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JOGC

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).

      Key Words

      Abbreviations:

      ASA (acetylsalicylic acid), CA (125 cancer antigen 125), CHC (combined hormonal contraceptive), CI (confidence interval), GSM (genitourinary syndrome of menopause), HBOC (hereditary breast ovarian cancer), HR (hazard ratio), HT (hormone therapy), IVF (in vitro fertilization), NCCN (National Comprehensive Cancer Network), OR (odds ratio), PGD (pre-implantation genetic diagnosis), RCT (randomized controlled trial), RRSO (risk-reducing salpingo-oophorectomy), TVUS (transvaginal ultrasound), VUS (variant of unknown clinical significance)
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      References

        • Daly MB
        • Pilarski R
        • Berry M
        • et al.
        NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017.
        J Natl Compr Canc Netw. 2017; 15: 9-20
        • Committee on Practice Bulletins–Gynecology, Committee on Genetics, Society of Gynecologic Oncology
        Practice bulletin no 182: hereditary breast and ovarian cancer syndrome.
        Obstet Gynecol. 2017; 130: e110-e126
        • Fackenthal JD
        • Olopade OI
        Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations.
        Nat Rev Cancer. 2007; 7: 937-948
        • Hall MJ
        • Reid JE
        • Burbidge LA
        • et al.
        BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer.
        Cancer. 2009; 115: 2222-2233
        • Antoniou A
        • Pharoah PDP
        • Narod S
        • et al.
        Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies.
        Am J Hum Genet. 2003; 72: 1117-1130
        • Norquist BM
        • Harrell MI
        • Brady MF
        • et al.
        Inherited mutations in women with ovarian carcinoma.
        JAMA Oncol. 2016; 2: 482-490
        • King M-C
        • Marks JH
        • Mandell JB
        • et al.
        Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2.
        Science. 2003; 302: 643-646
        • Risch HA
        • McLaughlin JR
        • Cole DEC
        • et al.
        Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer.
        Am J Hum Genet. 2001; 68: 700-710
        • Buys SS
        • Sandbach JF
        • Gammon A
        • et al.
        A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes.
        Cancer. 2017; 123: 1721-1730
        • Kuchenbaecker KB
        • Hopper JL
        • Barnes DR
        • et al.
        Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
        JAMA. 2017; 317: 2402-2416
        • Ford D
        • Easton DF
        The genetics of breast and ovarian cancer.
        Br J Cancer. 1995; 72: 805-812
        • Chen S
        • Parmigiani G
        Meta-analysis of BRCA1 and BRCA2 penetrance.
        J Clin Oncol. 2007; 25: 1329-1333
        • Metcalfe KA
        • Lynch HT
        • Ghadirian P
        • et al.
        The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers.
        Gynecol Oncol. 2005; 96: 222-226
        • Ibarra JA
        Pathology of BRCA tumors.
        in: Chagpar AB Managing BRCA Mutation Carriers. Springer, XXX, XX2017: 89-117
        • Nelson HD
        • Fu R
        • Goddard K
        • et al.
        Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation.
        Agency for Healthcare Research and Quality, Rockville, MD2014
      1. Surveillance, Epidemiology, and End Results Program, National Cancer Institute. Ovarian Cancer: Cancer Stat Facts. Available at: https://seer.cancer.gov/statfacts/html/ovary.html. Accessed on June 18, 2018.

        • Rosenthal AN
        • Fraser L
        • Manchanda R
        • et al.
        Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule.
        J Clin Oncol. 2013; 31: 49-57
        • Buys SS
        • Partridge E
        • Black A
        • et al.
        Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening randomized controlled trial.
        JAMA. 2011; 305: 2295-2303
        • The Lancet
        UKCTOCS and the evaluation of screening for ovarian cancer.
        Lancet. 2016; 387: 918
        • Rosenthal AN
        • Fraser LSM
        • Philpott S
        • et al.
        Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the United Kingdom familial ovarian cancer screening study.
        J Clin Oncol. 2017; 35: 1411-1420
        • Cortesi L
        • De Matteis E
        • Toss A
        • et al.
        Evaluation of transvaginal ultrasound plus CA-125 measurement and prophylactic salpingo-oophorectomy in women at different risk levels of ovarian cancer: the Modena Study Group Cohort Study.
        Oncology. 2017; 93: 377-386
        • Kotsopoulos J
        • Lubinski J
        • Salmena L
        • et al.
        Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
        Breast Cancer Res. 2012; 14: R42
        • Cullinane CA
        • Lubinski J
        • Neuhausen SL
        • et al.
        Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers.
        Int J Cancer. 2005; 117: 988-991
        • Vashi R
        • Hooley R
        • Butler R
        • et al.
        Breast imaging of the pregnant and lactating patient: physiologic changes and common benign entities.
        AJR Am J Roentgenol. 2013; 200: 329-336
        • Finch A
        • Valentini A
        • Greenblatt E
        • et al.
        Frequency of premature menopause in women who carry a BRCA1 or BRCA2 mutation.
        Fertil Steril. 2013; 99: 1724-1728
        • Oktay K
        • Kim JY
        • Barad D
        • et al.
        Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks.
        J Clin Oncol. 2010; 28: 240-244
        • Phillips K-A
        • Collins IM
        • Milne RL
        • et al.
        Anti-müllerian hormone serum concentrations of women with germline BRCA1 or BRCA2 mutations.
        Obstet Gynecol Surv. 2016; 71: 474-475
        • Turan V
        • Moy F
        • Oktay KH
        Association of germline BRCA mutations with impaired fertility preservation cycle outcomes.
        Fertil Steril. 2017; 108: e187-e188
        • Practice Committee of American Society for Reproductive Medicine
        Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion.
        Fertil Steril. 2013; 100: 1214-1223
        • Valentini A
        • Finch A
        • Lubinski J
        • et al.
        Chemotherapy-induced amenorrhea in patients with breast cancer with a BRCA1 or BRCA2 mutation.
        J Clin Oncol. 2013; 31: 3914-3919
        • de la Noval BD
        Potential implications on female fertility and reproductive lifespan in BRCA germline mutation women.
        Arch Gynecol Obstet. 2016; 294: 1099-1103
        • Lambertini M
        • Del Mastro L
        Fertility preservation in BRCA-mutated breast cancer patients.
        Breast Cancer Manag. 2016; 5: 61-68
        • Lambertini M
        • Poggio F
        • Vaglica M
        • et al.
        News on the medical treatment of young women with early-stage HER2-negative breast cancer.
        Expert Opin Pharmacother. 2016; 17: 1643-1655
        • Regan MM
        • Walley BA
        • Francis PA
        • et al.
        Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.
        Ann Oncol. 2017; 28: 2225-2232
      2. Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer (POSITIVE). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02308085. Accessed on June 18, 2018.

