Why do some breast cancers diagnosed after pregnancy seem more formidable than others? A team from the Institut Pasteur provides the beginnings of an answer, by linking these postpartum breast cancers to a breast repair mechanism which can backfire. The study focuses on what happens to the mammary gland immediately after childbirth.
Postpartum breast cancers: a high-risk moment after pregnancy
In France, it is estimated that 5,000 to 6,000 women develop postpartum breast cancer each year, generally between 5 and 10 years after giving birth. Several studies show that these cancers are associated with a higher risk of metastasis and lower survival than those diagnosed outside this period, regardless of the hormone receptor status of the cancer cells. The higher the maternal age at the time of pregnancy, the more this risk increases.
After pregnancy and then breastfeeding, the mammary gland reorganizes in depth to return to its initial state, a process called postpartum involution, which resembles the healing mechanism. This process results in the destruction of millions of alveolar epithelial cells, the invocation of immune cells, the restructuring of the extracellular matrix, and renewal by fat cells. This is an important physiological event but also a delicate period.
The inflammation caused by involution temporarily but significantly increases the risk of postpartum breast cancer.
Senescence, these “worn” cells which repair the breast after childbirth…
To understand what is happening then, researchers from the Cellular Plasticity in Age-Related Pathologies unit studied the mammary glands of involving mice. They highlighted the presence of so-called senescent cells, mainly milk-producing cells. These cells have stopped dividing but remain active and orchestrate tissue remodeling by recruiting macrophages to clean and rebuild. “These results show that senescence is not simply an epiphenomenon, but a key player in complete tissue remodeling of the mammary gland during involution – a remarkable reconstruction without scarring or lasting damage“, summarized Aurélie Chiche, first author of the study, in a press release from the Institut Pasteur.
…and which facilitate the occurrence of cancer
But this senescence therefore has a double face: useful for repairing a breast damaged by the end of breastfeeding, it also creates an environment which helps cancer cells to adapt, escape from the breast and then colonize other organs. Senescent cells increase the flexibility of cancer cells through the substances they release. This allows cancer cells to better adjust to changes in their environment, thus facilitating their survival and dissemination throughout the body.
Towards preventive treatments against postpartum breast cancer?
In mice, eliminating these senescent cells during involution delayed the appearance of tumors and reduced metastases, a preventive treatment avenue that is still distant but promising for future young mothers.
“Our results suggest that a targeted intervention to modify senescent cells during mammary gland involution could reduce the risk of postpartum breast cancer” declares Han Li, main author of the study, head of the Cellular Plasticity in Age-Related Pathologies Unit at the Institut Pasteur.
By deepening the understanding of these mechanisms, researchers hope to develop new preventive interventions to combat a form of cancer that constitutes an urgent medical need.