e110 VOL 130 NO 3 SEPTEMBER 2017 OBSTETRICS GYNECOLOGY - PDF document

e110 VOL. 130, NO. 3, SEPTEMBER 2017 OBSTETRICS & GYNECOLOGY tiple family members with breast cancer, ovarian cancer, or both. Based on the contemporary understanding of the screening and prevention strategies can be instituted to reduce their risks. Obstetrician–gynecologists play an important role in the identification and management of women with hereditary breast and ovarian cancer syndrome. If an obstetrician–gynecologist or other gynecologic care provider does not have the necessary knowledge or expertise in cancer syndrome, , but also will briefly discuss some of the other genes that have been implicated. 182, S 2017 (Replaces Practice Bulletin Number 103, April 2009) ACOG PRACTICE BULLETIN Clinical Management Guidelines for Obstetrician–Gynecologistsovarian cancer syndrome. Approximately 9–24% of process (). Individuals with hereditary breast and MutationsFrench Canadians, and Icelanders, among other groups. Hereditary Breast and Ovarian Cancer Syndrome The type of breast cancer also may vary based on progesterone negative, and -negative [also known are more commonly estrogen-receptor and progesterone-Risk of Ovarian Cancerian cancer (including fallopian tube cancer and primary mutations usually is high grade and has a and mutat

ions also have been found Other Hereditary Breast and Ovarian Cancer Syndrome MutationsIn addition to , other genes are impliThese other genes may account for up to 25% of herediovarian cancer, or both. The National Comprehensive Risk of Breast Cancer ). A meta-analysis of 10 studies that included a Table 1. Data from National Comprehensive Cancer Network. Genetic/familial high risk assessment: breast and ovarian. Version 2.2017. NCCN Hereditary Breast and Ovarian Cancer Syndrome history that includes first-degree and second-degree relation of the type of primary cancer, the age of onset, member. In addition, a patient’s ethnic background can ground is relevant in assessing a patient’s predisposition The American College of Obstetricians and Oncologists () have published guidance on the eleneal cancer can be transmitted through the father as well ), the National Society of Genetic Counselors (41), the National Comprehensive Care Network (17), and the Society of Gynecologic ) provide specific clinical criteria to assist would benefit from genetic counseling. The main crimore extensive genetic risk assessment and evaluaU.S. Preventive Services Task Force and the Agency distinct histologic phenotype that is predominantly ser- mutation. (2–5). Mucinous can

cer and Multiple pathologic studies of the fallopian tubes and who underwent risk-reducing salpingo-oophorectomy have identified cases of early microscopic high-grade Risk of Other Types of Cancercer. Additionally, mutation carriers have an investigation regarding the potential significant (but ovarian cancer. Evaluating a patient’s risk of hereditary Hereditary Breast and Ovarian Cancer Syndrome obstetrician–gynecologist (or other gynecologic care testing and identification of candidates in the family as the practical and ethical issues associated with of the results and discussion of management options such as intensive screening and risk-reduction interventions. Several online risk models are available to estimate a woman’s risk of developing breast cancer, gynecologic cancer, or both, and to help identify women who are candidates for genetic testing, intensive cancer screenBRCAPRO (available at www4.utsouthwestern.edu/), Tyrer–Cuzick or IBIS (available cea_home.html) (44–46). Two other risk prediction menarche, oral contraceptive pill use, history of tubal The possible outcomes of any genetic testing should be discussed as part of pretest genetic counseling and family remain unclear. If providing genetic testing, psychologic, reproduct

ive, and familial implications Box 1. Criteria for Further Genetic Evaluation for Hereditary Breast and Ovarian Cancer with breast cancer; ovarian, tubal, or peritoneal tubal, or peritoneal cancer and should receive genetic half-sibling), or third degree (first cousin, great-grandparent or great-assessment for inherited gynecologic cancer predispositions.SGO Hereditary Breast and Ovarian Cancer Syndrome www.sgo.org/genetics/genetics-cologic Oncology, the American College of Obstetricians and Gynecologists, the National Society of Genetic Counselors, Bright Pink, and Facing Our Risk of Cancer Empowered (FORCE). The American College of Obstetricians and Gynecologists’ genetics web page www.acog.org/Genetics) and Committee Opinion No. 693, Counseling About Genetic Testing and Com-, include additional guidance and information on the clinical and ethical issues related to genetic testing in gynecologic practice. genetic counseling suggest the presence of an inherited Mutation Testingtargeted multisite mutation testing, comprehensive gene sequencing, and rearrangement testing (49). If a specific mutation is identified in an affected other potential implications of genetic testing, such as cost, privacy, and insurance coverage. Medicare and ment discrimination

