Overview

Information about the prevention of cancer and the science of screening appropriate individuals at high risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.

Ovarian cancer has the highest mortality rate of all gynecologic cancers. It is the fifth leading cause of cancer death among U.S. women, with a projected 21,650 new cases and 15,520 deaths in the year 2008.[1]

The causes of ovarian cancer are poorly understood. However, researchers have evaluated risk factors associated with ovarian cancer. A few risk factors have been identified and others are suspected.

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.

Heredity and Genetic Factors

An estimated 5-10% of ovarian cancers are due to inherited gene mutations. Women with mutations in the BRCA1 or BRCA2 genes, for example, have a high risk of both breast and ovarian cancer. Estimates of the lifetime risk of ovarian cancer among women with a BRCA1 or BRCA2 gene mutation range from 10% to 68%.[2] Preventive surgery to remove the ovaries before cancer develops is one approach to reduce the risk of ovarian cancer among women at high risk of the disease.

In addition, even among women without a BRCA1 or BRCA2 mutation, those with a family history of ovarian cancer (particularly in a close relative such as a mother, sister, or daughter) are at increased risk of developing the disease.

Environmental or Non-Genetic Factors

Factors linked with a reduced risk of ovarian cancer include use of oral contraceptives; tubal sterilization (tubal ligation); and an increasing number of full-term pregnancies.[3] Breastfeeding has also been linked with a reduced risk of ovarian cancer.[4]

A factor that may increase the risk of ovarian cancer is use of postmenopausal hormones.[5] [6]

As researchers continue to explore environmental and behavioral risk factors for ovarian cancer, it’s increasingly becoming clear that some factors are linked only with specific types of ovarian cancer (serous, endometrioid, mucinous, etc). For example, smoking has been reported to increase the risk of mucinous ovarian cancer but not other types of ovarian cancer.[7] Additional research along these lines may provide important clues to the causes of ovarian cancer, and may also suggest additional approaches to prevention.

Prevention

Research into the risk factors for ovarian cancer has provided important clues about steps women can take to reduce their risk of the disease.

Removal of the Ovaries: In women who have a strong family history of ovarian cancer or the presence of a BRCA1 or BRCA2 mutation, removal of the ovaries before cancer develops (prophylactic oophorectomy) can greatly reduce ovarian cancer risk.[8] Surgery doesn’t completely eliminate ovarian cancer risk because some cells remain behind after surgery. Removal of the ovaries also reduces the risk of breast cancer since some breast cancers don’t grow well without the hormones produced by the ovaries. Women with a BRCA1 or BRCA2 alteration who have had their ovaries removed have about half the risk of developing breast cancer as those who have not had their ovaries removed.8

Following removal of the ovaries, women will likely experience menopausal symptoms such as hot flashes. These symptoms are often more severe in women who have their ovaries removed surgically than in women who reach menopause naturally. Removal of the ovaries also means that a woman will be unable to have children. Some women may therefore choose to postpone surgery until after they’ve completed their families. Ovarian cancer in BRCA1 and BRCA2 carriers most often occurs after age 40.[9]

Oral Contraceptives: Oral contraceptives reduce the risk of ovarian cancer, and longer-term use provides a greater reduction in ovarian cancer risk than shorter-term use.[10] Because oral contraceptives can have a range of health effects, however, decisions about the use of oral contraceptives should be made on an individual basis, in consultation with a health care professional.

Diet: Although there is a great deal of interest in the relationship between diet and cancer, it remains uncertain whether and how diet affects the risk of ovarian cancer. Nevertheless, women are advised to follow general recommendations for a healthy diet: eat a diet that’s rich in whole grains, fruits, and vegetables; limit intake of red or processed meat; limit alcohol intake to one drink per day; and choose foods that help you maintain a healthy weight.[11]

Exercise: As is the case for diet, the relationship between exercise and ovarian cancer remains uncertain. But regardless of whether it reduces the risk of ovarian cancer, exercise provides many other important health benefits, such as a reduced risk of heart disease and colon cancer. Your doctor can help you find an exercise program that’s right for you. Current recommendations suggest at least 30 minutes of moderate to vigorous physical activity on five or more days per week. [12]

Screening and Early Detection of Ovarian Cancer

For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the routine use of certain examinations or tests in persons who do not have any symptoms of a cancer in order to try to diagnose a developing cancer at the earliest possible stage. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.

