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Counseling Women at High Risk of Ovarian or Endometrial Cancer

Counseling Women at High Risk of Ovarian or Endometrial Cancer

ABSTRACT: Click here to link to the CME post-test for this article.

ABSTRACT: Certain women are at very high risk for developing ovarian and/or endometrial cancer. Although endometrial cancer tends to be diagnosed at an earlier stage and often can be managed successfully using a multimodality treatment regimen, ovarian cancer is typically diagnosed at an advanced stage, carrying a high mortality rate and causing more deaths than any other type of female reproductive cancer. About 10% of ovarian cancers are hereditary, with the majority attributable to BRCA1 and BRCA2 gene mutations. Whereas the average woman has a 1.7% lifetime risk of developing ovarian cancer, women with hereditary breast and ovarian cancer (HBOC) resulting from a BRCA1 or BRCA2 gene mutation have a lifetime ovarian cancer risk up to 44%. Potentially lifesaving cancer screening and prevention options can be offered to at-risk women who have undergone appropriate clinical testing and counseling. This article will describe the etiology of ovarian and endometrial cancer, personal histories and genetic factors that can place women at high-risk for these malignancies, screening modalities for ovarian and endometrial cancer, and preventive options.

The second most common gynecologic cancer among women, ovarian cancer causes more deaths than any other type of female reproductive cancer.[1] The average woman has a 1.7% lifetime risk of developing ovarian cancer, with the median age at onset being 63 years.[2] In contrast, women with hereditary breast and ovarian cancer resulting from a BRCA1 or BRCA2 gene mutation have a lifetime ovarian cancer risk up to 44%. The majority of ovarian cancers are sporadic, or nonhereditary. Only approximately 10% of ovarian cancer cases are hereditary.[3–5]

Ovarian cancer is difficult to detect early and is most commonly diagnosed at an advanced stage (stage III or IV). The overall 5-year survival rate of women with advanced ovarian cancer is only 20% to 30%. If ovarian cancer were detected in its early stages, however, the survival rate would improve significantly.[6] The difficulty is that the signs and symptoms of early-stage ovarian cancer are often vague, not specific to the disease, and may be attributed to other factors, such as a common bladder or digestive problem, often delaying the diagnosis. However, the symptoms of ovarian cancer tend to persist and worsen with time. As the cancer increases in size, symptoms may include pressure or pain in the abdomen, pelvis, back, or legs; a swollen or bloated abdomen; nausea, indigestion, gas, constipation, or diarrhea; and fatigue. Less common symptoms include shortness of breath, urinary urgency, and unusual vaginal bleeding (heavy periods or bleeding after menopause) (Table 1).[7] Ovarian cancer is frequently described as the “silent killer” because it often is diagnosed late in the disease trajectory, when the prognosis is poor.

Signs and Symptoms of Ovarian and Endometrial Cancer

Endometrial cancer is the most common gynecologic malignancy, and the fourth most common cancer in women.[1] Diagnoses in women younger than 50 years of age have been linked to a number of risk factors, including obesity and hereditary cancer syndromes such as Lynch syndrome. The average woman has a 2% to 3% lifetime risk of endometrial cancer, as compared with a 40% to 60% risk of this malignancy in women with Lynch syndrome.[8–10] Endometrial cancer is highly curable if it is detected early. An endometrial biopsy, not a Pap smear, is necessary for the diagnosis of uterine cancer. The signs and symptoms of endometrial cancer include abnormal uterine bleeding; abnormal menstrual periods; bleeding between normal periods before menopause; vaginal bleeding or spotting after menopause; extremely long, heavy, or frequent episodes of vaginal bleeding after age 40; and lower abdominal pain or cramping accompanied by a thick white or clear vaginal discharge after menopause (Table 1).[11,12]

It is important to educate patients, especially those with a substantially increased risk of ovarian and endometrial cancer, to be aware of any symptoms suggestive of these cancers. Symptoms of ovarian cancer tend to be more severe and seem different compared with how a woman “usually” feels. Women are strongly encouraged to call their physicians, preferably their gynecologists, if these symptoms occur almost daily for more than a few weeks and cannot be explained by other more common conditions.

