Obstetrician-gynecologists play a unique role in screening women for various malignancies, including breast, colon, and cervical carcinoma. Although less common, genetic syndromes also can affect the female reproductive tract; therefore, knowledge of the screening guidelines for the most common genetic syndromes – hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome, and Cowden syndrome – is important.
Hereditary breast and ovarian cancer syndrome
Caused by autosomal-dominant deletions in the BRCA1/2 genes, the lifetime risk of ovarian cancer in patients with a BRCA1 and BRCA2 mutation is 39%-46% and 12%-20%, respectively. Although not proven to improve detection or survival, the American College of Obstetricians and Gynecologists (ACOG) and National Comprehensive Cancer Network (NCCN) guidelines recommend that women with BRCA1/2 mutations should undergo screening with transvaginal ultrasonography and CA125 every 6 months beginning between ages 30-35 years or 5-10 years prior to the age of the youngest affected family member. For patients who have not completed childbearing, a recent meta-analysis showed that use of oral contraceptives was associated with a decreased risk of ovarian cancer in patients with BRCA1/2 (J. Clin. Oncol. 2013;31:4188-98). Once childbearing has been completed or at the age of 40 years, a risk-reducing bilateral salpingo-oophorectomy (BSO) should be strongly considered (Gynecol. Oncol. 2009;113:6-11; Obstet. Gynecol. 2011;117:742-6).
In addition, patients with BRCA 1/2 mutations carry a 65%-74% lifetime risk of developing breast cancer (Gynecol. Oncol. 2009;113:6-11).ACOG recommends that these women begin screening for breast cancer at the age of 25 years through semiannual self-breast exams as well as annual mammography and breast MRI or sooner if a family member’s cancer was diagnosed prior to this age. Chemoprevention with tamoxifen also has been shown to reduce the risk of breast cancer in patients with BRCA2 disease, but is less effective for BRCA1 patients. Prophylactic mastectomy has the ability to reduce a woman’s risk of developing breast cancer by 90%-95%.
Hereditary nonpolyposis colorectal cancer syndrome
Another autosomal-dominant disorder, hereditary nonpolyposis colorectal cancer (HNPCC) syndrome arises as a result of a genetic defect in DNA mismatch repair mechanisms. Colon cancer is the most common malignancy associated with this syndrome, with a 70% risk by the age of 70 years (JAMA 2006;296:1507-17). Other associated cancers include those of the urinary tract, hepatobiliary tract, small intestine, skin, and brain, but strong supportive data are lacking. Beginning at age 20-25 years (or 10 years before the age of the youngest family member to develop colon cancer), a colonoscopy is recommended every 1-2 years. Annual urinalysis with cytology is advocated by some as a screening test for urinary tract cancers.
Patients with HNPCC have up to a 60% lifetime risk of endometrial cancer and a 10% risk of ovarian cancer (Int. J. Cancer 1999;81:214-8; Hum. Mol. Gene. 1997;6:105-10). The American Cancer Society recommends an endometrial biopsy and transvaginal ultrasonography annually between 30-35 years of age (JAMA 2006;296:1507-17). Schmeler et al. compared outcomes among 315 women with mismatch repair defects, 61 of whom underwent risk-reducing hysterectomy and BSO. With an average follow-up of greater than 7 years, none of the patients who underwent surgery developed cancer, while 33% of those who did not have surgery developed endometrial cancer and 5.5% developed ovarian cancer (N. Engl. J. Med. 2006;354:261-9). Because of these data, risk-reducing surgery at the age of 35 should be considered.
Cowden Syndrome
Cowden Syndrome, caused by an autosomal-dominant mutation in the PTEN gene, is associated with an up to 10% lifetime risk of endometrial cancer and a 50% risk of breast cancer (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). The NCCN notes that data are limited, but discussion of endometrial cancer symptoms should be encouraged (NCCN Guidelines Version 4, 2013). Annual endometrial sampling and ultrasound should be considered in woman aged 35-40 years or 10 years earlier than the youngest affected family member (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). Screening for breast cancer should include annual mammography and breast MRI starting between age 30-35 years or earlier depending on family history, per the NCCN guidelines.
It is important to note that additional genetic syndromes can have repercussions on the female genital tract, including the Li-Fraumeni (ovarian cancer), the Peutz-Jeghers (sex cord–stromal tumors of the ovary, granulosa cell tumors), and the Ollier (granulosa cell tumors) syndromes; unfortunately, screening guidelines for these rare syndromes have not been well studied (JAMA 2006;296:1507-17).
Dr. Schuler is a gynecologic oncologist at Good Samaritan Hospital in Cincinnati. Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig and Dr. Schuler said they had no relevant financial disclosures.