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Are There Any Good Tests for Ovarian Cancer?

IS PELVIC ULTRASOUND A GOOD SCREENING TEST FOR OVARIAN CANCER?
Unfortunately, the answer is no. Pelvic ultrasound, or sonography, is a medical test that uses sound waves bounced off the ovaries to form a picture on a screen, much like the technology used for ship's sonar. This technique was felt to be a promising method to detect growth in the ovaries that might be the beginning of a cancer. The hope was that this test would detect ovarian cancer before it had a chance to spread. Unfortunately, the test has a hard time distinguishing ovarian cancer from other cysts on the ovaries, which are almost always benign. These benign cysts are much more common than ovarian cancer, and most of them do not need to be treated at all. (Please visit http://www.parkermd.com/ovarian-cysts.htm for more information on ovarian cysts and pelvic ultrasound)

A study that illustrates this problem was conducted in England where an ad was placed in the paper for free ovarian cancer screening. Within a short period of time, 5700 women readily agreed to get this free testing. Of the 5700 women who had a sonogram of their ovaries performed, 361 of them had abnormal appearing ovaries. All 361 of these women then underwent major abdominal surgery. Three of these women were found to have widely spread ovarian cancer that would have been easily detected by a pelvic exam. And only three women with early ovarian cancer were found and cured.

This was wonderful for the three women whose lives were saved by the sonogram. However, 355 women had a major surgery that they did not need. They were subjected to the risks of anesthesia, bleeding, need for transfusion, infection, and injury, in addition to the discomfort of surgery and the time needed for recovery. At this point for the general population, the risk that an abnormal screening sonogram may lead to unnecessary surgery seems to outweigh the benefit.

In addition, it has been calculated that if all 43 million American women over the age of 50 had a pelvic ultrasound every year, we might expect 2.5 million women to have an abnormality found. Thirty-seven thousand of these women would be found to have ovarian cancer that would otherwise have not been detected so early. But, 2,463,000 women would have had unnecessary surgery. Of those women, 2,500 might be expected to die from the procedure, and 112,500 would have a serious complication. In addition, the cost of the ultrasounds would be $11.8 billion per year. The cost of the unnecessary surgeries would be about $ 37.5 billion per year. So for all these reasons, a sonogram is not recommended as a routine screening test for ovarian cancer.

IS CA-125 A GOOD SCREENING TEST FOR OVARIAN CANCER?
Cancer cells are different than normal cells, and they produce bio-chemicals that differ from those produced by normal cells. One of these bio-chemicals has been detected in the blood stream of women with ovarian cancer to a much greater degree than in normal women. The blood test to detect this chemical is called CA-125.

However, as with ultrasounds, the CA-125 test can indicate cancer in normal women who do not have ovarian cancer. For women who are postmenopausal, ovarian cancer will only be found in about 5% of women with an elevated CA-125 level. The test is even less accurate in women who have not yet reached menopause. Conditions common in young women - endometriosis, fibroids, ovarian cysts, pelvic infections, pregnancy, normal menstrual periods - can all make the level of CA-125 go up in the absence of cancer. In addition, the test can be elevated in entirely healthy women of any age for no apparent reason.

Therefore, it is not a good idea to perform this test on women in an effort to detect ovarian cancer. If abnormal, the result usually scares the patient. The doctor, also worried about the possibility of ovarian cancer will, more often than not, recommend surgery that is likely to be unnecessary. Also, CA-125 levels are normal in 50% of women who do have early ovarian cancer, just the women we would like to find in order to treat them when the disease is curable. Therefore, we do not recommend CA-125 as a screening test for women at average risk of getting ovarian cancer.

