Women's Health Articles - Cancer and Pelvic Masses

Family History Important for Ovarian Cancer Risk

Frederick R. Jelovsek MD

Do you have a family history of ovarian cancer? Is a family history of breast, colon or endometrial cancer important in predicting risk to ovarian cancer? Yes it is.

If one of your relatives has had ovarian cancer, this can raise your chance over the baseline risk:

• the average woman has a 1% (1 in 70) lifetime risk of ovarian cancer
• having one first degree relative with ovarian cancer (mother, sister or daughter) gives a 5% lifetime risk for ovarian cancer
• having two first degree relatives increases the lifetime risk to 20-30%.

Randall TC, Rubin SC: Assessing a patient's risk for hereditary ovarian cancer. OBG Management 1998;Oct:37- 46, have examined the different risk factors for using a woman's family history of any cancer to determine if she is at risk for ovarian cancer. They report the general classification of hereditary ovarian cancer syndromes.

• breast-ovarian cancer syndrome
• Lynch syndrome in which family members may develop non polyposis-related colon or rectal carcinoma, endometrial carcinoma and in some cases, ovarian carcinoma
• site-specific ovarian cancer

In the breast-ovarian cancer syndrome, about 90% of cases can be explained by mutation in two genes, BRCA1 and BRCA2. These are the two breast/ovarian cancer genes that have been identified to date. Women who have these inherited genetic mutatations have as high as a 40-45% risk of ovarian cancer and as high as an 85% risk for breast cancer. If their relatives with breast or ovarian cancer have their disease onset at less than 50 years of age, or if they are of Ashkenazi Jewish heritage, that is even more suspicion that the family members carried the gene mutation.

In order to differentiate women who have a risk of an hereditary ovarian cancer syndrome (only about 5-10% of all ovarian cancers) versus just having relatives with cancer but no increased genetic risk, the following questions should be asked.

Well now that we've asked the questions and determined there is an increased risk for ovarian cancer, what are the next steps? With any increased risk due to family history, these authors reccomend:

• establish a complete family history with medical records if possible
• try to get genetic testing done on the family member with the cancer history if they are still alive
• armed with all the information possible, obtain good genetic counseling
• screen for early lesions using ultrasound and CA-125 starting at least 5 years before the earliest age of cancer onset in the family member
• consider chemoprevention such as oral contraceptives which can reduce the risk of hereditary cancer by 50% or more
• consider prophylactic removal of ovarian tissue only if the risk is proved to be substantial

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Hereditary Ovarian Cancer Reduced by Oral Contraceptives

Frederick R. Jelovsek MD

We've known since the early 1990's that use of birth control pills reduces a woman's risk for ovarian cancer by about 50%. The exact mechanism isn't known but it has been postulated that by keeping the ovary from ovulation each month, this reduces the exposure of the ovary to any cancer causing viruses or toxins. At ovulation, the inside of the ovary is opened in order to release an egg.

About 5 to possibly 10% of ovarian cancer, however, is associated with a genetic predisposition; it occurs in women with mutations in the BRCA1 or BRCA2 gene. If a woman has a BRCA1 mutation, her lifetime incidence of ovarian cancer is about 45% instead of the usual 1.4% in the general population. If there is a BRCA2 gene mutation, there is approximately a 25% lifetime incidence of ovarian cancer. For women who are known to have these gene mutations, the only suggested risk reduction therapies have been prophylactic oophorectomy and ultrasound screening, neither of which have been used enough to know the extent of the risk reduction.

In a recent article, Narod SA et al.: Oral contraceptives and the risk of ovarian cancer. N Engl J Med 1998; 339:424-8, the authors looked at whether or not oral contraceptives reduced the incidence of ovarian cancer in women who had a genetic risk by having either the BRCA1 or BRCA2 gene. They found that women who used oral contraceptives in the past were at lower risk for ovarian cancer even if they were positive for either BRCA gene. The magnitude of reduction was the same as it was for women overall, i.e., if women had used the pills 3 or less years, their risk was 80% of the risk for non-pill users. If a woman had used the pills for 3-6 years, her risk was 40%. Basically the risk dropped by 10% for each year the pill had been used although there did not seem to be a further reduction after 6 years of use.

There were some limitations of this study so we will hope that others also research this subject. For now, the data suggests that oral contraceptives should be part of a program of prevention for women with known BRCA1 or BRCA2 mutations.


