title: Long term follow up of BRCA1 and BRCA2 mutation carriers with unsuspected neoplasia identified at risk reducing salpingo-oophorectomy.
abstract: OBJECTIVE
  The reported incidence of neoplasia identified at the time of risk-reducing salpingo-oophorectomy (RRSO) in germline BRCA1/2 mutation carriers ranges from 4 to 12% but long-term outcomes have not been described. We evaluated recurrence and survival outcomes of mutation carriers with neoplastic lesions identified at RRSO.
  
  
  METHODS
  We identified BRCA1/2 mutation carriers with neoplasia at RRSO at three institutions. Data was collected on clinical variables, adjuvant treatment and follow-up.
  
  
  RESULTS
  We identified 32 mutation carriers with invasive carcinomas (n=15) or high-grade intraepithelial neoplasia (n=17) that were not suspected prior to surgery. 26 occurred in BRCA1 and 6 in BRCA2 mutation carriers. Median and mean age for carcinomas were 50 years and 49.3 respectively, significantly younger than for intraepithelial neoplasm, median 53 years, and mean 55 years (p=0.04). For the 15 invasive carcinomas, median follow up was 88 months (range 45-172 months), 7 recurred (47%), median time to recurrence was 32.5 months and 3 have died of disease; 1 additional patient died of breast cancer. Overall survival was 73%, disease specific overall survival was 80% and disease free survival was 66%. For the 17 high-grade intraepithelial neoplasms, median follow up was 80 months (range 40-150), 4 were treated with chemotherapy. One recurred at 43 months and is currently not on therapy with a normal CA125, 16 months later. All patients with noninvasive neoplasia are alive.
  
  
  CONCLUSIONS
  BRCA1 and BRCA2 mutation carriers with unsuspected invasive carcinoma at RRSO have a relatively high rate of recurrence despite predominantly early stage, small volume disease. High-grade intraepithelial neoplasms rarely recur as carcinoma and may not require adjuvant chemotherapy.
authors: Cancer Risk Program, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Bethan.Powell@kp.org
authors: C B
authors: CB
authors: Powell
authors: E M
authors: EM
authors: Swisher
authors: I
authors: I
authors: Cass
authors: J
authors: J
authors: McLennan
authors: B
authors: B
authors: Norquist
authors: R L
authors: RL
authors: Garcia
authors: J
authors: J
authors: Lester
authors: B Y
authors: BY
authors: Karlan
authors: L
authors: L
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005185:Fallopian Tube Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D010052:Ovariectomy; D058994:Salpingectomy; D016019:Survival Analysis; D016896:Treatment Outcome
references: Am J Surg Pathol. 2006 Oct;30(10):1222-30
references: 17001151
references: Am J Surg Pathol. 2002 Feb;26(2):171-8
references: 11812938
references: Am J Surg Pathol. 2007 Feb;31(2):161-9
references: 17255760
references: Gynecol Oncol. 2002 Oct;87(1):52-6
references: 12468342
references: J Clin Oncol. 2008 Sep 1;26(25):4160-5
references: 18757330
references: Gynecol Oncol. 2005 Feb;96(2):439-43
references: 15661233
references: J Clin Oncol. 2005 Oct 20;23(30):7491-6
references: 16234515
references: Int J Gynecol Pathol. 2004 Jan;23(1):35-40
references: 14668548
references: BJOG. 2011 Jun;118(7):814-24
references: 21392246
references: J Clin Oncol. 2005 Nov 1;23(31):7804-10
references: 16219936
references: Adv Anat Pathol. 2006 Jan;13(1):1-7
references: 16462151
references: Gynecol Oncol. 2002 Jun;85(3):397-403
references: 12051865
references: Am J Obstet Gynecol. 2011 Jan;204(1):19.e1-6
references: 20619389
references: Gynecol Oncol. 2012 Jun;125(3):683-6
references: 22425664
references: JAMA. 2006 Jul 12;296(2):185-92
references: 16835424
references: Gynecol Oncol. 2006 Jan;100(1):58-64
references: 16137750
references: Int J Gynecol Cancer. 2009 Jan;19(1):58-64
references: 19258943
references: Am J Obstet Gynecol. 2006 Jun;194(6):1702-9
references: 16731090
references: Gynecol Oncol. 2012 Feb;124(2):185-91
references: 22019526
references: Diagn Histopathol (Oxf). 2008 Aug;14(8):352-365
references: 20953242
references: Am J Surg Pathol. 2006 Feb;30(2):230-6
references: 16434898
references: J Clin Oncol. 2008 Nov 10;26(32):5284-93
references: 18854563
references: Br J Cancer. 2004 Apr 19;90(8):1492-7
references: 15083174
references: Clin Med Res. 2007 Mar;5(1):35-44
references: 17456833
references: Am J Surg Pathol. 2010 Mar;34(3):433-43
references: 20154587
references: JAMA. 2010 Sep 1;304(9):967-75
references: 20810374
references: J Clin Oncol. 2005 Jan 1;23(1):127-32
references: 15625367
references: J Natl Cancer Inst. 2009 Jan 21;101(2):80-7
references: 19141781
references: Int J Gynecol Cancer. 2012 May;22 Suppl 1:S1
references: 22543910
references: J Clin Oncol. 2008 Jan 1;26(1):20-5
references: 18165636
references: Eur J Cancer. 2013 Jan;49(1):132-41
references: 22921157
references: Am J Surg Pathol. 2009 Dec;33(12):1878-85
references: 19898224
references: Am J Surg Pathol. 2004 Aug;28(8):1112-4
references: 15252324
references: Curr Opin Obstet Gynecol. 2007 Feb;19(1):27-30
references: 17218848
references: J Clin Oncol. 2007 Sep 1;25(25):3985-90
references: 17761984
references: J Natl Cancer Inst. 1999 Apr 7;91(7):626-8
references: 10203282
references: Cancer. 1999 Oct 15;86(8):1544-50
references: 10526284
references: J Pathol. 2007 Jan;211(1):26-35
references: 17117391
references: Gynecol Oncol. 2001 Feb;80(2):176-80
references: 11161856
references: Int J Gynecol Cancer. 2011 Jul;21(5):846-51
references: 21670699