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Re: [Fwd: Fw: An Important Message] - CA-125From: Richard M. Roberts (gene@vol.com)Sun Dec 6 23:31:54 1998
At Fri, 04 Dec 1998, Clifford J. Goodman, Jr., M.D. wrote: ...>Please bear with me if you've already seen this. My sister, a banker, >forwarded this to me, but I've already had patients bring it into the >office. How do listers respond to this? As a clinical geneticist, I would respond by suggesting that this unfortunate woman be referred to a board certified clinical geneticist with expertise in cancer genetics, who might be able to explain to her the risks and benefits of testing for peritoneal ovarian cancer post total hysterectomy. In an individual with no family history suggestive of BRCA 1 or 2, CA 125 testing is unfortunately too poor to be useful, and the patient needs to understand why, and to recognize that she is a victim of bad luck, not neglect of appropriate screening. With regard to the CA-125 serum tumor marker which is detected by radioimmunoassay: A significant proportion of healthy women have elevated levels, resulting in a low specificity. It is true that the levels are elevated in 80% of epithelial ovarian cancers. However, half of women with stage I cancers have normal levels. Thus, in women with no family history of breast/ovarian cancer, positive CA-125 serum tumor markers would occur so frequently that advice to have a peritoneal wash to screen for peritoneal cancer would be unacceptable. The U. of Kentucky quoted a 15% chance it will be elevated in any woman. Other centers have reported that only 15-50% of women affected with stage I ovarian cancer will have a CA-125 greater or equal to 35 micrograms per ml. It is crucial, however, to inform women who have had prophylactic oophorectomies because of identification of BRCA 1 carrier status that they remain at risk of peritoneal cancer, and should be offered CA-125 screening. As of last year, I had reveiwed the following (already out of date): As noted in the National Institutes Of Health Consensus Conference on ovarian cancer, ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. In 1994, 24,000 new cases are expected to be diagnosed, and 13,600 women will die from this cancer. The vast majority of women with ovarian cancer are diagnosed with advanced disease. Most often, women with early ovarian cancer have no symptoms. Its prevalence is 30 to 50 cases per 100,000 population. The lifetime incidence is 1:70 women. Three tests now in use as screening tests are: a) Bimanual rectovaginal pelvic examination. b) CA-125 testing. c) Transvaginal ultrasonography. A fourth, color Doppler imaging, is being investigated.
RISK OF BREAST CANCER IN BRCA-1 FAMILIES
AGE % Affected
30 3.2
40 19.1
50 50.8
60 54.2
>70 85 (Same for BRCA-2) Lifetime risk of other cancers: colorectal 4% prostate 7% ovarian 40% REF: Am J Hum Genet 56:265, 1995 NIH Recommendations for screening (1995): All women should have a comprehensive family history taken by a physician knowledgeable in the risks associated with ovarian cancer. Lifetime risk of ovarian cancer with no affected relatives is 1:70 (1.4%). With one first-degree relative with ovarian cancer, the lifetime risk is 5%. The benefits of screening a woman who has one or no first-degree relatives with ovarian cancer are as yet unproven, and the risks may outweigh the benefits. There is no current evidence to support routine screening in these women; however, participation in clinical trials is an appropriate option, and important in helping to ultimately define the potential benefits and risks of screening. A woman with one first-degree relative with ovarian cancer who is not able to be enrolled in a clinical trial nonetheless has a 5% risk; she may feel that despite the absence of prospective data, she has sufficient risk for her to be screened. This alternative opportunity should be available to the woman and her physician. With two or more first-degree relatives, a woman's lifetime risk rises to 7%. No conclusive data are available to show the screening benefits of these women; such individuals should be counseled by a qualified specialist regarding their individual risk. Women with two or more family members have a 3% chance of having hereditary ovarian cancer syndrome and should be counseled by a qualified specialist regarding their individual risk. For patients with a hereditary ovarian cancer syndrome, assuming autosomal dominant inheritance with 80% penetrance, the lifetime ovarian cancer risk is approximately 40%. No data demonstrate that screening these high-risk women reduces their mortality from ovarian cancer; however, the following are recommended: a) Annual rectovaginal pelvic examination. b) CA-125 determinations. c) Transvaginal sonography. (National Institutes Of Health Consensus Conference, Ovarian Cancer Screening, Treatment, And Follow-Up. JAMA 273:491-497, February 8, 1995) The University of Kentucky section of Gynecological Oncology Transvaginal Sonography (TVS) screening program for ovarian cancer has confirmed the results of other centers that TVS has a high sensitivity and moderate specificity for detection of stage I ovarian cancer. Their protocol is set up for screening women at or greater than 30 years of age with a positive family history of ovarian cancer and women at or greater than 50 years of age in general. CA-125 testing is also done, but they have found it to have inadequate sensitivity and poor specificity for use as a screening marker for stage I ovarian cancer.
.>From: "Sharen Goodman" <shgoodman@email.msn.com>
>To: "Clifford J. Goodman, Jr., M.D." <momdoc@home.com>
>>>>
-- Richard M. Roberts, Ph.D., M.D., FACMG Genetics and Prenatal Diagnostic Center Chattanooga, TN, 37421 423 499-4075
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