Research Article| Volume 162, ISSUE 3, P715-719, September 2021

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Breast cancer incidence in BRCA mutation carriers with ovarian cancer: A longitudal observational study


      • Breast cancer incidence was assessed in ovarian cancer patients carrying BRCA mutations.
      • Breast cancer was diagnosed after ovarian cancer in 6.2% of patients.
      • Overall survival was not statistically different in the patient groups analyzed.
      • Routine breast surveillance may be sufficient in ovarian cancer survivors.



      We evaluated the incidence of breast cancer and overall survival in a multi-center cohort of ovarian cancer patients carrying BRCA1/2 mutations in order to assess risks and formulate optimal preventive interventions and/or surveillance.


      Medical records of 502 BRCA1/2 mutation carriers diagnosed with ovarian cancer between 2000 and 2018 at 7 medical centers in Israel and one in New York were retrospectively analyzed for breast cancer diagnosis. Data included demographics, type of BRCA mutations, surveillance methods, timing of breast cancer diagnosis, and family history of cancer.


      The median age at diagnosis of ovarian cancer was 55.8 years (range, 23.9–90.1). A third (31.5%) had a family history of breast cancer and 17.1% of ovarian cancer. Most patients (67.3%) were Ashkenazi Jews, 72.9% were BRCA1 carriers. Breast cancer preceded ovarian cancer in 17.5% and was diagnosed after ovarian cancer in 6.2%; an additional 2.2% had a synchronous presentation. Median time to breast cancer diagnosis after ovarian cancer was 46.0 months (range, 11–168). Of those diagnosed with both breast cancer and ovarian cancer (n = 31), 83.9% and 16.1% harbored BRCA1 and BRCA2 mutations, respectively. No deaths from breast cancer were recorded. Overall survival did not differ statistically between patients with an ovarian cancer diagnosis only and those diagnosed with breast cancer after ovarian cancer.


      The low incidence of breast cancer after ovarian cancer in women carrying BRCA1/2 mutations suggests that routine breast surveillance, rather than risk-reducing surgical interventions, may be sufficient in ovarian cancer survivors.


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        • Bray F.
        • Ferlay J.
        • Soerjomataram I.
        • Siegel R.L.
        • Torre L.A.
        • Jemal A.
        Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J. Clin. 2018; 68: 394-424
      1. Cancer Stat Facts: Female Breast Cancer. National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER); 2019.

        • Antoniou A.
        • Pharoah P.D.
        • Narod S.
        • Risch H.A.
        • Eyfjord J.E.
        • Hopper J.L.
        • 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
      2. Cancer Stat Facts: Ovarian Cancer. National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER); 2019.

        • Kuchenbaecker K.B.
        • Hopper J.L.
        • Barnes D.R.
        • Phillips K.A.
        • Mooij T.M.
        • Roos-Blom M.J.
        • et al.
        Risks of breast, ovarian, and contralateral breast Cancer for BRCA1 and BRCA2 mutation carriers.
        JAMA : the journal of the American Medical Association. 2017; 317: 2402-2416
        • Kotsopoulos J.
        • Gronwald J.
        • Karlan B.
        • Rosen B.
        • Huzarski T.
        • Moller P.
        • et al.
        Age-specific ovarian cancer risks among women with a BRCA1 or BRCA2 mutation.
        Gynecol. Oncol. 2018; 150: 85-91
        • Hirsh-Yechezkel G.
        • Chetrit A.
        • Lubin F.
        • Friedman E.
        • Peretz T.
        • Gershoni R.
        • et al.
        Population attributes affecting the prevalence of BRCA mutation carriers in epithelial ovarian cancer cases in Israel.
        Gynecol. Oncol. 2003; 89: 494-498
        • Montemorano L.
        • Lightfoot M.D.
        • Bixel K.
        Role of Olaparib as maintenance treatment for ovarian Cancer: the evidence to date.
        Onco Targets Ther. 2019; 12: 11497-11506
        • Meijers-Heijboer H.
        • van Geel B.
        • van Putten W.L.
        • Henzen-Logmans S.C.
        • Seynaeve C.
        • Menke-Pluymers M.B.
        • et al.
        Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation.
        N. Engl. J. Med. 2001; 345: 159-164
      3. T.R. Rebbeck, T. Friebel, H.T. Lynch, S.L. Neuhausen, L. van 't Veer, J.E. Garber, et al., Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 22 (2004) 1055–1062.

