Introduction: Trisomy 21 (T21) is the most common chromosomal abnormality and one of the main causes of intellectual disability. The tumor profile of T21 patients is characterized by the low frequency of solid tumors including breast cancer.

Methods: The objective of this work was to analyze the literature to find possible clues for the low frequency of breast cancer in T21 persons with a focus on one hand to the various risks and protective factors against breast cancer for women T21, and on the other hand to changes in the expression of different genes located on chromosome 21.

Results: T21 women have hormonal and societal risk factors for breast cancer: frequent nulliparity, lack of breastfeeding, physical inactivity and high body mass index. The age of menopause, earlier in T21 women, has a modest protective effect against breast cancer. The low rate of breast tumors in T21 women is probably mainly linked to the reduced life expectancy compared to the general population (risk of death before the age of onset of the majority of breast cancers) and the presence of a third chromosome 21, characterizing the disease. It might lead to the increased expression of a number of genes contributing directly or undirectly to tumor suppression, decreased tumor angiogenesis and increased cell apoptosis. Moreover, changes in the mammary stroma of persons T21 could have an inhibitory role on the development of breast tumors.

Conclusion: The low frequency of breast cancers for T21 patients may not only be explained by hormonal and societal factors, but also by genetic mechanisms which could constitute an interesting axis of research in breast cancer.