DO SCREENING TESTS MAKE SENSE IF YOU ARE AT VERY HIGH RISK FOR DEVELOPING OVARIAN CANCER?
Possibly. If you have a very strong family history of ovarian cancer, the goal must be early detection. For those few women who have a 10-50 times greater risk of developing ovarian cancer, it is probably worth the risk of having a falsely abnormal test result, even if it leads to unnecessary surgery. A number of medical programs have been established to test high-risk women with sonograms and CA-125 levels in an attempt to detect ovarian cancer at an early and curable stage and collect information about the effectiveness of these tests. If you are at high risk, you might ask your doctor if a program exists nearby. To date, these programs have found only a few early, curable ovarian cancers. In addition, a number of women have had normal screening tests, but go on to develop ovarian cancer within the next 6 months, before they are due to be tested again. However, this approach is new, and w e hope as information continues to be gathered, some new methods will be developed that can lead to early ovarian cancer detection. As noted below, women who are at very high risk might consider the removal of their ovaries.

SHOULD YOU GET GENETIC TESTING FOR OVARIAN CANCER?
Some women with a strong family history for ovarian cancer have been found to have a mutation in a gene called BRCA, which stands for BReast CAncer gene. In addition to inheriting a higher risk of getting breast cancer, women with this mutation have a higher risk of developing ovarian cancer. In the general population this mutation occurs in about 1 out of 1,000 women. However, in women of eastern European Jewish descent the mutated gene occurs in 20 out of 1,000 women. Women who have a BRCA mutation have a 25-50% chance of developing ovarian cancer in their lifetimes, compared to the 1% risk for women who do not have the mutation. Interestingly, women who have this gene mutation and develop ovarian cancer develop a less aggressive cancer and survive longer than women who do not have this mutation. As is true for the non-genetic form of ovarian cancer, taking birth control pills substantially reduces the risk of inherited ovarian cancer.

Testing for this gene is now available for women who suspect they are at high risk because of a family history of ovarian cancer. Deciding whether to be tested is often a difficult decision. There are a number of reasons you might consider getting the test. If it is negative, then neither you nor your daughters need to be concerned about an increased risk of this disease. This often lifts an enormous burden of worry. If the test is positive, then you will have some decisions to consider. With an increased risk of ovarian cancer (and an increased risk of breast cancer), the available options to decrease this risk are drastic; removal of your ovaries and/or breasts (mastectomy). Removal of your ovaries will eliminate your risk of ovarian cancer but does involve a surgical procedure. Removal of ovaries can now be performed with laparoscopic surgery as an outpatient, but general anesthesia is necessary and, as is true with all surgery, includes some risk. In addition, removal of the ovaries will not prevent a very rare form of inherited cancer that affects the inside lining of your abdomen called the peritoneum. In that this gene mutation also increases your risk of breast cancer you will need to address the issue of removal of your breasts, mastectomy, for preventative reasons. Your age, childbearing issues, your feelings about the possibility of cancer, and your feelings about surgery and removal of feminine parts of your body are all important issues. These are extremely difficult decisions and are best made with the counseling and advice of a trained genetic counselor. It is important to see the genetic counselor before you get tested, so that these issues can be discussed in advance of the results. Ask your doctor to recommend someone to you or call a nearby medical center for a referral.

Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutations: a decision analysis.
Katrina Armstrong, J. Sanford Schwartz, Thomas Randall, Stephen C. Rubin, Barbara Weber

Purpose : The decision about prophylactic oophorectomy is difficult for many premenopausal women with BRCA1/2 mutations because of concerns and controversy about the use of hormone replacement therapy (HRT) after oophorectomy.

Methods : A Markov decision analytic model used the most current epidemiologic data to assess the expected outcomes of prophylactic oophorectomy with or without HRT (to age 50 years or for life) in cohorts of women with BRCA1/2 mutations. Sensitivity analyses were conducted to assess the impact of alternative assumptions about effects of HRT, effects of prophylactic oophorectomy, and risks of cancer associated with BRCA1/2 mutations.

Results : In our model, prophylactic oophorectomy lengthened life expectancy in women with BRCA1/2 mutations, irrespective of whether HRT was used after oophorectomy. This gain ranged from 3.34 to 4.65 years, depending on age at oophorectomy. Use of HRT after oophorectomy was associated with relatively small changes in life expectancy (+0.17 to -0.34 years) when HRT was stopped at age 50, but larger decrements in life expectancy if HRT was continued for life (-0.79 to -1.09 years). HRT was associated with a gain in life expectancy of between 0.39 and 0.79 years for mutation carriers undergoing both prophylactic mastectomy and oophorectomy.