        • Ludwig K.K.
        • Neuner J.
        • Butler A.
        • Geurts J.L.
        • Kong A.L.
        Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review.
        Am. J. Surg. 2016; 212: 660-669
        • Domchek S.M.
        • Friebel T.M.
        • Singer C.F.
        • Evans D.G.
        • Lynch H.T.
        • Isaacs C.
        • et al.
        Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
        JAMA : the journal of the American Medical Association. 2010; 304: 967-975
      4. K.E. Lewis, K.H. Lu, A.M. Klimczak, S.C. Mok, Recommendations and Choices for BRCA Mutation Carriers at Risk for Ovarian Cancer: A Complicated Decision. Cancers (Basel). 10 (2018).

        • Terry M.B.
        • Daly M.B.
        • Phillips K.A.
        • Ma X.
        • Zeinomar N.
        • Leoce N.
        • et al.
        Risk-reducing oophorectomy and breast Cancer risk across the Spectrum of familial risk.
        J. Natl. Cancer Inst. 2019; 111: 331-334
      5. B.A. Heemskerk-Gerritsen, C. Seynaeve, C.J. van Asperen, M.G. Ausems, J.M. Collee, H.C. van Doorn, et al., Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst. 107 (2015).

      6. J. Kotsopoulos, T. Huzarski, J. Gronwald, C.F. Singer, P. Moller, H.T. Lynch, et al., Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. J Natl Cancer Inst. 109 (2017).

        • Padamsee T.J.
        • Wills C.E.
        • Yee L.D.
        • Paskett E.D.
        Decision making for breast cancer prevention among women at elevated risk.
        Breast Cancer Res. 2017; 19: 34
        • Domchek S.M.
        • Jhaveri K.
        • Patil S.
        • Stopfer J.E.
        • Hudis C.
        • Powers J.
        • et al.
        Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer.
        Cancer. 2013; 119: 1344-1348
        • Vencken P.M.
        • Kriege M.
        • Hooning M.
        • Menke-Pluymers M.B.
        • Heemskerk-Gerritsen B.A.
        • van Doorn L.C.
        • et al.
        The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers: implications for counseling.
        Cancer. 2013; 119: 955-962
        • Gangi A.
        • Cass I.
        • Paik D.
        • Barmparas G.
        • Karlan B.
        • Dang C.
        • et al.
        Breast cancer following ovarian cancer in BRCA mutation carriers.
        JAMA Surg. 2014; 149: 1306-1313
        • McGee J.
        • Giannakeas V.
        • Karlan B.
        • Lubinski J.
        • Gronwald J.
        • Rosen B.
        • et al.
        Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: is preventive mastectomy warranted?.
        Gynecol. Oncol. 2017; 145: 346-351
        • Warner E.
        • Hill K.
        • Causer P.
        • Plewes D.
        • Jong R.
        • Yaffe M.
        • et al.
        Prospective study of breast cancer incidence in women with a BRCA1 or BRCA2 mutation under surveillance with and without magnetic resonance imaging.
        J. Clin. Oncol. 2011; 29: 1664-1669
      7. NCCN. Genetic/familial high risk assessment: breast and ovarian. Version 2.2017. . NCCN Clinical Practice Guidelines in Oncology. Fort Washington (PA): National Comprehensive Cancer Network; 2016.

        • Bernstein-Molho R.
        • Kaufman B.
        • Ben David M.A.
        • Sklair-Levy M.
        • Feldman D.M.
        • Zippel D.
        • et al.
        Breast cancer surveillance for BRCA1/2 mutation carriers - is "early detection" early enough?.
        Breast. 2020; 49: 81-86
        • Fong A.
        • Cass I.
        • John C.
        • Gillen J.
        • Moore K.M.
        • Gangi A.
        • et al.
        Breast Cancer surveillance following ovarian Cancer in BRCA mutation carriers.
        Am. Surg. 2020; 86: 1243-1247
        • Poveda A.
        • Floquet A.
        • Ledermann J.A.
        • Asher R.
        • Penson R.T.
        • Oza A.M.
        • et al.
        SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial.
        Lancet Oncol. 2021; 22: 620-631