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Fecal Occult Blood Testing - Detects Colorectal Cancer Earlier

Frederick R. Jelovsek MD

Screening for colon or rectal cancer has always been inexpensive but it is somewhat controversial as to whether it picks up cancer early enough to change the chance of dying from the disease. The test is performed by taking a stool sample, either as collected by the patient or as collected off of the glove after a rectal exam is performed. A chemical is then added which causes a color change if blood is present in the specimen. The problem is that tests can be positive even though there is no cancer present. Hemmorhoids can turn the test postive and even having eaten a rare steak the day before testing can produce a false positve test.

In order to identify factors associated with a diagnosis of early colorectal cancer, RE Myers and coworkers, Myers RE, Murray J, Weinberg D, McGrory G, Wolf T, Caveny J, Hanchak N, Schlackman N, Comis R. Analysis of colorectal cancer stage among HMO members targeted for screening. Arch Intern Med 1997;157(17):2001-2006, studied 222 men and women who were aged 50 years or older and had a diagnosis of colorectal cancer between 1987 and 1990 in a large HMO. Before diagnosis, all subjects were eligible for free annual fecal occult blood testing mailed to their home. They found that people who had testing were diagnosed at an earlier stage in their cancer. Patient age, gender, socioeconomic status, and frequency of screening history were not associated with earlier disease. These findings support annual fecal occult blood screening among older adults.

It is consistent with another study, Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O, Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348(9040):1467-1471. In which it was found that screening every two years resulted in less deaths from colorectal cancer.

See also at our Woman's Diagnostic Cyber Store:

Colocare® - the home fecal occult blood screening test

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Plant Estrogens and Breast Cancer

Frederick R. Jelovsek MD

Plant estrogen-like substances (phytoestrogens) are present in many grains, cereals and especially soy products. Women who have a high intake of soy products are known to have less menopausal hot flushes because of the estrogenic activity of these substances. Most of these phytoestrogens are very weak and it takes a moderate amount of dietary intake to notice an estrogen effect. A major question that occurs is whether the phytoestrogens have an estrogenic effect on breast cells.

In a recent study, Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control study of phyto-oestrogens and breast cancer. Lancet 1997;350(9083):990-994, looked at 144 women who had recently diagnosed breast cancer and compared them with an equal number of women matched for age and area of residence. They measured the amount of phytoestrogens excreted in the urine in all women. They found that the non-cancer women had higher levels of phytoestrogens in their urine than the women with cancer. This implies that diets high in plant estrogens may be protective against the development of breast cancer. In the 25% of non- cancer women who had the highest levels of excretion of plant estrogens, their risk for breast cancer was only about 25%.

It is always hazardous to postulate cause and effect from epidemiologic studies. While Ingram et al. concluded that phytoestrogens may protect against breast cancer, it may be merely that diets rich in plant estrogens replace other dietary substances that promote cancer. In fact, Welshons in Welshons WV, Murphy CS, Koch R, Calaf G, Jordan VC. Stimulation of breast cancer cells in vitro by the environmental estrogen enterolactone and the phytoestrogen equol. Breast Cancer Res Treat 1987;10(2):169-175, demonstrated that the same two phytoestrogens, equol and enterolactone, that "seemed to be protective" in the Ingram study, stimulated the growth of estrogen-dependent breast cancer cell lines. They suggested that these environmental agents can promote the growth of breast cancer, particularly hormone-dependent metastases that may be located near the gut or in the mesenteries or liver, where the concentration of these intestinally produced compounds would be highest.

How do we resolve these conflicts? The truth is that we don't, at least with respect to cause and effect. It is likely that something dietary IS associated with breast cancer. By increasing vegetable products at the expense of animal fats, women may be able to decrease their susceptability to cancer. But would this apply to taking soy or alfalfa concentrate supplements from the local health food store? We really don't know at this time.

Vulvar Cancer and Human Papilloma Virus (HPV)

By Frederick R. Jelovsek, M.D.

