ACOG spells out risk assessment for hereditary cancer syndromes



To identify patients at increased risk for certain types of cancer, ob.gyns. should perform and regularly update hereditary cancer risk assessments, according to a new recommendation from the American College of Obstetricians and Gynecologists.

Patients at increased risk for hereditary cancer syndromes should be referred to a cancer genetics specialist for further assessment and counseling, according to the opinion from ACOG’s Committee on Genetics (Obstet. Gynecol. 2015;125:1538-43).

Alexander Raths/

Personal and family histories provide key information to determine the appropriateness of genetic counseling, which is distinct from genetic testing. Discussed in the counseling visit, the decision for genetic testing is based on family history, pedigree analysis, and, in some cases, pathology reports and confirmation of cancer deaths.

Patient intake forms are used in many office settings to gather relevant information. Online versions of intake forms, such as the Surgeon General’s “My Family Health Portrait,” can facilitate documentation of comprehensive histories. The American Society of Clinical Oncology also has identified some key elements of an adequate family history for assessing cancer risk, including first- and second-degree relatives, maternal and paternal sides, European Jewish ancestry, age of onset and type of cancer, and results of predisposition tests in any relative.

There are several indicators for the presence of hereditary cancer syndromes, including cancer diagnosed at an unusually young age, the presence of several different types of cancer, several close relatives with the same type of cancer, unusual presentation (such as breast cancer in a man), certain birth defects (such as skin growths or skeletal abnormalities associated with inherited cancer syndromes), and Ashkenazi Jewish ancestry.

The ACOG committee opinion identifies common hereditary cancer syndromes involved in gynecologic cancers, including hereditary breast and ovarian cancer syndrome and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes.

Mutations in DNA repair genes BRCA1 and BRCA2 cause hereditary breast and ovarian cancer syndrome and account for 5%-15% of all breast and ovarian cancers in the United States. The carrier frequency in the general population is 1 in 500, but it is much higher (1 in 40) in the Ashkenazi Jewish population. Women with hereditary breast and ovarian cancer syndrome have a 65%-74% lifetime risk of breast cancer and 39%-46% (BRCA1) or 12%-20% (BRCA2) risk of ovarian cancer.

Also caused by DNA repair defects, Lynch syndrome, or hereditary nonpolyposis colorectal cancer, has a prevalence of 1 in 600 to 1 in 3,000. Individuals with Lynch syndrome have increased risk of colon (52%-82%), endometrial (25%-60%), and ovarian (4%-24%) cancers. Malignancies associated with Lynch syndrome include uterine, gastric, small bowel, hepatobiliary, breast, brain, and sebaceous skin cancers.

The presence of Li-Fraumeni syndrome increases the risk of osteosarcoma, breast cancer, colon cancer, adrenocortical carcinoma, leukemia and lymphoma, and brain cancer. Caused by mutations in the tumor suppressor gene TP53, individuals with the syndrome have a 90% risk of cancer by age 60 years. Patients diagnosed with a Li-Fraumeni syndrome–associated malignancy should be referred to a cancer genetics specialist for counseling, according to the committee opinion.

Individuals with the relatively rare (1 in 200,000) Cowden syndrome usually have pathognomonic skin lesions, including papillomatous papules on the face and mucous membranes, by age 30 years. The presence of Cowden syndrome increases the lifetime risk of breast cancer to 25%-50% and endometrial cancer to 5%-10%. Clinicians should consult frequently updated guidelines to determine which patients should be referred for genetic evaluation.

Mutations in serine/threonine kinase 11 cause Peutz-Jehgers syndrome. Two of the following three criteria characterize the syndrome: two or more hamartomatous polyps in the GI tract; mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitalia, or fingers; and a family history of Peutz-Jeghers syndrome. Women with Peutz-Jeghers syndrome have a 50% increased lifetime risk of breast cancer and increased risk of ovarian, uterine, and cervical cancer.

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