Association Between Maternal Metabolic Disturbances During the First Pregnancy and Breast Density

Background. Breast cancer (BC) is the leading cause of cancer-related mortality in Chilean women. Mammographic density (BD) refers to the percentage of dense tissue of an entire breast. A high BD is the strongest known risk factor for BC. BD is partially modifiable; the first full term pregnancy (FFTP) reduces BD by average 12%. However, half of the women have no changes in BD after their FFTP and there is no evidence about factors that influence this lack of reduction. Identifying women who do not reduce BD after their FFTP and the potential factors associated with this lack of reduction would help to recognize a subgroup of women with greater vulnerability to BC. In some women, such as obese pregnant women of women with gestational diabetes (GDM), the metabolic adaptations are exaggerated and they show a disturbed metabolic milieu (characterized by hyperinsulinemia, hyperglycemia, higher C-reactive protein levels, and lower level of sex hormone-binding globulin), which may have biological effects on breast composition during this period of breast differentiation. Hypothesis. The hypothesis of the study proposes that the women with an altered metabolic milieu during their first full-term pregnancy will have higher breast density measured through DXA three months after cessation of lactation, when fully breast involution after pregnancy is achieved, compared to women without metabolic disturbances during their first full-term pregnancy. General Objective. The main goal is to evaluate in a cohort of primipara women the association between an altered metabolic milieu during pregnancy and breast density measured by DXA three months after breastfeeding cessation. Methods. One thousand pregnant women will be recruited at the beginning of their first pregnancy and evaluated at <15, 24-38 and 35-37 weeks during pregnancy and three months after breastfeeding cessation, as part of a longitudinal study. The main outcome will be breast composition measures three months after breastfeeding cessation. The main predictor will be metabolic status during pregnancy. Three months after breastfeeding cessation will record delivery data and a breast DXA exam will be carried out. Multiple linear regression models and generalized estimated equations will be used to explain this relationship. Expected results. The ultimate goal is to provide evidence on how to prevent breast cancer risk by reducing breast density.