Targeting postlactational involution signaling pathways as a chemopreventive strategy against breast cancer
Alejandro Jiménez Navas
Centro de Investigación del Cáncer. Universidad de Salamanca - CSIC
Breast cancer is the second most commonly diagnosed tumor worldwide and the leading cause of cancer-related mortality in women. In 2022, approximately 2.3 million new cases were reported, ranking second only to lung cancer in incidence. The disease caused over 600,000 deaths, making it the fourth deadliest cancer overall. Among women, breast cancer accounts for one in four cancer diagnoses and one in six cancer-related deaths. In Spain, it has the highest incidence, mortality, and prevalence rates among women, with over 34,000 new cases and more than 6,000 deaths recorded in 2022. Although survival rates remain high, breast cancer continues to impose a significant physical, psychological, economic, and social burden. By 2050, the incidence is projected to rise to 3.5 million cases, with over 1.1 million deaths.
One of the most significant risk factors is reproductive history. Early pregnancy reduces the risk of breast cancer, especially if it occurs before the age of 20. However, if the first pregnancy happens after the age of 35, the protective effect decreases. Additionally, there is a temporary risk of developing pregnancy-associated breast cancer, which can appear up to 10 years later, with a higher risk if pregnancy occurs after 35. In recent decades, the trend of delaying the first pregnancy has contributed to the increase in breast cancer cases.
For high-risk women, such as those carrying BRCA1/2 gene mutations, preventive strategies like bilateral mastectomy are recommended. On the other hand, chemoprevention using medications like tamoxifen and raloxifene is available. However, these drugs have severe and prolonged side effects, which leads many women to avoid or discontinue treatment.
In this context, the present study explores chemopreventive strategies aimed at enhancing the post-lactation involution process by interfering with the pathways that regulate it, specifically the JAK2/STAT5 pathway. This approach aims to strengthen the protective effects of pregnancy on breast cancer development, potentially lowering the risk associated with this tumor type.