No. 366-Gynaecologic Management of Hereditary Breast and Ovarian Cancer

Abstract

Objective: This Committee Opinion outlines the gynaecologic management recommendations for women diagnosed with hereditary breast and ovarian cancer syndrome (HBOC) with respect to screening, contraception, chemoprophylaxis, fertility considerations, risk-reducing surgery, and post-oophorectomy care. Intended Users: This Committee Opinion is designed for gynaecologic oncologists, general gynaecologists, family physicians, genetic counsellors, registered nurses, nurse practitioners, residents, and health care providers. Target Population: Adult women (18 years and older) with a pathogenic germline variant in the BRCA1, BRCA2, and other ovarian cancer–associated genes. Evidence: While reviewing evidence, databases searched include Medline, Cochrane, and PubMed. Medical Subject Heading search terms used include BRCA AND gynaecology management, hormone replacement therapy, risk reduction, chemoprophylaxis, fertility from 01/2010 and 10/2017. Literature search was begun 07/2017 and finalized 10/2017. In total 183 studies were identified, and 101 were used. Validation Methods: The content and recommendations were drafted and agreed upon by the principal authors. The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework (Table 1). The interpretation of strong and conditional (weak) recommendations is described in Table 2. The Summary of Findings is available upon request. Benefits, Harms, and Costs: We may expect a risk reduction of up to 90% in women predisposed to HBOC who undergo risk-reducing bilateral salpingo-oophorectomy. The harms of iatrogenic premature menopause are offset by the benefits of risk reduction. By minimizing potential tubal/ovarian/peritoneal cancers, we can expect savings to the health care system. Guideline Update: Evidence will be reviewed 5 years after publication to decide whether all or part of the opinion should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. Sponsors: This guideline was developed with resources funded by the Society of Obstetricians and Gynaecologists of Canada. Recommendations: 1 Patients identified by their gynaecologist, primary care physician, medical geneticist, or oncologist as being at high risk for hereditary breast ovarian cancer according to the National Comprehensive Cancer Network or their respective provincial criteria should be offered genetic counselling and assessment. Patients should be thoroughly counselled on the results and implications of their testing by an expert in genetics (strong, high).2 Patients with a strong clinical suspicion for hereditary breast ovarian cancer and uninformative or variant of unknown clinical significance testing should be seen every 5 years by genetics (strong, moderate).3 There is currently insufficient data to support ovarian/tubal/peritoneal cancer screening.4 Risk-reducing surgery according to established guidelines (Table 3) is the most effective way to reduce the risk of ovarian cancer in women with a hereditary predisposition or risk (strong, low).5 Breastfeeding appears to be protective in BRCA1 carriers. There are insufficient data for BRCA2 (conditional, moderate).6 Optimal breast screening is delayed by lactational changes, and decisions on duration of breastfeeding should be made on an individualized basis (strong, high).7 BRCA carriers of pathogenic variants undergoing gonadotoxic or hormone-based breast cancer treatment should have an urgent consultation with reproductive endocrine and infertility specialists if fertility is a concern and child-bearing is not complete (strong, high).8 BRCA1 carriers are recommended to undergo risk-reducing salpingo-oophorectomy during child-bearing age and should consider this when family planning (strong, high).9 BRCA mutation carriers affected by infertility can safely undergo fertility treatments (strong, moderate).10 The option to screen preimplantation for embryos harbouring a pathogenic variant is available in Canada and should be discussed with all carriers, regardless of fertility (strong, high).11 Combined hormonal contraceptive use is an effective method of chemoprevention for ovarian/tubal/peritoneal cancer in the general population and women with BRCA1/2 (strong, high).12 The use of CHCs in young BRCA1 variant carriers should be individualized, taking into account the risks and benefits (strong, moderate).13 It is premature to recommend ASA for ovarian cancer prophylaxis in the BRCA carrier population (conditional, low).14 Risk-reducing salpingo-oophorectomy should be offered to BRCA1 carriers between 35 and 40 years of age and BRCA2 carriers from between 40 and 45 years for ovarian/tubal/peritoneal carcinoma risk reduction (strong, high).15 For women diagnosed as pathogenic variant carriers postmenopausally, risk-reducing salpingo-oophorectomy should be offered upon diagnosis (strong, high).16 Risk-reducing salpingo-oophorectomy should be considered for breast cancer risk reduction in BRCA2 mutation carriers under 50 years (strong, moderate).17 After a breast cancer diagnosis, risk-reducing salpingo-oophorectomy for breast cancer mortality reduction should be considered within 2 years to BRCA1 carriers, and for BRCA2 carriers as part of their breast cancer treatment if considered appropriate by their oncologist (strong, high).18 Bilateral salpingectomy alone for ovarian/tubal/peritoneal cancer risk reduction in BRCA variant carriers is still under investigation and should only be offered as an alternative to risk-reducing salpingo-oophorectomy under a research protocol or if risk-reducing salpingo-oophorectomy is an unacceptable choice for the patient (strong, low).19 Bilateral salpingectomy is an option for BRCA variant carriers who are younger than the recommended age for risk-reducing salpingo-oophorectomy and do not wish to conceive further pregnancies (without assisted reproductive technologies) (strong, high).20 The inclusion of hysterectomy with risk-reducing salpingo-oophorectomy for BRCA variant carriers should be individualized, taking into account risk factors for uterine cancer, other uterine pathology, and tamoxifen use (strong, moderate).21 There are insufficient data to routinely recommend hysterectomy to reduce the risk of papillary serous uterine cancer in BRCA1 mutation carriers (conditional, low).22 All risk-reducing salpingo-oophorectomy for BRCA variant carriers should be performed by a skilled gynaecologist/gynaecologic oncologist familiar with the technique described. It is imperative that specimens be examined by an experienced pathologist familiar with optimal specimen processing and diagnostic criteria. Should an invasive or occult carcinoma be found, patients should be referred to a gynaecologic oncologist (strong, high).23 In the absence of contraindications, premenopausal BRCA1/2 carriers undergoing risk-reducing salpingo-oophorectomy should be offered hormone therapy until the average age of menopause (strong, high).24 Women with a history of breast cancer can be offered nonhormonal alternatives for vasomotor symptom management (strong, moderate).25 Local vaginal estrogen therapy can be considered in all women suffering from genitourinary syndrome of menopause, but nonhormonal alternatives are recommended first in women with a personal history of breast cancer, especially those on aromatase inhibitors (strong, moderate).26 Post-oophorectomy care should be administered in an individualized manner, ensuring optimal quality of life, bone health, and cardiovascular risk amelioration (strong, moderate).27 Following RRSO, it is not recommended to do surveillance for peritoneal cancer in BRCA mutation carriers (conditional, moderate).