As with other genital cancers, vulvar cancer has a preinvasive phase in which changes can be detected in the skin of the vulva that precede an invasive malignancy. This preinvasive phase is called vulvar intraepithelial neoplasia (VIN). Human papilloma virus (HPV) has been suspected in playing a role in causing this rare cancer and some studies show that the DNA of a specific subtype of the virus (HPV-16) can be recovered in up to 80% of vulvar cancers. In one study by A. Hildesheim and others, Human Papillomavirus Type 16 and Risk of Preinvasive and Invasive Vulvar Cancer: Results From a Seroepidemiological Case- Control Study. Obstet Gynecol 1997; 90:748-54, the presence of blood HPV-16 antibodies were measured in patients who had recently diagnosed severe preinvasive vulvar dysplasia (VIN-3) and invasive cancer. They were compared to other paitents from the same geographical area that didn't have vulvar disease.

The authors found that more patients with vulvar disease had antibodies to HPV-16, i,e, they had been exposed to the virus at some time in the past. The risk ratio for preinvasive vulvar disease was over 20 times if a woman had HPV-16 antibodies. This was higher than even the risk for invasive cancer. Smoking and another virus antibody, herpes simplex virus type 2, were also independent risk factors. While the study didn't find as high a risk ratio for invasive vulvar cancer in general, it did find a higher risk for a type of vulvar cancer, a squamous carcinoma of a basaloid or warty type, more so than for a type called keratinizing squamous cell carcinoma.

What do these findings mean? They don't necessarily mean that HPV-16, HSV-type 2 and smoking cause vulvar cancer. They are somehow associated at with preinvasive vulvar cancer and possibly with one subtype of vulvar cancer. Smoking may suppress the local immune system and permit these viruses to induce skin cellular changes that can go on to cancer after many years. No one is absolutely sure. It does make another case against smoking, however. Also, venereal warts - condyloma accuminata - are thought to be caused by HPV virus and a woman that has a history of those warts should probably consider herself at higher risk for vulvar cancer as should a woman who has had a history of vulvar herpes lesions. A woman with a history of these problems doesn't need to panic, however, because these are still quite rare lesions that occur in the age decade of the 70's. Many more woman have these infections when younger and only a very small number ever develop a cancer.

If a woman has a history of such infections and especially if there is a recent smoking history, it would be wise to do regular self-exams of the vulva and to continue an annual physician visit after the age of 60 which includes the vulvar exam. Most vulvar cancers that physicians newly diagnose are women in their 70's and 80's who had quit going to their doctor for regular pelvic exams for many years.

PAP Smear Recommendations

By Frederick R. Jelovsek, M.D.,
Quillen College of Medicine -- Department of Obstetrics and Gynecology
East Tennessee State University

How often is a PAP smear necessary? Different doctors and organizations have different answers. A 1996 conference as recently reported in: Braly, P.S., The NIH consensus conference on cervical cancer: Implications for practice. Primary Care Update for Ob/Gyns 1997 (4):179-183, gave some consensus guidelines.

PAP smears should be started when sexual activity starts or at age 18, whichever is earlier. Three annual PAP smears should performed and after that, smears can be less than annually if a patient is low risk. Few women qualify as low risk, meaning no more than two lifetime sexual partners and a partner with no more than two lifetime partners. Thus many women should continue to have a yearly PAP smear and after age 65, all women should have an annual exam.

Other risk factors for cervical cancer include smoking, lower socioeconomic status, age, having had multiple pregnancies, immunosuppression, and sexually transmitted diseases - especially human papilloma virus (HPV) which is found in 100% of cervical cancers. Certain strains of HPV, types HPV-16, -18, -31, and -45, are high risk and account for 80% of cervical cancer. In spite of this knowledge, there is still no consensus about screening patients who have abnormal PAP smears for these HPV virus types. Studies are ongoing to see if this additional screening in addition to the PAP smear is cost-justified. Most investigators believe that it not only takes years for the progression from HPV infection to malignancy but that it is apparent that the infection alone is not sufficient for the development of cervical cancer. Other cofactors are needed in addition to HPV. Tobacco carcinogenic and mutagenic substances, compromised immune status, dietary deficiencies, radiation exposure and coexisting viral and bacterial infections are thought to somehow enhance a malignant transformation.

It is estimated that as many as 5-20% of persons 15-49 years old are infected with HPV. Vaccines against HPV are currently being developed but they are not going to be available in the near future. If you have ever had abnormal PAP smears or had venereal warts (HPV infection, condyloma accuminata), you should be sure to get an annual PAP smear for the rest of your life.
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