        • Wilkinson E
        Preimplantation genetic diagnosis for mutated BRCA genes.
        Lancet Oncol. 2012; 13: e331
        • Kotsopoulos J
        • Librach CL
        • Lubinski J
        • et al.
        Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: a case-control study.
        Cancer Causes Control. 2008; 19: 1111-1119
        • Shapira M
        • Raanani H
        • Feldman B
        • et al.
        BRCA mutation carriers show normal ovarian response in in vitro fertilization cycles.
        Fertil Steril. 2015; 104: 1162-1167
        • Gietel-Habets JJG
        • de Die-Smulders CEM
        • et al.
        Awareness and attitude regarding reproductive options of persons carrying a BRCA mutation and their partners.
        Hum Reprod. 2017; 32: 588-597
        • Derks-Smeets IAP
        • Gietel-Habets JJG
        • Tibben A
        • et al.
        Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer.
        Hum Reprod. 2014; 29: 1103-1112
        • Menon U
        • Harper J
        • Sharma A
        • et al.
        Views of BRCA gene mutation carriers on preimplantation genetic diagnosis as a reproductive option for hereditary breast and ovarian cancer.
        Hum Reprod. 2007; 22: 1573-1577
        • Figueiredo JC
        • Haile RW
        • Bernstein L
        • et al.
        Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study.
        Breast Cancer Res Treat. 2010; 120: 175-183
        • Cibula D
        • Zikan M
        • Dusek L
        • et al.
        Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis.
        Expert Rev Anticancer Ther. 2011; 11: 1197-1207
        • Narod SA
        • Dubé MP
        • Klijn J
        Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
        J Natl Cancer Inst. 2002; 94: 1773-1779
        • Modan B
        • Hartge P
        • Hirsh-Yechezkel G
        • et al.
        Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation.
        N Engl J Med. 2001; 345: 235-240
        • Moorman PG
        • Havrilesky LJ
        • Gierisch JM
        • et al.
        Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis.
        J Clin Oncol. 2013; 31: 4188-4198
        • Trabert B
        • Ness RB
        • Lo-Ciganic W-H
        • et al.
        Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium.
        J Natl Cancer Inst. 2014; 106 (djt431)
        • Baandrup L
        • Kjaer SK
        • Olsen JH
        • et al.
        Low-dose aspirin use and the risk of ovarian cancer in Denmark.
        Ann Oncol. 2015; 26: 787-792
      3. Canadian Cancer Trials Group. Gynecologic Disease Site. Available at: https://www.ctg.queensu.ca/public/gynecologic/gynecologic-disease-site. Accessed on June 18, 2018.

        • Rebbeck TR
        • Kauff ND
        • Domchek SM
        Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers.
        J Natl Cancer Inst. 2009; 101: 80-87
        • Kotsopoulos J
        • Huzarski T
        • Gronwald J
        • et al.
        Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers.
        J Natl Cancer Inst. 2016; 109 (djw177)
        • Kauff ND
        • Domchek SM
        • Friebel
        • et al.
        Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study.
        J Clin Oncol. 2008; 26: 1331-1337
        • Finch A
        • Metcalfe KA
        • Chiang J
        • et al.
        The impact of prophylactic salpingo-oophorectomy on quality of life and psychological distress in women with a BRCA mutation.
        Psychooncology. 2011; 22: 212-219
        • Finch A
        • Narod SA
        Quality of life and health status after prophylactic salpingo-oophorectomy in women who carry a BRCA mutation: a review.
        Maturitas. 2011; 70: 261-265
        • Domchek SM
        • Friebel TM
        • Singer CF
        • et al.
        Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
        JAMA. 2010; 304: 967-975
        • Brose MS
        • Rebbeck TR
        • Calzone KA
        • et al.
        Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program.
        J Natl Cancer Inst. 2002; 94: 1365-1372
        • Metcalfe K
        • Lynch HT
        • Foulkes WD
        • et al.
        Effect of oophorectomy on survival after breast cancer in BRCA1 and BRCA2 mutation carriers.
        JAMA Oncol. 2015; 1: 306-313
        • Huzarski T
        • Byrski T
        • Gronwald J
        • et al.
        Ten-year survival in patients with BRCA1-negative and BRCA1-positive breast cancer.
        J Clin Oncol. 2013; 31: 3191-3196
        • Valentini A
        • Lubinski J
        • Byrski T
        • et al.
        The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation.
        Breast Cancer Res Treat. 2013; 142: 177-185
        • Piek JMJ
        • Verheijen RHM
        • Kenemans P
        • et al.
        BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis.
        Gynecol Oncol. 2003; 90: 491
        • Kurman RJ
        • Shih I-M
        The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory.
        Am J Surg Pathol. 2010; 34: 433-443
        • Zakhour M
        • Danovitch Y
        • Lester J
        • et al.
        Occult and subsequent cancer incidence following risk-reducing surgery in BRCA mutation carriers.
        Gynecol Oncol. 2016; 143: 231-235
        • Conner JR
        • Meserve E
        • Pizer E
        • et al.
        Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo-oophorectomy in women with germ-line BRCA1 or BRCA2 mutations.
        Gynecol Oncol. 2014; 132: 280-286
        • Powell CB
        • Swisher EM
        • Cass I
        • et al.
        Long term follow up of BRCA1 and BRCA2 mutation carriers with unsuspected neoplasia identified at risk reducing salpingo-oophorectomy.
        Gynecol Oncol. 2013; 129: 364-371
      4. Harmsen MG, Arts-de Jong M, Hoogerbrugge N, et al. Early salpingectomy (tubectomy) with delayed oophorectomy to improve quality of life as alternative for risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers (TUBA study): a prospective non-randomised multicentre study. BMC Cancer. 201519;15:593.

