CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer Breast cancer, the most common cancer type in women, is affecting many lives. In the European Union, women have a lifetime risk of 1 in 8 for developing breast cancer. The incidence of this cancer is increasing over recent years. Amidst this challenge, a promising new treatment strategy emerges, the introduction of CDK4/6 inhibitors as adjuvant treatment for early stage breast cancer. This especially for the hormone receptor positive, HER2-negative subtype. This refers to the different types of receptors on the tumour tissue. This subtype accounts for approximately 70% of all breast cancer types. