Ovulation is considered a hostile event to the ovarian epithelium, making it more susceptible to damage and cancer. Interventions or conditions that limit the number of ovulations in a woman's reproductive history, including multiparity, will have a protective effect.

Chemoprevention Investigational chemoprevention strategies used for ovarian cancer include oral contraceptives (OCs), aspirin and nonsteroidal anti-inflammatory agents, and retinoids, although none of these is currently accepted as standard treatment for the prevention of ovarian cancer. The theory that OCs reduce the number of ovulatory events is a basic explanation of its protective effect. Recent studies have suggested that progestin-induced apoptosis of the ovarian epithelium is responsible for the chemopreventive effect of OCs. The theory is that cells that have genetic damage, but are not yet neoplastic, have an increased chance of undergoing apoptosis.10 OCs decrease the relative risk to less than 0.4% in women that use OCs for greater than 10 years.11 However, the maximum protective effect of OC use in women with

BRCA mutations has been reported to be between 3 and 5 years. However, at the


same time, OC use has been associated with an increased risk of breast cancer. Thus, women with a family history of breast cancer would not be ideal candidates for this preventative measure.

Nonsteroidal anti-inflammatory agents, aspirin, and acetaminophen have been suggested for use in the prevention of different cancers, especially hereditary nonpoly-posis colon cancer.13 While there have been observational studies linked to a reduction of ovarian carcinoma risk, evidence is still lacking. Potential mechanisms include effects on normal ovulation shed and inhibition of ovulation.13,14 Other pharmacologic interventions that have been suggested but are still being evaluated include vitamin A, lutein, and other carotenoids. -17 The protective effect of these agents is associated with inhibition of cell growth as well as promotion of cellular differentiation.16

Prophylactic Surgery Surgical strategies are also used in the prevention of ovarian cancer. The goal is to remove healthy, at-risk organs and ultimately reduce the risk of developing cancer. These surgeries include prophylactic bilateral salpingo-oo-phorectomy (BSO) or tubal ligation.

Prophylactic oophorectomy should be considered in any woman with a high risk of developing ovarian cancer.18 The criteria for defining high risk includes any woman with two or more first-degree relatives with epithelial ovarian carcinoma, a family history of multiple occurrences of nonpolyposis colon cancer, endometrial cancer, and ovarian cancer, and a family history of multiple cases of breast and ovarian cancer.18 Patients undergoing prophylactic oophorectomy need to be made aware that complete protection is not guaranteed.11,19 Although a 67% reduction in risk has been shown, a potential 2% to 5% risk of peritoneal carcinomatosis remains.18,20

Tubal ligation is another procedure that has shown potential for risk reduction. However, it is not recommended as a sole procedure in prophylaxis. Protective effect may be due to the limiting exposure of the ovary to environmental carcinogens. A case-control study conducted by Narod and colleagues found that a history of tubal ligation in BRCA-positive women was associated with a statistically significant 63% reduction in risk.2

Genetic Screening Genetic screening is another option available for high-risk patients. Patients can be screened for genes such as BRCA1, BRCA2, or other genes such

as those associated with HNPCC or the HBOC syndrome. ' Patient/family counseling and genetic counseling should be available for the patient/family to prepare and deal with the health and psychosocial implications of the genetic test results. Prior to this decision, the potential preventative options should be discussed, such as prophylactic BSO and/or total hysterectomy. Patients specifically positive for BRCA1 or

BRCA2 may also consider a mastectomy. Cancer risk and patient's health need to be balanced, but typically surgery can be held off until after the childbearing years.25-27

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