Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal Adverse Outcomes

SIMPLE SUMMARY: Pregnancy-associated breast cancer (PABC) is mainly defined as breast cancer diagnosed during the gestational period or in the first year after birth. Significant differences are detected between PABC and non-pregnancy-associated breast cancer, in terms of epidemiology, clinical manifestations, diagnostic and therapeutic management, and, most importantly, in biological behavior and pathophysiological basis. Hormonal and immune changes during pregnancy, breast involution and altered gene expression are recognized as potential contributors to the pathogenesis of PABC. There is considerable scientific interest in the prognosis of PABC, since various reported adverse maternal and fetal outcomes are induced by PABC, such as reduced maternal survival compared to non-pregnant patients with breast cancer, as well as obstetrical complications (predominately preterm delivery), fetal complications (mainly prematurity-induced neonatal diseases) and fetal malformations as a result of treatment administered during gestational period. Currently, there are no long-term adverse outcomes reported for children born from women with PABC who received treatment during pregnancy. The longitudinal observation of PABC survivors and their children may reveal new, currently undocumented short- and long-term complications and adverse outcomes. ABSTRACT: Breast cancer is a common type of cancer diagnosed during pregnancy, with increasing incidence over the last years, as more women choose to delay childbearing. Compared to breast cancer in general population, pregnancy-associated breast cancer (PABC) is significantly different in its terms of epidemiology, diagnostic and therapeutic management, while it exhibits particularly aggressive behavior, deriving from its unique molecular and biological profile. Although not fully elucidated, the pathophysiological basis of PABC can be traced back to a combination of hormonal and immune changes during pregnancy, breast involution and altered gene expression. There is considerable controversy in the existing literature about the influence of PABC on pregnancy outcomes, regarding both short- and long-term effects on maternal and fetal/neonatal health. The majority of PABC patients have advanced-stage disease at initial diagnosis and face a significantly poorer prognosis, with decreased survival rates. The most commonly reported adverse obstetrical–fetal events are preterm delivery and prematurity-associated neonatal morbidity, while other neonatal treatment-associated complications might also occur, even when safe therapeutic options are applied during pregnancy. The objective of the present comprehensive review was to summarize current knowledge and up-to-date evidence about the pathophysiological, molecular and biological basis of PABC, as well as its association with adverse maternal, obstetrical, fetal and neonatal outcomes.