The Challenge of Evaluating Adnexal Masses in Patients With Breast Cancer

Published:March 12, 2018DOI:


      This narrative literature review addresses the problem of an adnexal mass discovered during the course of breast cancer (BC) care, which may represent a benign condition, a metastatic process, or a primary ovarian cancer (OC), clinical scenarios associated with distinct physiopathology and prognosis. Furthermore, the coexistence of BC and OC in the same patient may be owing to a hereditary disorder, deserving specific management strategies and counseling. The initial detection and evaluation of an adnexal mass in a patient with BC requires a high index of suspicion, and the initial workup should include a thorough medical history and physical examination, measurement of tumor markers, complete blood count, and imaging tests. Transvaginal ultrasonography remains the standard tool, and findings suggestive of malignancy include bilateral tumors, thick septations, predominance of a solid component, Doppler flow to the solid component, and ascites. From the pathology point of view, features that are suggestive of metastatic disease include bilaterality, mild ovarian enlargement, vascular emboli, no omental deposits, and the absence of transition from benign to malignant epithelium. Although there is a considerable overlap in OC and BC immunohistochemical profiles, BC usually stain positive for GCDFP-15 and negative for vimentine, PAX8, and WT1, and OC often stain positive for CK7, PAX8, WT1, and to mesothelin. Genetic counselling should always be indicated in this clinical scenario. In conclusion, diagnostic spectrum of an ovarian mass in a patient with BC is broad, and a systematic multi-professional strategy is necessary to conduct these challenging cases.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Breast Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer.
        (Available at:) (Accessed: January 5, 2018)
        • Reid B.
        • Permuth J.
        • Sellers T.
        Epidemiology of ovarian cancer: a review.
        Cancer Biol Med. 2017; 14: 9-32
      2. National Institutes of Health Consensus Development Conference Statement. Ovarian cancer: screening, treatment, and follow-up.
        Gynecol Oncol. 1994; 55: S4-14
        • Cardoso F.
        • Costa A.
        • Senkus E.
        • et al.
        3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3).
        Ann Oncol. 2016; 0: 1-17
        • Simpikins F.
        • Zahurak M.
        • Armstrong D.
        • Grumbine F.
        • Bristow R.
        Ovarian malignancy in breast cancer patients with an adnexal mass.
        Obstet Gynecol. 2005; 105: 507-513
        • Curtin J.P.
        • Barakat R.R.
        • Hoskins W.J.
        Ovarian disease in women with breast cancer.
        Obstet Gynecol. 1994; 84: 449-452
        • Yamanishi Y.
        • Koshiyama M.
        • Ohnaka M.
        • et al.
        Pathways of metastases from primary organs to the ovaries.
        Obstet Gynecol Int. 2011; 2011: 612817
        • Perrotin F.
        • Marret H.
        • Bouquin R.
        • Fischer-Perrotin N.
        • Lansac J.
        • Body G.
        [Incidence, diagnosis and prognosis of ovarian metastasis in breast cancer].
        Gynecol Obstet Fertil. 2001; 29: 308-315
        • Lee S.J.
        • Bae J.H.
        • Lee A.W.
        • Tong S.Y.
        • Park Y.G.
        • Park J.S.
        Clinical characteristics of metastastic tumors to the ovaries.
        J Korean Med Sci. 2009; 24: 114-119
        • Ayhan A.
        • Guvenal T.
        • Salman M.C.
        • Ozyuncu O.
        • Sakinci M.
        • Basaran M.
        The role of cytoreductive surgery in nongenital cancer metastatic to the ovaries.
        Gynecol Oncol. 2005; 98: 235-241
        • Antila R.
        • Jalkanen J.
        • Heikinheimo O.
        Comparison of secondary and primary ovarian malignancies reveals differences in their pre and perioperative characteristics.
        Gynecol Oncol. 2006; 101: 97-101
        • Dubois N.
        • Willems T.
        • Myant N.
        [Ovarian metastasis of breast cancer: a case report. Role of cytoreductive surgery].
        J Gynecol Obstete Biol Reprod (Paris). 2009; 38: 242-245
        • Skirnisdottir I.
        • Garmo H.
        • Holmberg L.
        Non-genital tract metastasis to the ovaries presented as ovarian tumors in Sweden: occurrence, origin and survival compared to ovarian cancer.
        Gynecol Oncol. 2007; 105: 166-171
        • Tserkezoglou A.
        • Kontou S.
        • Hadjieleftheriou G.
        • et al.
        Primary and metastatic ovarian cancer in patients with prior breast carcinoma. Pre-operative markers and treatment results.
