Comprehensive review of pregnancy associated breast cancer: Clinical features, molecular characteristics and novel therapies.

Pregnancy-Associated Breast Cancer (PABC) accounts for pregnancy-related breast cancer (PrBC), occurring during pregnancy and the first postpartum year, and postpartum breast cancer (PPBC), arising up to 5-10 years after childbirth. It represents an increasingly oncological challenge as delayed childbearing trends extend maternal reproductive age. Occurring in approximately 1:3000 pregnancies, PABC accounts for 0.2-3.8 % of all breast cancer cases. PABC is often associated with aggressive clinic-biological characteristics, including higher prevalence of triple-negative subtypes, increased lymph node involvement, and more frequent advanced-stage presentation compared to age-matched non-pregnant controls. The complex mammary microenvironment during pregnancy, lactation, and postpartum involution undergoes extensive hormonal-driven remodeling that creates a biphasic landscape, initially providing a permissive environment for carcinogenesis while conferring long-term protective effects. The molecular mechanisms underlying this transformation remain incompletely understood and represent an active area of investigation. Molecular profiling of PABC reveals enhanced proliferative signaling pathways, metabolic reprogramming, tumor-promoting inflammatory responses, and compromised DNA damage repair mechanisms. While PABC shares similar genomic architecture with non-pregnancy-associated breast cancers, distinct gene expression signatures have been identified that may contribute to its aggressive phenotype. This comprehensive review examines the physiological breast changes occurring throughout the reproductive cycle and their relationship to PABC carcinogenesis. We analyze the molecular profile and clinicopathological features that distinguish PABC from conventional breast cancer, while addressing the therapeutic challenges posed by fetal safety considerations. Additionally, we evaluate the safety profiles of novel therapeutic agents during pregnancy and lactation, highlighting the critical need for new pregnancy-compatible treatment strategies.