Pathologic findings at risk-reducing salpingo-oophorectomy: primary results from Gynecologic Oncology Group Trial GOG-0199.

PURPOSE Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study. PARTICIPANTS AND METHODS This analysis included asymptomatic high-risk women age ≥ 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participant's mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression. RESULTS Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P < .001) were associated with detection of clinically occult neoplasms at RRSO. For 387 women with negative BRCA1/2 mutation testing and normal CA-125 levels, findings at RRSO were benign. CONCLUSION Clinically occult cancer was detected among 2.6% of high-risk women undergoing RRSO. BRCA1/2 mutation, postmenopausal status, and abnormal preoperative CA-125 and/or TVU were associated with cancer detection at RRSO. These data can inform management decisions among women at high risk of ovarian/tubal cancer.

[1]  S. Friedman,et al.  Genetic/familial high-risk assessment: breast and ovarian, version 1.2014. , 2014, Journal of the National Comprehensive Cancer Network : JNCCN.

[2]  B. Karlan,et al.  Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Richard G. Moore,et al.  Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group trial. , 2013, Gynecologic oncology.

[4]  Rochelle L. Garcia,et al.  BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma , 2013, Cancer.

[5]  I. Kotsopoulos,et al.  Patient groups that fimbriectomy could reduce high grade serous ovarian cancer incidence. , 2013, Gynecologic oncology.

[6]  I. Jacobs,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. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  H. Hollema,et al.  Support of the 'fallopian tube hypothesis' in a prospective series of risk-reducing salpingo-oophorectomy specimens. , 2012, European journal of cancer.

[8]  M. Greene,et al.  New views on the pathogenesis of high-grade pelvic serous carcinoma with suggestions for advancing future research. , 2012, Gynecologic oncology.

[9]  M. Westgren.  Prevention of ovarian cancer – let's do something , 2012, Acta obstetricia et gynecologica Scandinavica.

[10]  J. Simard,et al.  Effectiveness of Risk-Reducing Salpingo-Oophorectomy in Preventing Ovarian Cancer in a High-Risk French Canadian Population , 2012, International Journal of Gynecologic Cancer.

[11]  P. Ouyang,et al.  Bilateral Oophorectomy, Body Mass Index, and Mortality in U.S. Women Aged 40 Years and Older , 2012, Cancer Prevention Research.

[12]  S. Skates.  Ovarian Cancer Screening: Development of the Risk of Ovarian Cancer Algorithm (ROCA) and ROCA Screening Trials , 2012, International Journal of Gynecologic Cancer.

[13]  F. McKeon,et al.  The oviduct and ovarian cancer: causality, clinical implications, and "targeted prevention". , 2012, Clinical obstetrics and gynecology.

[14]  Gord Glendon,et al.  Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer , 2012 .

[15]  A. Berchuck,et al.  Large Prospective Study of Ovarian Cancer Screening in High-Risk Women: CA125 Cut-Point Defined by Menopausal Status , 2011, Cancer Prevention Research.

[16]  L. Dušek,et al.  Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis , 2011, Expert review of anticancer therapy.

[17]  I. Shih,et al.  Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm. , 2011, Human pathology.

[18]  J. Gohagan,et al.  Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. , 2011, JAMA.

[19]  B. Crawford,et al.  Correlation of macroscopic and microscopic pathology in risk reducing salpingo-oophorectomy: implications for intraoperative specimen evaluation. , 2011, Gynecologic oncology.

[20]  D. Oram,et al.  Outcome of risk‐reducing salpingo‐oophorectomy in BRCA carriers and women of unknown mutation status , 2011, BJOG : an international journal of obstetrics and gynaecology.

[21]  J. Peyrat,et al.  Radical fimbriectomy: a reasonable temporary risk-reducing surgery for selected women with a germ line mutation of BRCA 1 or 2 genes? Rationale and preliminary development. , 2011, Gynecologic oncology.

[22]  D. Moore,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 , 2011, International Journal of Gynecologic Cancer.

[23]  S. Mok,et al.  Microscopic and Early-Stage Ovarian Cancers in BRCA1/2 Mutation Carriers: Building a Model for Early BRCA-Associated Tumorigenesis , 2011, Cancer Prevention Research.

[24]  M. D. Post,et al.  Are All Pelvic (Nonuterine) Serous Carcinomas of Tubal Origin , 2011 .

[25]  M. Greene,et al.  Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers? , 2011, American journal of obstetrics and gynecology.

[26]  M. Widschwendter,et al.  Tubal ligation and the risk of ovarian cancer: review and meta-analysis. , 2011, Human reproduction update.

[27]  H. Gevensleben,et al.  Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers , 2011, Archives of Gynecology and Obstetrics.

[28]  T. Conrads,et al.  Novel surgical approaches for sampling the ovarian surface epithelium and proximal fluid proteome. , 2010, Journal of proteome research.

[29]  B. Karlan,et al.  Prevalence of BRCA1 and BRCA2 germ line mutations among women with carcinoma of the fallopian tube. , 2010, Gynecologic oncology.

[30]  Rosalind Eeles,et al.  Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. , 2010, JAMA.

[31]  B. Bonanni,et al.  Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. , 2010, European journal of cancer.

[32]  F. Couch,et al.  Occult ovarian cancers identified at risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers , 2010, Breast Cancer Research and Treatment.

[33]  B. Crawford,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 , 2009, The American journal of surgical pathology.

[34]  O. Gemer,et al.  BRCA Germline Mutations in Women With Uterine Serous Carcinoma-Still a Debate , 2009, International Journal of Gynecologic Cancer.