        Anticancer Res. 2006; 26: 2339-2344
        • Bigorie V.
        • Morice P.
        • Duvillard P.
        • et al.
        Ovarian metastasis from breast cancer.
        Cancer. 2010; 116: 799-804
        • Eitan R.
        • Gemignani M.L.
        • Venkatraman E.S.
        • Barakat R.R.
        • Abu-Rustum N.R.
        Breast cancer metastatic to the abdomen and pelvis: role of surgical resection.
        Gynecol Oncol. 2003; 90: 397-401
        • Le Thai N.
        • Lasry S.
        • Brunet M.
        • Harvey P.
        • Rouesse J.
        Cancer of the ovary after cancer of the breast. 45 cases.
        Gynecol Obstet Biol Reprod (Paris). 1991; 20: 1043-1048
        • Guerriero S.
        • Alcazar J.L.
        • Pascual M.A.
        • Ajossa S.
        • Olartecoechea B.
        • Hereter L.
        Preoperative diagnosis of metastatic ovarian cancer is related to origin of primary tumor.
        Ultrasound Obstet Gynecol. 2012; 39: 581-586
        • Brown D.L.
        • Zhou K.H.
        • Tempany C.M.
        • et al.
        Primary versus secondary ovarian malignancy: imaging findings of adnexal mass in the Radiology Diagnostic Oncology Group Study.
        Radiology. 2001; 219: 213-218
        • Ueland F.R.
        • DePriest P.D.
        • Pavlik E.J.
        • Kryscio R.J.
        • van Nagell Jr., J.R.
        Preoperative differentiation of malignant from benign ovarian tumors: the efficacy of morphology indexing and doppler flow sonography.
        Gynecol Oncol. 2003; 91: 46-50
        • Abd El hafez A.
        • Monir A.
        Diagnostic spectrum of ovarian masses in women with breast cancer; magnetic resonance imaging: histopathology correlation.
        Ann Diagn Pathol. 2013; 17: 441-447
        • Quan M.L.
        • Fey J.
        • Eitan R.
        • et al.
        Role of laparoscopy in the evaluation of the adnexa in patients with stage IV breast cancer.
        Gynecol Oncol. 2004; 92: 327-330
        • Abu-Rustum N.R.
        • Aghajanian C.A.
        • Venkatraman E.S.
        • Feroz F.
        • Barakat R.R.
        Metastatic breast carcinoma to the abdomen and pelvis.
        Gynecol Oncol. 1997; 66: 41-44
        • Reinert T.
        • Barrios C.H.
        Optimal management of hormone receptor positive metastatic breast cancer in 2016.
        Ther Adv Med Oncol. 2015; 7: 304-320
        • Rugo H.S.
        • Rumble R.B.
        • Macrae E.
        • et al.
        Endocrine therapy for hormone receptor–positive metastatic breast cancer: American Society of Clinical Oncology Guideline.
        J Clin Oncol. 2016; 34: 3069-3103
        • Jelovac D.
        • Armstrong D.K.
        Recent progress in the diagnosis and treatment of ovarian cancer.
        CA Cancer J Clin. 2011; 61: 183-203
        • Hann L.E.
        • Lui D.M.
        • Shi W.
        • Bach A.M.
        • Selland D.L.
        • Castiel M.
        Adnexal masses in women with breast cancer: US findings with clinical and histopathologic correlation.
        Radiology. 2000; 216: 242-247
        • Olawaiye A.
        • Caesar L.
        • Walsh D.
        • et al.
        Analysis of the time interval between diagnoses in women with double primary breast and ovarian or primary peritoneal cancers.
        Gynecol Oncol. 2004; 94: 796-802
        • Suris-Swartz P.J.
        • Sschildkraut J.M.
        • Vine M.F.
        • Hertz-Picciotto I.
        Age at diagnosis and multiple primary cancers of the breast and ovary.
        Breast Cancer Res Treat. 1996; 41: 21-29
        • Zanetta G.
        • Rota S.
        • Chiari S.
        • et al.
        The accuracy of staging: and important prognostic determinator in stage I ovarian carcinoma.
        Ann Oncol. 1998; 9: 1097-1101
        • Abeliovich D.
        • Kaduri L.
        • Lerer I.
        • et al.
        The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women.
        Am J Hum Genet. 1997; 60: 505-514
        • Fishman A.
        • Dekel E.
        • Chetrit A.
        • et al.
        Patients with double primary tumors in the breast and ovary- clinical characteristics and BRCA1-2 mutations status.