        • Falconer H
        • Yin L
        • Grönberg H
        • et al.
        Ovarian cancer risk after salpingectomy: a nationwide population-based study.
        J Natl Cancer Inst. 2015; 107 (dju410)
        • Harmsen MG
        • IntHout J
        • Arts-de Jong M
        • et al.
        Salpingectomy with delayed oophorectomy in BRCA1/2 mutation carriers: estimating ovarian cancer risk.
        Obstet Gynecol. 2016; 127: 1054-1063
        • Segev Y
        • Iqbal J
        • Lubinski J
        • et al.
        The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: an international prospective cohort study.
        Gynecol Oncol. 2013; 130: 127-131
        • Beiner ME
        • Finch A
        • Rosen B
        • et al.
        The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations.
        A prospective study. Gynecol Oncol. 2007; 104: 7-10
        • Shu CA
        • Pike MC
        • Jotwani AR
        • et al.
        Uterine cancer after risk-reducing salpingo-oophorectomy without hysterectomy in women with BRCA mutations.
        JAMA Oncol. 2016; 2: 1434-1440
        • Vyarvelska I
        • Rosen B
        • Narod SA
        Should hysterectomy complement prophylactic salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers.
        Gynecol Oncol. 2014; 134: 219-221
        • Colgan TJ
        • Boerner SL
        • Murphy J
        • et al.
        Peritoneal lavage cytology: an assessment of its value during prophylactic oophorectomy.
        Gynecol Oncol. 2002; 85: 397-403
        • Cass I
        • Walts A
        • Karlan BY
        Does risk-reducing bilateral salpingo-oophorectomy leave behind residual tube.
        Gynecol Oncol. 2010; 117: 27-31
        • Walker JL
        • Powell CB
        • Chen L-M
        • et al.
        Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer.
        Cancer. 2015; 121: 2108-2120
        • George SHL
        • Garcia R
        • Slomovitz BM
        Ovarian cancer: the fallopian tube as the site of origin and opportunities for prevention.
        Front Oncol. 2016; 6: 108
        • Cass I
        • Holschneider C
        • Datta N
        • et al.
        BRCA-mutation–associated fallopian tube carcinoma.
        Obstet Gynecol. 2005; 106: 1327-1334
        • Rabban JT
        • Krasik E
        • Chen L-M
        • et al.
        Multistep level sections to detect occult fallopian tube carcinoma in risk-reducing salpingo-oophorectomies from women with BRCA mutations: implications for defining an optimal specimen dissection protocol.
        Am J Surg Pathol. 2009; 33: 1878-1885
        • Powell CB
        • Chen L-M
        • McLennan J
        • et al.
        Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers: experience with a consecutive series of 111 patients using a standardized surgical-pathological protocol.
        Int J Gynecol Cancer. 2011; 21: 846-851
        • Reitsma W
        • de Bock GH
        • Oosterwijk JC
        • et al.
        Support of the “fallopian tube hypothesis” in a prospective series of risk-reducing salpingo-oophorectomy specimens.
        Eur J Cancer. 2013; 49: 132-141
        • The NAMS 2017 Hormone Therapy Position Statement Advisory Panel
        The 2017 hormone therapy position statement of The North American Menopause Society.
        Menopause. 2017; 24: 728-753
        • Guidozzi F
        • Daponte A
        Estrogen replacement therapy for ovarian carcinoma survivors: a randomized controlled trial.
        Cancer. 1999; 86: 1013-1018
        • Kotsopoulos J
        • Lubinski J
        • Neuhausen SL
        • et al.
        Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.
        Gynecol Oncol. 2006; 100: 83-88
        • Eisen A
