Axillary nodal metastases from carcinoma of unknown primary (CUPAx): a systematic review of published evidence

  • George Pentheroudakis
  • George Lazaridis
  • Nicholas Pavlidis


Axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary (CUPAx) represent a rare clinical entity without consensus on its biology, management and outcome. We systematically reviewed published CUPAx series and identified 24 retrospective studies enrolling 689 patients from 1975 till 2006. CUPAx affected women at a mean age of 52 years, 66% of whom post-menopausal harbouring low-volume (N1, 48%) or high-volume (52%) nodal disease from ductal adenocarcinoma (83%). Among a total of 446 patients managed with mastectomy, a small breast primary was identified histologically in 321 (72% of cases). Hormone receptor protein expression was observed in 40–50% of cases, while HER2 overexpression in 31%. CUPAx patients were managed with axillary lymph node dissection coupled to mastectomy (59%), primary breast irradiation (26%) or observation (15%). Observation was associated with high locoregional relapse rates (42%) and risk of metastatic spread. Mastectomy or radiotherapy provided locoregional disease control in 75–85% of cases, while adjuvant systemic therapy was associated with a non-significant trend for improved survival in few series. Five-year survival ranged from 59.4 to 88% at a median follow-up of 62 months (mean 5-year survival 72%), with axillary tumour burden being the pivotal prognostic factor. CUPAx is associated with similar presentation, biology and outcome to resected node-positive overt breast cancer and should be treated accordingly.


Axillary metastases Cancer of unknown primary Prognosis 


Conflict of interest statement

The authors declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within that could inappropriately influence (bias) their work.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • George Pentheroudakis
    • 1
  • George Lazaridis
    • 1
  • Nicholas Pavlidis
    • 1
  1. 1.Department of Medical OncologyIoannina University HospitalIoanninaGreece

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