        Gynecol Oncol. 2000; 79: 74-78
        • Bergfeldt K.
        • Rydh B.
        • Granath F.
        • et al.
        Risk of ovarian cancer in breast-cancer patients with a family history of breast or ovarian cancer: a population-based cohort study.
        Lancet. 2002; 360: 891-894
        • Ledermann J.A.
        • Raja F.A.
        • Fotopoulou C.
        • Gonzalez-Martin A.
        • Colombo N.
        • Sessa C.
        • ESMO Guidelines Working Group
        Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2013; 24: vi24-vi32
        • Burger R.
        • Brady M.
        • Bookman M.
        • et al.
        • Gynecologic Oncology Group
        Incorporation of bevacizumab in the primary treatment of ovarian cancer.
        N Engl J Med. 2011; 365: 2473-2483
        • De Picciotto N.
        • Cacheux W.
        • Roth A.
        • Chappuis P.O.
        • Labidi-Galy S.I.
        Ovarian cancer: status of homologous recombination pathway as a predictor of drug response.
        Crit Rev Oncol Hematol. 2016; 101: 50-59
        • Quinn J.E.
        • Carser J.E.
        • James C.R.
        • Kennedy R.D.
        • Harkin D.P.
        BRCA1 and implications for response to chemotherapy in ovarian cancer.
        Gynecol Oncol. 2009; 113: 134-142
        • Ledermann J.
        • Harter P.
        • Gourley C.
        • et al.
        Olaparib maintanance in platinum-sensitive relapsed ovarian cancer.
        N Engl J Med. 2012; 366: 1382-1392
        • Stratton J.F.
        • Gayther S.S.
        • Russell P.
        • et al.
        Contribution of BRCA1 mutations to ovarian cancer.
        N Engl J Med. 1997; 336: 1125-1130
        • Smith S.A.
        • Richards W.E.
        • Caito K.
        • et al.
        BRCA1 germline mutations and polymorphisms in a clinic-based series of ovarian cancer cases: a Gynecologic Oncology Group study.
        Gynecol Oncol. 2001; 83: 586-592
        • Ledermann J.A.
        • Drew Y.
        • Kristeleit R.S.
        Homologous recombination deficiency and ovarian cancer.
        Eur J Cancer. 2016; 60: 49-58
        • Pan Z.
        • Xie X.
        BRCA mutations in the manifestation and treatment of ovarian cancer.
        Oncotarget. 2017; 8: 97657-97670
        • George A.
        • Kaye S.
        • Banerjee S.
        Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer.
        Nat Rev Clin Oncol. 2017; 14: 284-296
        • Evans T.
        • Matulonis U.
        PARP inhibitors in ovarian cancer: evidence, experience and clinical potential.
        Ther Adv Med Oncol. 2017; 9: 253-267
        • Walsh T.
        • Casadei S.
        • Lee M.K.
        • et al.
        Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.
        Proc Natl Acad Sci U S A. 2011; 108: 18032-18037
        • Norquist B.M.
        • Harrel M.I.
        • Brady M.F.
        • et al.
        Inherited mutations in women with ovarian carcinoma.
        JAMA Oncol. 2016; 2: 482-490
        • Toss A.
        • Tomasello C.
        • Razzaboni E.
        • et al.
        Hereditary ovarian cancer: not only BRCA 1 and 2 genes.
        Biomed Res Int. 2015; 2015: 341723
        • Givens V.
        • Mitchell G.E.
        • Harraway-Smith C.
        • Reddy A.
        • Maness D.L.
        Diagnosis and management of adnexal masses.
        Am Fam Physician. 2009; 80: 815-820
        • Chen V.W.
        • Ruiz B.
        • Killeen J.L.
        • Coté T.R.
        • Wu X.C.
        • Correa C.N.
        Pathology and classification of ovarian tumors.
        Cancer. 2003; 97: 2631-2642
        • American College of Obstetricians and Gynecologists
        Management of adnexal masses.
        American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin, No 83, Washington (DC)2007
        • Bottoni P.
        • Scatena R.
        The role of CA 125 as tumor marker: biochemical and clinical aspects.
        Adv Exp Med Biol. 2015; 867: 229-244
        • Johnson C.C.
        • Kessel B.
        • Riley T.L.
        • et al.
        • Prostate, Lung, Colorectal and Ovarian Cancer Project Team
        The epidemiology of CA-125 in women without evidence of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial.
        Gynecol Oncol. 2008; 110: 383-389
        • Fu Y.
        • Li H.