Conclusion : On the basis of the results of this decision analysis, we recommend that women with BRCA1/2 mutations undergo prophylactic oophorectomy after completion of childbearing, decide about short-term HRT after oophorectomy based largely on quality-of-life issues rather than life expectancy, and, if using HRT, consider discontinuing treatment at the time of expected natural menopause, approximately age 50 years.

Despite the limitations inherent in modeling, this study provides important information for women with BRCA1/2 mutations. For these women, premenopausal oophorectomy was associated with a substantial increase in life expectancy, irrespective of the decision about subsequent HRT. Furthermore, the risks and benefits of HRT until age 50 were closely balanced in these women, making the overall impact of HRT on life expectancy relatively small. However, on the basis of recent data from the WHI, long-term continuation of HRT beyond age 50 was associated with a significant decrement in life expectancy. Thus, we believe that all women with BRCA1/2 mutations should be strongly encouraged to undergo prophylactic oophorectomy after completion of childbearing, should decide about the use of short-term HRT after oophorectomy on the basis of quality-of-life issues and, if they choose to take HRT, should plan to discontinue its use at or before the expected age of natural menopause.

ARE THERE ANY NEW SCREENING TESTS ON THE HORIZON?
There is an enormous amount of money being spent on ovarian cancer research and much of it is aimed at tests for early detection. The most recent and interesting of these developments is called proteomics. Researchers took blood samples from women with ovarian cancer and compared all the proteins present in their blood to the blood samples from women without ovarian cancer. Using complicated computer analysis, they were able to detect a group of proteins in the women with cancer that were not present in the cancer-free women. Despite not knowing what proteins they had found or what their function was, they were able to determine a pattern of proteins that was consistently found in women with cancer. This pattern of proteins was then checked against stored blood samples from another group of women. Half of these women had surgery for ovarian cancer, and the other half were cancer-free. The researchers were not made aware of which blood samples came from which women. All women (100%) with cancer were accurately detected by the test. Importantly, all (100%) women with early, curable ovarian cancer had an abnormal test result. And, 95% of women without ovarian cancer had a normal test. While this technology is still in its infancy, it appears that this kind of analysis appears promising for the early detection of ovarian cancer. If the test continues to be successful, it will probably be available to the public in the next few years.

Although early studies of proteomics were extremely encouraging, as seen below, newer studies have not been quite as accurate. Therefore, the FDA is requiring further testing before allowing the release of this new technology for use by the general public. Hopefully, researchers will be able to modify the test so that it is accurate enough to use and we will let you know as soon as the test becomes available.

Use of proteomic patterns in serum to identify ovarian cancer.
Lancet. 2002 Feb 16;359(9306):572-7.
Authors: Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA.

BACKGROUND: New technologies for the detection of early-stage ovarian cancer are urgently needed. Pathological changes within an organ might be reflected in proteomic patterns in serum. We developed a bioinformatics tool and used it to identify proteomic patterns in serum that distinguish neoplastic from non-neoplastic disease within the ovary. METHODS: Proteomic spectra were generated by mass spectroscopy (surface-enhanced laser desorption and ionisation). A preliminary "training" set of spectra derived from analysis of serum from 50 unaffected women and 50 patients with ovarian cancer were analysed by an iterative searching algorithm that identified a proteomic pattern that completely discriminated cancer from non-cancer. The discovered pattern was then used to classify an independent set of 116 masked serum samples: 50 from women with ovarian cancer, and 66 from unaffected women or those with non-malignant disorders. FINDINGS: The algorithm identified a cluster pattern that, in the training set, completely segregated cancer from non-cancer. The discriminatory pattern correctly identified all 50 ovarian cancer cases in the masked set, including all 18 stage I cases. Of the 66 cases of non-malignant disease, 63 were recognised as not cancer. This result yielded a sensitivity of 100% (95% CI 93--100), specificity of 95% (87--99), and positive predictive value of 94% (84--99). INTERPRETATION: These findings justify a prospective population-based assessment of proteomic pattern technology as a screening tool for all stages of ovarian cancer in high-risk and general populations.

 

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