The predictive value of screening may be greater for women who are at a high risk of developing ovarian cancer, but whether screening will allow for early detection and improve survival among such women remains unknown.

Annual Pelvic Examination: Currently, the most widely utilized way to detect ovarian cancer is to undergo a complete gynecologic examination at least once per year. Because ovarian cancers begin deep in the pelvis, they often do not cause any symptoms until they are at an advanced stage. In order to improve outcomes for women with ovarian cancer, the disease has to be diagnosed early, before it spreads.

Pay Attention to Symptoms: According to a consensus statement developed by the American Cancer Society, the Gynecologic Cancer Foundation, and the Society of Gynecologic Oncologists, certain symptoms are more likely to occur in women with ovarian cancer than women in the general population:

  • Bloating
  • Pelvic or abdominal pain
  • Difficulty eating or feeling full quickly
  • Urinary symptoms (urgency or frequency)

Women who experience these symptoms almost daily for more than a few weeks are encouraged to see a doctor, preferably a gynecologist. [13]

Transvaginal ultrasound plus CA-125 testing: For women who have a BRCA1 or BRCA2 mutation, ovarian cancer screening using a combination of transvaginal ultrasound and serum CA-125 testing may be recommended, even in the absence of firm evidence that it reduces ovarian cancer mortality.[14] Women with a BRCA1 or BRCA2 mutation are advised to talk with their physician about the optimal approach to risk reduction or surveillance.

Strategies to Improve Screening and Early Detection

Potential approaches to screening for ovarian cancer include transvaginal ultrasound and measurement of serum CA-125 levels, but thus far there is no firm evidence that these tests reduce ovarian cancer mortality. To improve upon currently available tests, researchers are exploring new approaches to early detection, such as combining several different blood tests,[15] or using a combination of blood test and symptom results.[16]

References:

[1] American Cancer Society. Cancer Facts & Figures 2008. Available at: http://www.cancer.org/docroot/STT/stt_0.asp (Accessed September 29, 2008).

[2] National Cancer Institute. Genetics of Breast and Ovarian Cancer (PDQ®). Available at: http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page1  (Accessed November 17, 2008.

[3] Bertone-Johnson ER. Epidemiology of ovarian cancer: a status report. Lancet. 2005;365:101-102.

[4] Danforth KN, Tworoger SS, Hecht JL, Rosner BA, Colditz GA, Hankinson SE. Breastfeeding and risk of ovarian cancer in two prospective cohorts. Cancer Causes and Control. 2007;18:517-23.

[5] Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in the Million Women Study. The Lancet. 2007;369:1703-10.

[6] Lacey JV, Brinton LA, Leitzmann MF et al. Menopausal Hormone Therapy and Ovarian Cancer Risk in the National Institutes of Health-AARP Diet and Health Study Cohort. Journal of the National Cancer Institute. 2006;98:1397-405.

[7] Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM. Does smoking increase the risk of ovarian cancer? A systematic review. Gynecologic Oncology. 2006;103:1122-9.

[8] Rebbeck TR, Lynch HT, Neuhausen SL et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616-1622.

[9] Hogg R, Friedlander M. Biology of epithelial ovarian cancer: implications for screening women at high genetic risk. J Clin Oncol. 2004; 22:1315-1327.

[10] Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303-314.

[11] Kushi LH, Byers T, Doyle C et al. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity. CA Cancer J Clin 2006 56: 254-281

[12] Kushi LH, Byers T, Doyle C et al. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity. CA Cancer J Clin 2006 56: 254-281

[13] American Cancer Society. Ovarian cancer has early symptoms. First national consensus on common warning signs. Available at: http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Ovarian_Cancer_Symptoms_The_Silence_Is_Broken.asp (Accessed November 18, 2008).

[14] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology.™ Genetic/Familial High-Risk Assessment: Breast and Ovarian. V.1.2008. © National Comprehensive Cancer Network, Inc. 2008. NCCN® and NATIONAL COMPREHENSIVE CANCER NETWORK® are registered trademarks of National Comprehensive Cancer Network, Inc.

[15] Visintin I, Feng Z, Longton G, et al. Diagnostic markers for early detection of ovarian cancer. Clinical Cancer Research [early online publication] February 7, 2008. DOI: 10.1158/1078-0432.

[16] Andersen M, Goff B, Lowe K, et al. Combining a symptoms index with CA 125 to improve detection of ovarian cancer. Cancer [early online publication]. June 2008. DOI: 10.1002/cncr.23577.