Breast cancer, placenta and pregnancy

Abstract

Background: Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Tumours often present characteristics of high malignancy and are hormone receptor negative/HER2 positive or triple negative. In general, pregnancy, including the postpartum period, is associated with a transiently increased risk of developing breast cancer but followed by a long-lasting protective period. Placental metastases are very rare and, thus far, breast cancer metastases in the foetal compartment have not been described. To discuss these apparently contradictory observations, this narrative review resumes immunological and hormonal alterations during pregnancy potentially affecting breast cancer risk as well as tumour growth and behaviour.

Observations: Upregulation of breast cancer-associated genes involved in immunological and reproductive processes has been observed in parous women and is potentially responsible for a transiently increased risk in pregnancy. In contrast, maternal immunisation and immunoglobulin production against antigens expressed on trophoblast cells, such as specific glycosylation patterns of mucin-1 or RCAS1-associated truncated glycans, seem to prevent breast cancer development in later years. Animal and human studies indicate that T cells are involved in these processes. Several placenta-derived factors, especially kisspeptin, have direct anti-tumour effects. The pregnancy-related increase of estrogen, progesterone, and other hormones influence growth and characteristics of breast cancer while the role of further placenta-secreted factors is still controversially discussed.

Conclusion: Several factors and cells are involved in altered breast cancer risk during and after pregnancy and have potential for developing novel treatment strategies in future.

Keywords: Breast cancer; Estrogen; Foetal antigen hypothesis; Mucin; Placenta; Pregnancy; Progesterone; Trophoblast cells.