Point-of-Care Guides

Estimating the Risk of Ovarian Cancer



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Am Fam Physician. 2009 Sep 15;80(6):632-634.

  Related Article

Clinical Question

What is a patient's risk of ovarian cancer?

Evidence Summary

Every year, 25,000 women in the United States (about one in 3,000 women older than 40 years) receive ovarian cancer diagnoses, and 14,000 die of the disease.1 Risk factors for ovarian cancer include family history of ovarian cancer, personal history of breast cancer, obesity, not breastfeeding, infertility, or giving birth to no or few children. Tubal ligation, oral contraceptive use, and hysterectomy are associated with lower risk.2,3

In women who have a first-degree relative with ovarian cancer, the relative risk is 3.1 (95% confidence interval [CI], 2.6 to 3.7).2 Given that the overall risk of developing ovarian cancer by 65 years of age is 0.8 percent and the lifetime risk is 1.8 percent, the relative risk increases to 4.4 and 9.4 percent, respectively, among women with an affected first-degree relative.4

The Nurses' Health Study found that ever using an oral contraceptive for five or more years, having been pregnant at least twice, having breastfed for at least one year, and having had a hysterectomy or tubal ligation modestly reduced the risk of ovarian cancer (relative risk = 0.6 to 0.8).4 A study that evaluated the impact of number of pregnancies and duration of oral contraceptive use found that these factors had a relatively small impact on the absolute risk of ovarian cancer, with a lifetime risk ranging from 0.6 percent in the lowest risk group to 3.6 percent in the highest risk group.4

The BRCA1 or BRCA2 gene mutation increases the lifetime risk of ovarian cancer to between 10 percent (BRCA2) and 26 percent (BRCA1).5  About 2 percent of women are candidates for screening and genetic counseling according to U.S. Preventive Services Task Force (USPSTF) guidelines (Table 1).6 The USPSTF does not recommend routine screening for ovarian cancer using cancer antigen (CA) 125 testing, ultrasonography, or other tests.7

Table 1

Women Who Should Be Offered Testing and Genetic Counseling for BRCA1 and BRCA2 Mutations

Ashkenazi Jewish women with:

One first-degree relative with breast or ovarian cancer

Two second-degree relatives on the same side of the family with breast or ovarian cancer

All other women with:

Two first-degree relatives with breast cancer, one of whom was diagnosed by 50 years of age

Three or more first- or second-degree relatives with breast cancer

A combination of breast and ovarian cancers among first- and second-degree relatives

One first-degree relative with bilateral breast cancer

Two or more first- or second-degree relatives with ovarian cancer

One first- or second-degree relative with both breast and ovarian cancers

Breast cancer in a male relative


Information from reference 6.

Table 1   Women Who Should Be Offered Testing and Genetic Counseling for BRCA1 and BRCA2 Mutations

View Table

Table 1

Women Who Should Be Offered Testing and Genetic Counseling for BRCA1 and BRCA2 Mutations

Ashkenazi Jewish women with:

One first-degree relative with breast or ovarian cancer

Two second-degree relatives on the same side of the family with breast or ovarian cancer

All other women with:

Two first-degree relatives with breast cancer, one of whom was diagnosed by 50 years of age

Three or more first- or second-degree relatives with breast cancer

A combination of breast and ovarian cancers among first- and second-degree relatives

One first-degree relative with bilateral breast cancer

Two or more first- or second-degree relatives with ovarian cancer

One first- or second-degree relative with both breast and ovarian cancers

Breast cancer in a male relative


Information from reference 6.

Ovarian cancer may cause a variety of symptoms, and several well-designed studies have identified the most important independent predictors of the disease in symptomatic women. In a case-control study of 1,709 women visiting their primary care physicians (44 of the women had ovarian cancer), signs and symptoms of cancer included increased abdominal size (odds ratio [OR] = 7.4); abdominal mass (OR = 5.4); bloating (OR = 3.6); urinary urgency (OR = 2.5); pelvic pain (OR = 2.2); and a combination of bloating, increased abdominal size, and urinary urgency (OR = 9.4).8 However, given the low pretest probability of ovarian cancer, the likelihood of cancer in women with one or more of these symptoms is quite low. The study also found that cancer was more common in women with shorter symptom duration (e.g., malignancy is unlikely in a woman reporting bloating for five years), or with more frequent or severe symptoms.8

A second case-control study found that any of six symptoms (pelvic or abdominal pain, increased abdominal size, bloating, difficulty eating, feeling full) occurring more than 12 times a month for less than one year made up a useful symptom index.9  Table 2 presents the accuracy of this symptom index alone and in combination with CA 125 level (a biomarker used to monitor for recurrence of ovarian cancer).10 Although the positive predictive value is somewhat higher in women with a family history of ovarian cancer, it is important to note that only about 5 percent of women diagnosed with ovarian cancer have such a history; most cases are sporadic.4

Table 2

Accuracy of a Symptom Index With or Without CA 125 Testing for the Diagnosis of Ovarian Cancer

Symptom index/CA 125 findings* Sensitivity (%) Specificity (%) LR+ LR– Positive predictive value
Women with average risk(%) Women with family history of ovarian cancer(%)

Positive symptom index alone

64.0

88.2

5.4

0.41

0.18

0.5

Abnormal CA 125 level alone

78.7

95.3

16.7

0.22

0.56

1.6

Positive symptom index or abnormal CA 125 level

89.3

83.5

5.4

0.13

0.18

0.5

Positive symptom index and abnormal CA 125 level

53.3

100

107

0.47

3.4

9.6


CA = cancer antigen; LR– = negative likelihood ratio; LR+ = positive likelihood ratio.

