Background: Breast cancer (BC) is the most common cancer for women in the western world.From very few cases an extraordinary increase in BC was observed in the Inuit population of Greenland and Canada although still lower than in western populations.Previous data suggest that exposure to persistent organic pollutants (POPs) might contribute to the risk of BC.Rat studies showed that perfluorinated compounds (PFCs) cause significantly increase in mammary fibroadenomas.This study aimed at evaluating the association between serum levels of POPs / PFCs in Greenlandic Inuit BC cases and their controls, and whether the combined POP related effect on nuclear hormone receptors affect BC risk.Methods: 31 BC cases and 115 controls were sampled during 2000-2003 from various Greenlandic districts.The serum levels of POPs, PFCs, some metals and the combined serum POPs related effect on estrogen-(ER), androgen(AR) and Aryl hydrocarbon-receptor (AhR) transactivity were determined.Independent student t-test was used to compare the differences and the odds ratios were estimated by unconditional logistic regression models.Results: We observed for the very first time a significant association between PFC serum levels and the risk of Greenlandic Inuit BC cases.The BC cases also showed a significantly higher concentration ofpolychlorinated biphenyls at the highest quartile, a higher frequency of subject samples with significant POP related hormone-like agonistic ER and AR transactivity, whereas AhR toxic equivalent was lower in cases.Conclusions: The level of serum POPs, particularly PFCs, might be risk factors in the development of BC in lnuit.Hormone disruption by the combined serum POP related xenoestrogenic and xenoandrogenic activities may contribute to the risk of developing breast cancer in Inuit.Further investigations are needed to document these study conclusions.