Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal 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.

Caring for Pregnant Patients with Cancer: A Framework for Ethical and Patient-Centred Care

“…Breast cancer [19,20] Surgery (safe throughout pregnancy), radiotherapy (contraindicated in pregnancy), chemotherapy (second and third trimester), hormonal/endocrine therapy (contraindicated), immunotherapy (contraindicated, PD-1/PD-L1 pathway could result in immune response against the foetus), targeted therapy (contraindicated with exception of trastuzumab, which may be used in the first trimester under close monitoring).…”

Immune plasticity in pregnancy-associated breast cancer tumorigenesis

“…Normal human pregnancy and cancer share a variety of proliferative, invasive, and immune tolerance mechanisms (Margioula-Siarkou et al ., 2023). The latter represents a hallmark for both conditions considering that tumors develop numerous immunosuppressive mechanisms to evade immune clearance similar to those that can be normally seen during fetal tolerance and postpartum mammary involution (Holtan et al ., 2009).…”

“…This condition accounts for around 4% of breast cancers in women of childbearing age and generally exhibits an aggressive clinical course requiring complex and delicate clinical management (Chelmow et al ., 2020; Poggio et al ., 2020; Blundo et al ., 2021). Existing data in the literature suggest that when patients with PrBC receive standard treatments, they experience comparable clinical outcomes with other young non-pregnant patients (Anderson et al ., 2022); however, caution is being paid on the biological mechanisms inhibited by the therapeutical regimens in order to preserve maternal and fetal health avoiding adverse outcomes (Margioula-Siarkou et al ., 2023).…”

Survival probabilities and prognostic factors of pregnancy-associated breast cancer in Malaysian women

“…As summarized in a recent review [ 5 ], potential mechanisms that might be associated with the pathophysiology of PABC are hormonal changes during pregnancy (increased levels of estrogen and progesterone), enhanced inflammatory responses, pregnancy-associated immune tolerance, high oncogene expression, and breast involution, which can prompt and enhance oncogenic developments.…”