Hereditary Ovarian Cancer Syndromes

The majority of hereditary breast and ovarian cancers are attributable to deleterious mutations in the BRCA1 and BRCA2 genes.[13–15] A recent meta-analysis estimated the lifetime risk of breast cancer to be 47% to 66% in BRCA1 mutation carriers and 40% to 57% in BRCA2 mutation carriers. The ovarian cancer risk was estimated to be 35% to 46% in BRCA1 mutation carriers and 13% to 23% in BRCA2 mutation carriers.[13–18] Women with a BRCA1/BRCA2 mutation are at risk not only of developing ovarian cancer, but also fallopian tube and primary peritoneal cancer.[19] BRCA1 and BRCA2 mutations also have been associated with male breast cancer, prostate cancer, and pancreatic cancer.[13–18] The average age of onset of ovarian cancer in women with a BRCA1 mutation is 50.8 years and in women with a BRCA2 mutation is 57.1 years.[16] Therefore, women with BRCA1 or BRCA2 mutations have a substantially higher risk of developing ovarian cancer at a younger age compared with the age at which sporadic ovarian cancer occurs among women in the general population.

When reviewing a patient’s personal and family history, there are several indicators of an increased risk of hereditary breast and ovarian cancer, including:

• multiple family members affected by early-onset breast cancer diagnosed before age 50 or ovarian cancer at any age;

• bilateral breast cancer;

• multiple primary cancers in an individual;

• male breast cancer; and

• Ashkenazi Jewish ancestry.[20]

NCCN Hereditary Breast and/or Ovarian Cancer Syndrome Testing Criteria

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC), is another hereditary cancer syndrome associated with an increased risk for ovarian cancer, as well as cancer of the endometrium, colon and rectum, stomach, small bowel, ureter, and renal pelvis, with these risks attributable to mutations in one of the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). Women with Lynch syndrome have a 7% to 12% lifetime risk of ovarian cancer, a 40% to 60% lifetime risk of endometrial cancer, and a 30% to 52% lifetime risk of colon cancer.[8–10] Other, more rare, hereditary cancer predisposition syndromes increasing a woman’s risk of gynecologic cancers include Li Fraumeni syndrome,[21] Peutz-Jeghers syndrome,[22] and Cowden syndrome.[23]

Identification of High-Risk Patients

At MD Anderson Cancer Center (MDACC), patients are identified as potentially at-risk for a hereditary cancer syndrome by their treating physician and referred to a genetic counselor within the institution for an evaluation. Guidelines and a variety of criteria can be used to establish whether a patient is eligible for BRCA1 and BRCA2 genetic testing (Table 2).

National testing guidelines are utilized during the genetic consultation, at which point the patient’s personal and family histories are reviewed, a risk assessment is performed, hereditary cancers are discussed, and genetic testing (if appropriate) is recommended. If a family member has been diagnosed with cancer and is alive, it is recommended that he or she proceed with genetic testing prior to testing of an unaffected family member, in order to provide the most accurate information for the family. Based on genetic test results and/or a strongly suggestive family history of cancer, a patient may have an inherited risk of ovarian or endometrial cancer—and thus a substantially increased likelihood of developing these malignancies. If this is the case, then the patient is referred to be evaluated and managed in the high-risk ovarian cancer screening clinic.

Eligibility Criteria for High-Risk Ovarian Screening

Eligibility criteria were established for the high-risk ovarian screening clinic at MDACC to limit patients seen in the clinic to women with a significantly increased risk of ovarian or endometrial cancer based on a deleterious mutation consistent with a hereditary predisposition cancer syndrome or a strongly suggestive family history (Table 3).

If a patient requests an appointment in the high-risk ovarian screening clinic but does not meet these eligibility criteria, she is first referred to a genetic counselor to confirm whether the patient is, in fact, at high risk of ovarian or endometrial cancer. A thorough family history is obtained and genetic testing may be recommended for the patient or family member(s) with a history of cancer. This enables the genetic counselor to more accurately determine the patient’s risk of cancer prior to referral to the high-risk ovarian cancer screening clinic and ensures that only patients who are truly at high risk are managed and followed.


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