Pregnancy Associated Breast Cancer: Defining the Risk and Targets for Intervention.
Virginia Borges, MD, University of Colorado Cancer Center
All women with a completed childbirth have an increased risk for the subsequent development of breast cancer regardless of the age at their first birth. This risk is highest in older mothers and those with a known family history. Moreover, breast cancers diagnosed subsequent to but in proximity of a recent childbirth have been identified in epidemiologic studies as having an increased risk for metastasis or death due to breast cancer, however much of the existing data is confounded by inclusion of cases diagnosed during pregnancy in the analysis. Pregnancy associated breast cancer (PABC) is a unique part of young women’s breast cancer that we propose includes two biologically distinct conditions: those diagnosed during pregnancy and those diagnosed post-partum. It is the dominant subset of post-partum PABC that encompasses both significantly larger numbers and the subset with higher breast cancer mortality. This presentation will review our work in preclinical models of PABC that has identified the “involution hypothesis”, where the normal physiologic event of weaning or post-partum breast involution as a highly pro-inflammatory milieu that drives tumor growth, proliferation and metastasis. Out data demonstrating that this “Involution Effect” can be abrogated with drug therapy targeting one of the normal physiologic pathways implicated in PABC tumor promotion will be presented. The remaining unmet research needs yet required for future translation into rationale and safe human clinical trials will be discussed. To this end, our data from a retrospective case controlled study, restricted to human postpartum PABC and controls, fully characterizing post-partum PABC by biologic subtype and known predictors for metastasis will be presented. We performed analyses to identify if the specific period of post-partum breast cancer diagnosis is associated with a higher risk for metastasis then young women’s breast cancer not complicated by recent pregnancy, as predicted by our animal model studies. We have identified a retrospective cohort of breast cancer diagnosed at age 45 or younger seen at the University of Colorado Hospital from 1981-2011. Pregnancy status was identified from medical record review. Clinicopathologic characteristics were obtained from pathology records and Her 2 neu testing performed centrally when needed. Outcomes data was obtained through the University of Colorado Tumor Registrar. Results will be discussed in the context of planning future prevention clinical trials.