changes and, later, cancer. These findings aren't fully understood, though, and some experts still consider them preliminary. However, because reducing one's fat intake and refraining from talc are not harmful and may even be helpful, these approaches may be worth considering.
Types of ovarian cancer
Three types of cells are involved in ovarian cancer. Epithelial-cell tumors, arising in the ovary's outer tissue layer, are by far the most common, accounting for more than 90% of cases. In women under 40, epithelial-cell cancer is rare. From then on, however, the risk rises until a woman's eighth decade.

Cancer of the germ cells, which normally develop into eggs, is uncommon, accounting for only 3% of ovarian cancers. It occurs in young women during their teens or 20s and can progress rapidly. However, germ-cell cancer is also highly sensitive to both chemotherapy and irradiation treatments and is very frequently brought into remission.

The third type derives from stromal cells, or those that make up the remaining ovarian tissue. Stromal-cell cancer is diagnosed in about 6% of cases of malignant ovarian tumors.

As an ovarian tumor grows, it extends outward, giving the ovary a bumpy texture. Ovarian cancer sheds cells like a dandelion scatters its seeds. They are released from the tumor and circulate throughout the abdomen, aided by normal contractions of the gut and rhythmic movements of the diaphragm. The cancer cells may attach to tissue surfaces, most commonly becoming affixed to the diaphragm, bowel, and omentum (a fatty tissue layer covering and padding abdominal organs). Ovarian cancer may also metastasize to the lungs, liver, bone, or brain.

There are usually no symptoms of ovarian cancer until cancerous tissue is large enough to make itself felt in the abdomen or pelvis. It then may cause cramping, discomfort, distention, or pain; diarrhea or constipation; a sense of incomplete emptying of the bowel and/or bladder; and fluid buildup (ascites) in the abdominal cavity. Some women function with mild symptoms for months; others develop a distended abdomen and ascites, for example, within a few weeks.

If a clinician suspects ovarian cancer, he or she takes a thorough history and does complete physical and pelvic exams. (Early ovarian cancer produces tissue changes so tiny that they cannot be detected manually, making the pelvic exam a poor screening tool.) The clinician may request a pelvic ultrasound, which supplies images and details about ovarian shape, size, and density. In some cases, other types of images, such as abdominal x-rays, computed tomography (CT), and magnetic resonance imaging (MRI), may be taken.

If the images indicate abnormal changes, the clinician usually refers the woman to a gynecologist or gynecologic oncologist, who will perform a complete exam and may repeat earlier tests. A laparoscopic examination may be included in the initial workup to get a better look at the ovaries.

If the tests indicate ovarian cancer or are inconclusive, the specialist may schedule exploratory surgery to inspect the ovaries and the entire abdominal cavity. (If early tests strongly suggest cancer, an exploratory may be done initially.) This procedure is often performed by a gynecologic oncologist through an incision down the middle of the abdomen, which offers better visibility than laparoscopy does. It enables the removal of visible tumors and the collection of fluid that will be tested for the presence of cancer cells. The tissues and fluid will be analyzed by a pathologist.

The pathologist will classify abnormal cells by grade: the lower the grade, the better the potential outcome. Then, the oncologist will rank ovarian cancer by stage, based on the extent of the tumor. The higher the stage, the more advanced the disease.

On average, the 5-year survival rate for ovarian cancer is about 40%. If it is discovered within the ovary (stage I), the cure rate is about 90%, which is often effected by surgery alone. If it is more advanced (stages III and IV), however, the cancer is more likely to recur, and the rate of survival 5 years after treatment is closer to 20% and 10%, respectively.

Once ovarian cancer has been diagnosed, the oncologist will request a blood test for CA 125, a protein produced by the ovaries that is usually elevated in women with ovarian cancer. CA 125 levels are routinely used as indicators of a treatment's effectiveness. However, CA 125 is not a good diagnostic test because it doesn't provide a clear signal of ovarian cancer; the protein may be elevated for various other reasons, including normal menstrual-cycle changes, benign ovarian cysts, endometriosis, pelvic inflammatory disease, or other cancers. Moreover, about half of women with early ovarian cancer have normal CA 125 levels.

The goal of the open operation is to remove as much cancer as possible. The procedure involves taking out the uterus, ovaries, and fallopian tubes. It also includes removing the omentum and growths on the diaphragm or bowel, and performing lymph-node dissection. Occasionally, part of the colon may be taken out as well. Removing as much of the tumor as possible not only improves the woman's comfort, it may render the residual cancer more accessible to chemotherapy, thereby making treatment more effective.

Chemotherapy accomplishes a complete remission about 50% of the time. It usually involves six courses of intravenous treatment, most commonly with platinum (Platinol or Paraplatin) and paclitaxel (Taxol). During this period, blood levels of CA 125 are checked. Circulating CA 125 concentrations that decline steadily and reach normal levels indicate that the treatment is doing the job. CA 125 levels that remain high, however, indicate that the cancer cells are resistant to the chemotherapy. The combination treatment may still be completed, but the woman's prognosis is more grave than if CA 125 had fallen. A host of other chemotherapy drugs, used alone or in combination, are also available.

Irradiation of the abdomen and/or pelvis may be part of therapy as well, though it is used far less commonly than chemotherapy.

Once her treatment is finished, an ovarian-cancer patient usually sees her oncologist every 3 months for 2 years. At these visits, she may have a pelvic exam, a vaginal ultrasound, and a CA 125 test. If all is clear after that time, her appointments are typically scaled back to one every 6 months.

A second surgery can help ensure that the abdominal cavity is free of cancer. However, this "second-look" procedure is generally not considered standard except during the investigation of new therapies, because there is no evidence that it actually improves survival rates.

Ongoing search
Scientists are exploring better ways to screen for, diagnose, and treat ovarian cancer. Any discussion of ovarian-cancer risk should consider a woman's age, family history, number of full-term pregnancies and lactation, and her fertility-drug and oral-contraceptive use. Women with a family history of ovarian or breast cancer may wish to speak with their clinicians about genetic testing. (See HWHW, July 1998.)

If you are at high risk of ovarian cancer or have been diagnosed with the disease, you may wish to enter an investigational trial. Doing so, you will have the standard of care that's appropriate for your particular health concerns, and you might receive something better. To learn more about these trials, contact the National Cancer Institute at 1-800-4-CANCER.

For further information
Food and Drug Administration, "Ovarian Cancer," FDA Consumer, http://www.fda.gov/opacom/catalog/ovatian.html

National Cancer Institute, Cancer Information Service, 1-800-4-CANCER, http://www.nci.nih.gov

Cancer Care, http://www.cancercare.org

Seminars in Oncology, June 1998, Volume 25, Issue 3 -- a special report on ovarian cancer

National Institutes of Health Consensus Statement, "Ovarian Cancer: Screening, Treatment, and Follor-Up," Volume 12, No. 3, April 5-7, 1994

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