Breast Cancer Following Ovarian Cancer in BRCA Mutation Carriers | Breast Cancer | JAMA Surgery | JAMA Network
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 National Institutes of Health. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER). Accessed February 2, 2013.
Antoniou  A, Pharoah  PD, 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(5):1117-1130.PubMedGoogle ScholarCrossref
Anglian Breast Cancer Study Group.  Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases.  Br J Cancer. 2000;83(10):1301-1308.PubMedGoogle ScholarCrossref
Easton  DF, Ford  D, Bishop  DT; Breast Cancer Linkage Consortium.  Breast and ovarian cancer incidence in BRCA1-mutation carriers.  Am J Hum Genet. 1995;56(1):265-271.PubMedGoogle Scholar
Ford  D, Easton  DF, Stratton  M,  et al; Breast Cancer Linkage Consortium.  Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families.  Am J Hum Genet. 1998;62(3):676-689.PubMedGoogle ScholarCrossref
Martin  AM, Blackwood  MA, Antin-Ozerkis  D,  et al.  Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast cancer risk evaluation clinic.  J Clin Oncol. 2001;19(8):2247-2253.PubMedGoogle Scholar
Santarosa  M, Dolcetti  R, Magri  MD,  et al.  BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy.  Int J Cancer. 1999;83(1):5-9.PubMedGoogle ScholarCrossref
Olopade  OI, Artioli  G.  Efficacy of risk-reducing salpingo-oophorectomy in women with BRCA-1 and BRCA-2 mutations.  Breast J. 2004;10(suppl 1):S5-S9.PubMedGoogle ScholarCrossref
Rebbeck  TR, Lynch  HT, Neuhausen  SL,  et al; Prevention and Observation of Surgical End Points Study Group.  Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.  N Engl J Med. 2002;346(21):1616-1622.PubMedGoogle ScholarCrossref
Kauff  ND, Domchek  SM, Friebel  TM,  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(8):1331-1337.PubMedGoogle ScholarCrossref
van der Kolk  DM, de Bock  GH, Leegte  BK,  et al.  Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age.  Breast Cancer Res Treat. 2010;124(3):643-651.PubMedGoogle ScholarCrossref
Fisher  B, Costantino  JP, Wickerham  DL,  et al.  Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.  J Natl Cancer Inst. 1998;90(18):1371-1388.PubMedGoogle ScholarCrossref
Vogel  VG, Costantino  JP, Wickerham  DL,  et al; National Surgical Adjuvant Breast and Bowel Project (NSABP).  Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial.  JAMA. 2006;295(23):2727-2741.PubMedGoogle ScholarCrossref
Graeser  MK, Engel  C, Rhiem  K,  et al.  Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers.  J Clin Oncol. 2009;27(35):5887-5892.PubMedGoogle ScholarCrossref
Eerola  H, Pukkala  E, Pyrhönen  S, Blomqvist  C, Sankila  R, Nevanlinna  H.  Risk of cancer in BRCA1 and BRCA2 mutation-positive and -negative breast cancer families (Finland).  Cancer Causes Control. 2001;12(8):739-746.PubMedGoogle ScholarCrossref
Chen  S, Parmigiani  G.  Meta-analysis of BRCA1 and BRCA2 penetrance.  J Clin Oncol. 2007;25(11):1329-1333.PubMedGoogle ScholarCrossref
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(9):967-975.PubMedGoogle ScholarCrossref
Eisen  A, Lubinski  J, Klijn  J,  et al.  Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study.  J Clin Oncol. 2005;23(30):7491-7496.PubMedGoogle ScholarCrossref
Domchek  SM, Jhaveri  K, Patil  S,  et al.  Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer.  Cancer. 2013;119(7):1344-1348.PubMedGoogle ScholarCrossref
Quinn  JE, Carser  JE, James  CR, Kennedy  RD, Harkin  DP.  BRCA1 and implications for response to chemotherapy in ovarian cancer.  Gynecol Oncol. 2009;113(1):134-142.PubMedGoogle ScholarCrossref
Vencken  PM, Kriege  M, Hoogwerf  D,  et al.  Chemosensitivity and outcome of BRCA1- and BRCA2-associated ovarian cancer patients after first-line chemotherapy compared with sporadic ovarian cancer patients.  Ann Oncol. 2011;22(6):1346-1352.PubMedGoogle ScholarCrossref
Reding  KW, Bernstein  JL, Langholz  BM,  et al; WECARE Collaborative Study Group.  Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer.  Breast Cancer Res Treat. 2010;123(2):491-498.PubMedGoogle ScholarCrossref
Kriege  M, Brekelmans  CT, Boetes  C,  et al; Magnetic Resonance Imaging Screening Study Group.  Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.  N Engl J Med. 2004;351(5):427-437.PubMedGoogle ScholarCrossref
Leach  MO, Boggis  CR, Dixon  AK,  et al; MARIBS study group.  Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS).  Lancet. 2005;365(9473):1769-1778.PubMedGoogle ScholarCrossref
Boyd  J, Sonoda  Y, Federici  MG,  et al.  Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.  JAMA. 2000;283(17):2260-2265.PubMedGoogle ScholarCrossref
Struewing  JP, Hartge  P, Wacholder  S,  et al.  The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.  N Engl J Med. 1997;336(20):1401-1408.PubMedGoogle ScholarCrossref
Original Investigation
Pacific Coast Surgical Association
December 2014

Breast Cancer Following Ovarian Cancer in BRCA Mutation Carriers

Author Affiliations
  • 1Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
  • 2Division of Gynecology-Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California
JAMA Surg. 2014;149(12):1306-1313. doi:10.1001/jamasurg.2014.1081

Importance  BRCA mutation carriers are at increased risk of developing breast cancer. However, the incidence of breast cancer after a diagnosis of epithelial ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred to as pelvic serous carcinomas, is not well known. Optimal breast cancer surveillance and detection for these patients have also not been well characterized.

Objectives  To determine the incidence of breast cancer after a diagnosis of EOC and to evaluate the need for breast cancer surveillance for these patients.

Design, Setting, and Participants  A retrospective database review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV) between 1998 and 2012 at an academic medical center with gynecologic and breast cancer centers.

Main Outcomes and Measures  Incidence of breast cancer and methods of surveillance.

Results  Of 364 patients, 135 (37.1%) were found to carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%) developed breast cancer. The median time from diagnosis of EOC to diagnosis of breast cancer was 50.5 months. Annual mammography was performed for 80 patients (59.3%), with annual magnetic resonance imaging of the breasts performed for 60 patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3 (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast cancer detected during a prophylactic mastectomy. Seven patients with breast cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage breast cancer (stages 0-II). Four patients (33.3%) received adjuvant chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%) died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year survival rate for the entire cohort of 135 patients was 17.0%.

Conclusions and Relevance  The risk of metachronous breast cancer is low in patients with known BRCA mutations and EOC. A majority of these cases of breast cancer at an early stage are detected by use of mammography. Despite the small number of patients in our study, these results suggest that optimal breast cancer surveillance for patients with BRCA-associated EOC needs to be reevaluated given the low incidence of breast cancer among these high-risk patients. Confirmation of our findings from larger studies seems to be indicated.