based on genetic information (Many states also have laws that provide similar protecCommon clinical and ethical issues regarding care are presented and addressed in a case format in Box 2. Possible Outcomes of Mutation* Testing Hereditary Breast and Ovarian Cancer Syndrome proved to decrease the mortality rate or increase the the risk of ovarian cancer algorithm) every 4 months and annual transvaginal ultrasonography (55). Risk-reducing Risk-Reducing Agents). Given the magnitude of the potential benefits (eg, ovar Multigene Panel TestingTechnologic advances in genetic sequencing have resulted in the ability to perform parallel sequencing of ics expertise and after genetic counseling and informed account for most cases of hereditary breast and ovarian cancer, other genes have been found to be associated with this hereditary syndrome (Table 1), and results showing mutations in such genes may affect patient counseling regarding screening and risk-reductionresults and how this affects interpretation, patient counno) data on associated cancer risk to guide appropriate management (17). Health care providers who order these How should women with mutations in BRCA1 or BRCA2 be counseled to reduce the risk of ovarian cancer?Current strategies to reduce the risk of develop

ing ovar- Hereditary Breast and Ovarian Cancer Syndrome mutations, the risk of ovarian cancer markwoman’s desire to preserve fertility or prevent premature Bilateral salpingectomy alone in high-risk women is not ectomy as an option for women with mutations. to avoid the adverse effects of early menopause that benefit of reducing breast cancer risk, which is an imporPopulation data for women at average risk confirm a trials are still ongoing for high-risk women. One study intended solely for ovarian cancer risk reduction remains prevention, cycle regulation), it is appropriate for women with mutations in or to use oral contraSurgical Risk Reductionoophorectomy be considered for those with Lynch syneral salpingo-oophorectomy reduces the risk of ovarby approximately 80% (hazard ratio, 0.21; 95% CI, ). In addition, risk-reducing bilateral toms of early menopause (eg, vasomotor symptoms and childbearing, and family history. Typically, risk-reducing consider delaying until age 40–45 years because of be diagnosed in less than 2–3% of women with Hereditary Breast and Ovarian Cancer Syndrome after tamoxifen use among the general population (riers (75). This likely reflects the lower prevalence (10–24%) of estrogen receptor-positive breast canIn a sys

tematic review and meta-analysis of pubpub–)women randomized to placebo. In the only head-to-head trial in the analysis, tamoxifen was associated with a greater risk reduction than raloxifene (RR of invasive cancer for raloxifene, 1.24; 95% CI, 1.05–1.47). Both medications were associated with a decreased risk of (discharge, itching, dryness, and dyspareunia) (77). thromboembolic events (RR, 1.93; 95% CI, 1.41–2.64) Risk-Reducing Surgerymastectomy. Bilateral mastectomy reduces the risk of increased surveillance with more intensive breast cancer mutations, recommended breast cancer surveillance and annual radiographic screening (preferably, magmag)()Magnetic resonance imaging of the breast with contrast is preferred over annual mammography from ages 25–29 has the highest sensitivity for the detection of breast can mutation carriers) include false-positive discomfort, pain, and anxiety (49). Systematic review Risk-Reducing Agents Hereditary Breast and Ovarian Cancer Syndrome cancer risk associated with risk-reducing bilateral patient and physician preference and the availability of an experienced health care provider to perform adequate fallopian tube should be divided at its insertion into the can be placed in an endoscopic bag before removal from ci

es found at risk-reducing salpingo-oophorectomy are lopian tubes is necessary, with microscopic examination ovary or fallopian tube has been identified in have been no trials that compared the efficacy of the two methods. Consideration of a contralateral prophymutation carriers with breast cancer, given the 30% risk sidering prophylactic mastectomy is important and as well as the short-term and long-term complications cancer (). Commonly reported adverse psychosocial Risk-reducing bilateral salpingo-oophorectomy for ovar-positive women with breast cancer (if patients are premenopausal at the time of risk-reducing associated with prevention of premenopausal breast Hereditary Breast and Ovarian Cancer Syndrome of estrogen-only or combination hormone therapy for a risk reduction in the patient who is premenopausal at time of risk-reducing salpingo-oophorectomy is not about symptom awareness and a discussion of the need There have been contradictory reports on whether mutations, without a history of cancer and who have not dence suggests that mutation carriers may have often is affected because many women with mutaMenopausal symptoms, including hot flushes, sexual discomfort (resulting from vaginal atrophy), and reduced libido are common in women who have fallopia