[35]  M. Nucci,et al.  Coexisting Intraepithelial Serous Carcinomas of the Endometrium and Fallopian Tube: Frequency and Potential Significance , 2009, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[36]  J. Hirst,et al.  High Rates of Occult Fallopian Tube Cancer Diagnosed at Prophylactic Bilateral Salpingo-Oophorectomy , 2009, International Journal of Gynecologic Cancer.

[37]  J. Manson,et al.  Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses’ Health Study , 2009, Obstetrics and gynecology.

[38]  D. Evans,et al.  Risk-reducing surgery for ovarian cancer: outcomes in 300 surgeries suggest a low peritoneal primary risk , 2009, European Journal of Human Genetics.

[39]  Matthew Burnell,et al.  Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) , 2009, Journal of Family Planning and Reproductive Health Care.

[40]  Susan M. Domchek,et al.  Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-oophorectomy in BRCA1 or BRCA2 Mutation Carriers , 2009, Journal of the National Cancer Institute.

[41]  K. Offit,et al.  Breast cancer risks in individuals testing negative for a known family mutation in BRCA1 or BRCA2 , 2009, Breast Cancer Research and Treatment.

[42]  L. Dubeau,et al.  The cell of origin of ovarian epithelial tumours. , 2008, The Lancet. Oncology.

[43]  D. Alberts,et al.  A Prospective Study of Risk-Reducing Salpingo-oophorectomy and Longitudinal CA-125 Screening among Women at Increased Genetic Risk of Ovarian Cancer: Design and Baseline Characteristics: A Gynecologic Oncology Group Study , 2008, Cancer Epidemiology Biomarkers & Prevention.

[44]  V. Beral,et al.  Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23 257 women with ovarian cancer and 87 303 controls , 2008, The Lancet.

[45]  P. Loehrer.  Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation , 2008 .

[46]  N. Mahajan.  Prophylactic salpingo‐oophorectomy in a series of 89 women carrying a BRCA1 or a BRCA2 mutation , 2007, Cancer.

[47]  Ross S Berkowitz,et al.  Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  J. Berkhof,et al.  Serum CA-125 in relation to adnexal dysplasia and cancer in women at hereditary high risk of ovarian cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  Giovanni Parmigiani,et al.  Meta-analysis of BRCA1 and BRCA2 penetrance. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[50]  J. Thigpen.  Clinical and pathologic findings of prophylactic salpingooophorectomies in 159 BRCA1 and BRCA2 carriers , 2007 .

[51]  L. Esserman,et al.  Genetic/familial high-risk assessment , 2010 .

[52]  P. Radice,et al.  Incidental Carcinomas in Prophylactic Specimens in BRCA1 and BRCA2 Germ-line Mutation Carriers, With Emphasis on Fallopian Tube Lesions: Report of 6 Cases and Review of the Literature , 2006, The American journal of surgical pathology.

[53]  Mariza de Andrade,et al.  Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. , 2006, The Lancet. Oncology.

[54]  J. Berkhof,et al.  Low prevalence of (pre) malignant lesions in the breast and high prevalence in the ovary and Fallopian tube in women at hereditary high risk of breast and ovarian cancer , 2006, International journal of cancer.

[55]  F. Couch,et al.  Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. , 2006, JAMA.

[56]  Rochelle L. Garcia,et al.  Predictors of occult neoplasia in women undergoing risk-reducing salpingo-oophorectomy. , 2006, American journal of obstetrics and gynecology.

[57]  Christopher P Crum,et al.  The Tubal Fimbria Is a Preferred Site for Early Adenocarcinoma in Women With Familial Ovarian Cancer Syndrome , 2006, The American journal of surgical pathology.

[58]  P. Neven,et al.  Prophylactic salpingo-oophorectomy in 51 women with familial breast–ovarian cancer: importance of fallopian tube dysplasia , 2005, International Journal of Gynecologic Cancer.

[59]  T. Colgan,et al.  Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers. , 2006, Gynecologic oncology.

[60]  J. Klijn,et al.  Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic women at high risk for ovarian cancer. , 2005, Gynecologic oncology.

[61]  M. Beattie,et al.  Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[62]  M. J. van de Vijver,et al.  Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up , 2004, British Journal of Cancer.

[63]  D. Coppola,et al.  Cytology of human ovarian surface epithelial brushings , 2003, Cancer.

[64]  Rochelle L. Garcia,et al.  Pathologic findings in prophylactic oophorectomy specimens in high-risk women. , 2002, Gynecologic oncology.

[65]  J. Satagopan,et al.  Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. , 2002, The New England journal of medicine.

[66]  Susan L Neuhausen,et al.  Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. , 2002, The New England journal of medicine.

[67]  J. Satagopan,et al.  Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  P. V. van Diest,et al.  Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer , 2001, The Journal of pathology.

[69]  B. Rosen,et al.  Occult Carcinoma in Prophylactic Oophorectomy Specimens: Prevalence and Association With BRCA Germline Mutation Status , 2001, The American journal of surgical pathology.

[70]  J. Niloff,et al.  Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing prophylactic oophorectomy. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[71]  J Gil,et al.  Ovarian dysplasia in prophylactic oophorectomy specimens , 1999, Cancer.

[72]  M. Piver,et al.  Laparoscopic management of women with a family history of ovarian cancer , 1999, Journal of surgical oncology.

[73]  J. Ranstam,et al.  Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  A. Godwin,et al.  Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies. , 1996, Journal of the National Cancer Institute.