SUPPLEMENT TO SEPTEMBER 2014 This supplement is sponsored by Myriad Genetic Laboratories Incorporating hereditary cancer syndrome screening into daily practice Shari Goldman Snow, MD Assistant Professor of Clinical Obstetrics and Gynecology Northwestern University Feinberg School of Medicine Chicago, IL CASE 1 Managing fibroids—and cancer risk— JOIN THE FIGHT AGAINST HEREDITARY in a patient with BRCA1 mutation BREAST AND OVARIAN CANCER: ASSESS EVERY PATIENT AT EVERY VISIT YH is a 40-year-old patient, G0P0, who presented for a second • September is Ovarian Cancer Awareness Month opinion regarding large uterine fibroids. Her previous gyne- • October is Breast Cancer Awareness Month cologist treated the fibroids conservatively with medication • September 28–October 4 is Hereditary Breast and a dilation and curettage (D&C) procedure. The patient’s and Ovarian Cancer (HBOC) Awareness Week menorrhagia became severe, however, leading to anemia. A • October 1 is National Previvor Day* hysterectomy was recommended, but the patient wanted a second opinion to discuss options for preserving her uterus. *Previvor: An individual who carries a strong predisposition to cancer but has not developed the disease. YH’s personal history was significant for fibroids, a D&C, and a breast biopsy. Her family history revealed that a paternal aunt was diagnosed with breast cancer at age 50, another paternal aunt was diagnosed with ovarian cancer s gynecologists, every day we face an increasing at age 50, and a paternal cousin was diagnosed with breast number of clinical issues to consider when seeing cancer at age 30. The patient underwent genetic testing, A our patients. While we strive for comprehensiveness, and mutation of the breast and ovarian cancer susceptibil- it is important to stratify our patient care to prioritize life- ity gene, BRCA1, was identified. YH then decided against threatening risk factors. Identifying a pathogenic (deleteri- uterus-preserving options. She underwent robotic-assisted ous) hereditary cancer gene mutation allows the clinician to total laparoscopic hysterectomy and bilateral salpingo- implement life-saving, preventive management to reduce oophorectomy (BSO), as well as skin-sparing, nipple- cancer risk and improve early cancer detection. Knowing a sparing bilateral mastectomy and breast reconstruction, thus patient’s hereditary and familial cancer risk will drive gyneco- markedly decreasing her risk for ovarian and breast cancers. logic management and decision making. Without knowing a Identifying hereditary cancer syndromes in patients with a patient’s personal and/or family history of cancer, the clinician family history of cancer is imperative so appropriate surgical would be unable to determine appropriate treatment options options and alternatives can be discussed. Before undergo- for even the simplest gynecologic issue. Therefore, for every ing genetic testing, YH had been considering endometrial patient at every visit, it is imperative to systematically screen ablation, uterine artery embolization, myomectomy, and for personal and family risk of cancer and to test appropriate hysterectomy without BSO. None of those treatment options individuals for hereditary cancer syndromes. reduce the risk for ovarian and fallopian tube cancer—and The following cases illustrate how knowing a patient’s YH had up to a 44% risk of these cancers.1-5 hereditary cancer risk can affect the care we provide. CASE 2 Preconception testing helps direct screening during pregnancy Disclosure Dr. Snow reports that she is a consultant and speaker for Myriad Genetics AP, age 36, G1P0, presented with rectal bleeding at 28 weeks’ Laboratories. gestation. Her personal history is noncontributory. Family AVAILABLE AT WWW.OBGMANAGEMENT.COM September 2014 S1 HEREDITARY CANCER SYNDROME SCREENING TABLE 1 The American College of Obstetricians and Gynecologists recommends hereditary cancer risk assessment Family history as a risk assessment tool (Committee Opinion No. 478) • It is recommended that all women receive a family history evaluation as a screening tool for inherited risk. • Family history information should be reviewed and updated regularly, especially when there are significant changes to family history. Breast cancer screening (Practice Bulletin No. 122) • Risk assessment should be used to identify those who may qualify for enhanced screening, such as MRI screening, clinical breast examinations, and risk-reduction strategies. MRI, magnetic resonance image. Sources: American College of Obstetricians and Gynecologists. Family history as a risk assessment tool. Committee opinion No. 478. Obstet Gynecol. 2011;117(3):747-750; American College of Obstetricians and Gynecologists. Breast cancer screening. Practice bulletin No. 122. Obstet Gynecol. 