        • Lubinski J
        • Gronwald J
        • et al.
        Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers.
        J Natl Cancer Inst. 2008; 100: 1361-1367
        • Kotsopoulos J
        • Huzarski T
        • Gronwald J
        • et al.
        Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study.
        Breast Cancer Res Treat. 2016; 155: 365-373
        • Rebbeck TR
        • Friebel T
        • Wagner T
        • et al.
        Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.
        J Clin Oncol. 2005; 23: 7804-7810
        • Finch A
        • Metcalfe KA
        • Chiang JK
        • et al.
        The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation.
        Gynecol Oncol. 2011; 121: 163-168
        • Madalinska JB
        • van Beurden M
        • Bleiker EMA
        • et al.
        The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy.
        J Clin Oncol. 2006; 24: 3576-3582
        • Elit L
        • Esplen MJ
        • Butler K
        • et al.
        Quality of life and psychosexual adjustment after prophylactic oophorectomy for a family history of ovarian cancer.
        Fam Cancer. 2001; 1: 149-156
        • Dennerstein L
        • Alexander JL
        Estradiol and sexual function in postmenopausal women.
        Menopause. 2006; 13: 721-723
        • Fang CY
        • Cherry C
        • Devarajan K
        • et al.
        A prospective study of quality of life among women undergoing risk-reducing salpingo-oophorectomy versus gynecologic screening for ovarian cancer.
        Gynecol Oncol. 2009; 112: 594-600
        • Cohen JV
        • Chiel L
        • Boghossian L
        • et al.
        Non-cancer endpoints in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy.
        Fam Cancer. 2012; 11: 69-75
        • Michelsen TM
        • Pripp AH
        • Tonstad S
        • et al.
        Metabolic syndrome after risk-reducing salpingo-oophorectomy in women at high risk for hereditary breast ovarian cancer: a controlled observational study.
        Eur J Cancer. 2009; 45: 82-89
        • Chapman JS
        • Powell CB
        • McLennan J
        • et al.
        Surveillance of survivors: follow-up after risk-reducing salpingo-oophorectomy in BRCA 1/2 mutation carriers.
        Gynecol Oncol. 2011; 122: 339-343
        • Brincat M
        • Muscat Baron Y
        • Ciantar E
        Hormone replacement in women with breast cancer: the HABITS study.
        Endocrine. 2004; 24: 255-258
        • Rutqvist LE
        • Johansson H
        • on behalf of the Stockholm Breast Cancer Study Group
        Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer.
        Acta Oncol. 2007; 46: 133-145
        • Leon-Ferre RA
        • Majithia N
        • Loprinzi CL
        Management of hot flashes in women with breast cancer receiving ovarian function suppression.
        Cancer Treat Rev. 2017 Jan; 52: 82-90
        • Chilcot J
        • Norton S
        • Hunter MS
        Cognitive behaviour therapy for menopausal symptoms following breast cancer treatment: who benefits and how does it work.
        Maturitas. 2014 May; 78: 56-61
        • Levine DA
        • Argenta PA
        • Yee CJ
        • Marshall DS
        • Olvera N
        • Bogomolniy F
        • et al.
        Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations.
        J Clin Oncol. 2003 Nov 15; 21: 4222-4227
        • Finch A
        Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation.
        JAMA. 2006; 296: 185
        • Iavazzo C
        • Gkegkes ID
        • Vrachnis N
        Primary peritoneal cancer in BRCA carriers after prophylactic bilateral salpingo-oophorectomy.
        J Turk Ger Gynecol Assoc. 2016 Jan 12; 17: 73-76