Gestational Breast Cancer – a Review of Outcomes, Pathophysiology, and Model Systems

Abstract

The onset of pregnancy marks the start of offspring development, and represents the key physiological event that induces re-organization and specialization of breast tissue. Such drastic tissue remodeling has also been linked to epithelial cell transformation and the establishment of breast cancer (BC). While patient outcomes for BC overall continue to improve across subtypes, prognosis remains dismal for patients with gestational breast cancer (GBC) and post-partum breast cancer (PPBC), as pregnancy and lactation pose additional complications and barriers to several gold standard clinical approaches. Moreover, delayed diagnosis and treatment, coupled with the aggressive time-scale in which GBC metastasizes, inevitably contributes to the higher incidence of disease recurrence and patient mortality. Therefore, there is an urgent and evident need to better understand the factors contributing to the establishment and spreading of BC during pregnancy. In this review, we provide a literature-based overview of the diagnostics and treatments available to patients with BC more broadly, and highlight the treatment deficit patients face due to gestational status. Further, we review the current understanding of the molecular and cellular mechanisms driving GBC, and discuss recent advances in model systems that may support the identification of targetable approaches to block BC development and dissemination during pregnancy. Our goal is to provide an updated perspective on GBC, and to inform critical areas needing further exploration to improve disease outcome.

Host response during unresolved urinary tract infection alters mammary tissue homeostasis through collagen deposition and TIMP1

“…While such signals of delayed involution may be influenced by combinatorial systemic responses to UTI, changes to mammary microenvironment, and overall cellular states, it illustrates that infections that women are at a higher risk to develop during and after pregnancy could impact the usually tightly controlled process of tissue reconstruction post-lactation. Interestingly, disruption of post-pregnancy/lactation tissue remodeling may provide a niche for oncogenic initiation and malignant outgrowth, and therefore representing a possible alteration that contributes to the incidence of post-partum breast cancer 58,59 .…”

Host response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1

“…Such signals of delayed involution may be influenced by combinatorial systemic responses to UTI, changes to mammary microenvironment, and overall cellular states, thus illustrating that infections that women are at a higher risk to develop during and after pregnancy could impact the tightly controlled process of tissue reconstruction post-lactation. Importantly, disruption of post-pregnancy/lactation tissue remodeling may provide a niche for oncogenic initiation and malignant outgrowth, and therefore representing a possible alteration that contributes to the incidence of post-partum breast cancer 58 , 59 .…”