2011;118(2 Pt 1): 372-382. history revealed that her maternal grandmother had uterine The patient underwent genetic testing, and a deleteri- cancer at age 42 and her maternal uncle was diagnosed with ous BRCA2 mutation was identified, permitting a thor- colon cancer at age 53. oughly informed discussion of the risks and benefits of Prior to her pregnancy, the patient underwent genetic various methods of contraception. LS opted to undergo testing and was found to have a deleterious TP53 mutation, laparoscopic supracervical hysterectomy and BSO. which placed her at increased risk for colon, uterine, Had LS’s genetic status been unknown, progesterone breast, and other cancers. She then had a colonoscopy, LARC and tubal occlusion via Essure or laparoscopic tubal endometrial biopsy, and mammography just prior to ligation would have been appropriate options; however, conception. Knowing that the colonoscopy was normal none of these methods offer the same benefit as BSO with 8 months prior to the patient’s rectal bleeding in pregnancy, regard to decreasing this patient’s risk of ovarian and fal- her physician performed a proctoscopy and diagnosed lopian tube cancer. Moreover, BSO would likely not have internal and external hemorrhoids, which were then been considered an option for LS in the absence of heredi- treated topically. tary cancer testing. An ObGyn clinician does not often evaluate rectal bleed- ing in an otherwise healthy, young pregnant woman; the CASE 4 Pelvic pain and dysmenorrhea: most common cause is hemorrhoids. Approximately 25% to Management influenced by genetic test results 35% of pregnant women experience hemorrhoids.6,7 In cer- JN is a 46-year-old woman, G3P3, who presented with pel- tain populations, up to 85% of pregnancies are affected by vic pain and dysmenorrhea. Ultrasonography revealed a hemorrhoids in the third trimester.8 If a patient has a family mildly enlarged uterus with findings suggestive of adeno- history of cancer, however, she may have a deleterious muta- myosis and normal adnexa. tion in one of a number of hereditary cancer genes, raising Her personal history consisted of 3 cesarean sections her risk for early onset of colon cancer. Given AP’s family his- and a remote history of endometrial ablation. Her family tory, without knowing her genetic information, colonoscopy history revealed that a paternal grandmother was diag- would not have been indicated prior to pregnancy. Knowing nosed with colon cancer at age 60 and with ovarian cancer genetic information helps identify which patients need to be at age 80. Her mother was diagnosed with colon cancer at evaluated for rectal bleeding to prevent or detect colon can- age 58. cer and, ideally, who should undergo screening colonoscopy The patient’s family history was suggestive of both prior to conception. hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome as well as a number of other heredi- CASE 3 Contraceptive choice guided tary cancer syndromes; she underwent hereditary cancer by identified cancer risk panel testing. A deleterious BRCA2 mutation was identi- LS, a 44-year-old woman, G1P1, presented to discuss con- fied, and results of the remainder of her hereditary cancer traceptive options. She was considering a progesterone panel testing were negative. long-acting reversible contraceptive (LARC), hysteroscopic JN opted to undergo robot-assisted total laparoscopic sterilization via tubal occlusion, and laparoscopic tubal hysterectomy and BSO, which relieved her pelvic pain. ligation. Without knowing that JN possessed a deleterious can- While her personal history was nonsignificant, her fam- cer mutation, management may have differed consider- ily history revealed that a maternal aunt was diagnosed ably. Treatment options may have included conservative with ovarian cancer at age 45, her maternal grandmother medical management or hysterectomy without BSO. Nei- was diagnosed with breast cancer at age 65, and her mother ther of these options would have significantly decreased was diagnosed with lung cancer at age 32. JN’s risk of ovarian and fallopian tube cancer. Occult ovar- S2 September 2014 ian and fallopian tube cancers are noted in 2% to 26% of TABLE 2 A simple office protocol BSO procedures performed in asymptomatic patients who for assessing hereditary cancer risk have a BRCA mutation.9-14 If BSO was performed with hys- 1) Screen terectomy without knowledge of JN’s genetic information, Capture a cancer family history with all patients at every visit washings would not have been performed, the specimen 2) Evaluate may have been morcellated, and the pathologist would not Review cancer family history using red flags have been alerted to thoroughly examine the specimen for occult cancer. Knowing