        Assessing clinical significance of serum CA15-3 and carcinoembryonic antigen (CEA) levels in breast cancer patients: a meta-analysis.
        Med Sci Monit. 2016; 22: 3154-3162
        • Geng B.
        • Liang M.M.
        • Ye X.B.
        • Zhao W.Y.
        Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.
        Mol Clin Oncol. 2015; 3: 232-236
        • Sagi-Dain L.
        • Lavie O.
        • Auslander R.
        • Sagi S.
        Clinical use and optimal cutoff value of CA15-3 in evaluation of adnexal mass: retrospective cohort study and review of the literature.
        Am J Clin Oncol. 2017; ([Epub ahead of print])
        • Bristow R.E.
        • Smith A.
        • Zhang Z.
        • et al.
        Ovarian malignancy risk stratification of the adnexal mass using a multivariate index assay.
        Gynecol Oncol. 2013; 128: 252-259
        • Moore R.G.
        • Miller M.C.
        • DiSilvestro P.
        • et al.
        Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass.
        Obstet Gynecol. 2011; 118: 280-288
        • Patel M.
        Practical approach to the adnexal mass.
        Radiol Clin North Am. 2006; 44: 879-899
        • Timmerman D.
        • Testa A.C.
        • Bourne T.
        • et al.
        Simple ultrasound-based rules for the diagnosis of ovarian cancer.
        Ultrasound Obstet Gynecol. 2008; 31: 681-690
        • Imaoka I.
        • Wada A.
        • Kajy Y.
        • et al.
        Developing an MR imaging strategy for diagnosis of ovarian masses.
        Radiographics. 2006; 26: 1431-1448
        • Powary M.
        • Dey P.
        • Gupta S.K.
        • Saha S.
        Metastatic tumors of the ovary: a clinico-pathological study.
        Indian J Pathol Microbiol. 2003; 46: 412-415
        • Le Bouëdec G.
        • de Latour M.
        • Levrel O.
        • Dauplat J.
        [Krükenberg tumors of breast origin. 10 cases].
        Presse Med. 1997; 26: 454-457
        • Al-Agha O.M.
        • Nicastri A.D.
        An in-depth look at Krukenberg tumor: an overview.
        Arch Pathol Lab Med. 2007; 130: 1725-1730
        • Kyokawa T.
        • Young R.H.
        • Scully R.E.
        Krukenberg tumors of the ovary: a clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations.
        Am J Surg Pathol. 2006; 30: 277-299
        • Tornos C.
        • Solslow R.
        • Chen S.
        • et al.
        Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary.
        Am J Surg Pathol. 2005; 29: 1482-1489
        • Nonaka D.
        • Chiriboga L.
        • Soslow R.A.
        Expression of PAX8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas.
        Am J Surg Pathol. 2008; 32: 1566-1571
        • Wick M.R.
        • Lillemoe T.J.
        • Copland G.T.
        • Swanson P.E.
        • Manivel J.C.
        • Kiang D.T.
        Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin.
        Hum Pathol. 1989; 20: 281-287
        • Raab S.S.
        • Berg L.C.
        • Swanson P.E.
        • Wick M.R.
        Adenocarcinoma in the lung in patients with breast cancer: a prospective analysis of the discriminatory value of immunohistology.
        Am J Clin Pathol. 1993; 100: 27-35
        • Monteagudo C.
        • Merino M.J.
        • LaPorte N.
        • Neumann R.D.
        Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary.
        Hum Pathol. 1991; 22: 368-372
        • Espinosa I.
        • Gallardo A.
        • D’Angelo E.
        • Mozos A.
        • Lerma E.
        • Prat J.
        Simultaneous carcinomas of the breast and ovary: utility of Pax-8, WT-1, and GATA3 for distinguishing independent primary tumors from metastases.
        Int J Gynecol Pathol. 2015; 34: 257-265
        • Kandalaft P.L.
        • Gown A.M.
        Practical applications of immunohistochemistry: carcinomas of unkown primary site.
        Arch Pathol Lab Med. 2016; 140: 508-523
        • Cimino-Mathews A.
        • Subhawong A.P.
        • Illei P.B.
        • et al.
        GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas.
        Hum Pathol. 2013; 44: 1341-1349
        • Ordóñez N.G.
        Application of mesothelin staining in tumor diagnosis.
        Am J Surg Pathol. 2003; 27: 1418-1428
        • Lotan T.L.
        • Ye H.
        • Melamed J.
        • Wu X.R.
        • IeM Shih
        • Epstein J.I.
        Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma.
        Am J Surg Pathol. 2009; 33: 1037-1041