Pregnancy-associated breast cancer and metastasis

The protective effect of pregnancy is neither immediate nor constant — a transient increase in breast cancer risk occurs with pregnancy in women of all ages. The risk of pregnancy-associated breast cancer is greatest in older first-time mothers.Pregnancy-associated breast cancer has a higher mortality rate because metastasis is common. Possible reasons for breast cancer metastasis with pregnancy include the promotional effects of pregnancy-associated hormones and a delay in diagnosis in recently-pregnant women. However, existing data indicate that these factors do not account for the high mortality associated with pregnancy-associated breast cancer.Following pregnancy and lactation, the mammary gland regresses to its pre-pregnant state by a tissue remodelling process known as involution. The microenvironment of the involuting mammary gland shares attributes with inflammation and wound healing.Because pro-inflammatory tissue environments can promote tumorigenesis, the involuting mammary gland might be tumorigenic. Candidate mediators of tumour cell progression during gland involution include an influx of activated immune cells, increased concentrations of matrix metalloproteinases, remodelling of mammary extracellular matrix with subsequent release of tumour-promoting growth factors and matrix fragments with bioactivity, and loss of basement-membrane barrier function.Under normal conditions of involution, pro-inflammatory pathways are activated, but the balance of pro- to anti-inflammatory signals is tipped towards suppression of overt inflammation.The presence of occult disease at the time of gland involution is anticipated to aggravate the tumour-promoting microenvironment by tipping the balance towards overt inflammation. So, women with occult disease at the time of pregnancy might be at an increased risk of tumour cell dissemination during mammary gland involution.As the average age of child-bearing continues to rise, the incidence of pregnancy-associated breast cancer and its associated high mortality rate are also anticipated to rise.