*— [corrected] A positive symptom index is pelvic or abdominal pain, increased abdominal size, bloating, difficulty eating, or feeling full more than 12 times a month for less than one year. An abnormal CA 125 level is greater than 30 units per mL (30 arb units per L).

†— Average risk is based on an annual incidence of one in 3,000 average women, which corresponds to a pretest probability of 0.033 percent.

‡— Women with a first-degree relative with ovarian cancer have a threefold higher risk of one in 1,000 (approximately 0.1 percent).

Information from reference 10.

Table 2   Accuracy of a Symptom Index With or Without CA 125 Testing for the Diagnosis of Ovarian Cancer

View Table

Table 2

Accuracy of a Symptom Index With or Without CA 125 Testing for the Diagnosis of Ovarian Cancer

Symptom index/CA 125 findings* Sensitivity (%) Specificity (%) LR+ LR– Positive predictive value
Women with average risk(%) Women with family history of ovarian cancer(%)

Positive symptom index alone

64.0

88.2

5.4

0.41

0.18

0.5

Abnormal CA 125 level alone

78.7

95.3

16.7

0.22

0.56

1.6

Positive symptom index or abnormal CA 125 level

89.3

83.5

5.4

0.13

0.18

0.5

Positive symptom index and abnormal CA 125 level

53.3

100

107

0.47

3.4

9.6


CA = cancer antigen; LR– = negative likelihood ratio; LR+ = positive likelihood ratio.

*— [corrected] A positive symptom index is pelvic or abdominal pain, increased abdominal size, bloating, difficulty eating, or feeling full more than 12 times a month for less than one year. An abnormal CA 125 level is greater than 30 units per mL (30 arb units per L).

†— Average risk is based on an annual incidence of one in 3,000 average women, which corresponds to a pretest probability of 0.033 percent.

‡— Women with a first-degree relative with ovarian cancer have a threefold higher risk of one in 1,000 (approximately 0.1 percent).

Information from reference 10.

Diagnosing ovarian cancer is an important clinical challenge. The data described above suggest that physicians should consider ovarian cancer in women presenting with new, frequent gastrointestinal or urinary tract symptoms (or both) of relatively short duration, especially if there is a family history of the disease. Generally, transvaginal ultrasonography is recommended as the best initial test to rule out ovarian cancer. One study found that transvaginal ultrasonography was 95 percent sensitive and 91 percent specific at distinguishing benign from malignant ovarian masses (positive likelihood ratio = 10.4, negative likelihood ratio = 0.06).11

Applying the Evidence

A 62-year-old woman reports being bloated and feeling full on most days of the previous four months. She has tried modifying her diet with only minimal benefit. Three years ago, her sister received an ovarian cancer diagnosis, and the patient is concerned that she may have the disease as well. What is the likelihood that the patient has ovarian cancer?

Answer: Using the symptom index in Table 2,10 you determine that she has a 0.5 percent (one in 200) chance of having ovarian cancer. Because the patient is concerned about the discomfort of transvaginal ultrasonography, you obtain a CA 125 measurement to better stratify her risk. Her CA 125 level is abnormal; and, given her nearly 10 percent risk of ovarian cancer, she agrees to proceed with the ultrasound study.

MARK H. EBELL, MD, MS, is an associate professor in the Dept. of Epidemiology and Biostatistics in the College of Public Health at the University of Georgia, Athens.

Address correspondence to ebell@uga.edu. Reprints are not available from the author.

Author disclosure: Nothing to disclose.

REFERENCES

1. Myers ER, Bastian LA, Havrilesky LJ, et al. Management of adnexal mass. Evid Rep Technol Assess (Full Rep). 2006;(130):1–145.

2. Stratton JF, Pharoah P, Smith SK, Easton D, Ponder BA. A systematic review and meta-analysis of family history and risk of ovarian cancer. Br J Obstet Gynaecol. 1998;105(5):493–499.

3. Kim DJ, Rockhill B, Colditz GA. Validation of the Harvard Cancer Risk Index: a prediction tool for individual cancer risk. J Clin Epidemiol. 2004;57(4):332–340.

4. Hartge P, Whittemore AS, Itnyre J, McGowan L, Cramer D. Rates and risks of ovarian cancer in subgroups of white women in the United States. The Collaborative Ovarian Cancer Group. Obstet Gynecol. 1994;84(5):760–764.

5. Nelson HD, Huffman LH, Fu R, Harris EL. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence review for the U.S. Preventive Services Task Force [published correction appears in Ann Intern Med. 2005;143(7):547]. Ann Intern Med. 2005;143(5):362–379.

6. U.S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendation statement [published correction appears in Ann Intern Med. 2005;143(5):355–361]. Ann Intern Med. 2005;143(5):355–361.

7. Agency for Healthcare Research and Quality. U.S. Preventive Services Task Force. Screening for Ovarian Cancer. http://www.ahrq.gov/clinic/uspstf/uspsovar.htm. Accessed February 12, 2009.

8. Goff BA, Mandel LS, Melancon CH, Muntz HG. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 2004;291(22):2705–2712.

9. Goff BA, Mandel LS, Drescher CW, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007;109(2):221–227.

10. Andersen MR, Goff BA, Lowe KA, et al. Combining a symptoms index with CA 125 to improve detection of ovarian cancer. Cancer. 2008;113(3):484–489.

11. Timmerman D, Testa AC, Bourne T, et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008;31(6):681–690.

This guide is one in a series that offers evidence-based tools to assist family physicians in improving their decision making at the point of care.


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