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 nonsignificant 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.

Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer.

Additional information FundingThe clinical trial was funded by Lytix Biopharma AS.

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