n tubes is critical in order to detect microscopic ally sectioned and evaluated (91). In fact, more cases of than microscopic ovarian cancer in the prophylactic risk-identified are microscopic, they are often high grade, and information from the peritoneal lavage may reflect actually represents the recurrence of a previously unrec). However, benefits of hysterectomy include a more simplified hormone therapy strategy (with estrogen be considered when there are other medical indications for removal of the uterus and cervix. For women taking undergo risk-reducing salpingo-oophorectomy by the and may have long-term health outcomes of heart Hereditary Breast and Ovarian Cancer Syndrome pian tube cancer or primary peritoneal cancer) and actionable deleterious mutation that is predisposing to breast cancer should be offered risk-reducing actionable deleterious mutation predisposing to ovarian cancer should be offered risk-reducing bilateral salpingo-oophorectomy. The timing of salpingo-oophorectomy is recommended at age may consider delaying until age 40–45 years For a risk-reducing bilateral salpingo-oophorectomy, all tissue from the ovaries and fallopian tubes The following recommendations are based primar ovarian cancer syndrome should be a routine part of uation

should include a personal medical history Genetic testing is recommended when the results of inherited cancer syndrome for which specific genes includes both and other genetic mutations. cancer syndrome or when a patient has a personal or undergone risk-reducing salpingo-oophorectomy. For of-life studies of high-risk women who have undergone or ovarian cancer-associated gene should be managed associated genes (Table 1), although there may be other women tested before 2013 would not have had access to to clarify their residual risk and the need for additional contact with clinicians experienced in the care of women with ovarian epithelial cancer (this includes fallo Hereditary Breast and Ovarian Cancer Syndrome Jewish population frequencies for common mutations ing for hereditary breast-ovarian cancer [published Cancer analysis of BRCA1 and BRCA2 mutations in American JAMA 17. JE, Hopper JL, et al. Average risks of breast and ovarian sonal or family history of ovarian cancer, routine ovarian cancer screening with measurement of generally is not recommended. Transvaginal ultrasonography or measurement of serum CA 125 level risk-reducing bilateral salpingo-oophorectomy, which is the only proven intervention to reduce For women aged 25–29 years with known B

RCA lance includes clinical breast examination every For women aged 30 years and older with known mutations or other actionable breast cancer breast or ovarian cancer but who do not have a American College of Obstetricians and Gynecologists. Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, et al. Mutations in 12 genes for inherited CC, Rendi MH, et al. Germline and somatic mutations in homologous recombination genes predict platinum Hereditary Breast and Ovarian Cancer Syndrome cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: family history: appears in Am J Hum Genet 2003;73:709]. Am J Hum Genet 2003;72:1117–30. (Meta-Analysis)    20.    King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2.New York Breast Cancer Study Group. mutations in unselected patients with triple receptor-Berchuck A, Heron KA, Carney ME, Lancaster JM, JAMA Yates MS, Meyer LA, Deavers MT, Daniels MS, Keeler covered during risk reduction salpingo-oophorectomy in CL, Dao F, et al. Clinical outcome of isolated serous 33. Powell CB, Chen LM, McLennan J, Crawford B, oophorectomy (RRSO) in BRCA mutation carriers: using a standardized surgical-path

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abase, the Cochrane Library, and to conduct a litture search to locate relvant arpubtween January 2000 and May 2017. The search guage. nal search, although review arcles and comies also sia and sciic cones were not conered adequate lished by tions or intions such as the Naal Intutes cians and gists were reviewed, and adal studies were liographies of identified articles. able research was not available, expert opinions from obcian–gynecologists were used.Evidence obtained from at least one properlytrolled Evidence obtained from well-designed cohort or bly from more Evidence obtained from multiple time series with or ments also could be regarded as this type of evcal ence, descriptive studies, or reports of expert tent sciic evidence.cians and Gynecologists. All rights reserved. No part of this tem, posted on the Internet, or transmitted, in any form or by any means, elecic, mecal, photocopying, recording, ordirected to Copyright Clearance Center, 222 Rosewood Drive, Gynecol 2017:130:e110–26. of this information is voluntary. ndard of care. It is not intended , in the reasonable judgment es, or advances in knowledge or ns may not reflect the most recent evidence.Any updates to this document can be found on firm, organization, or person. ect to any liabilitie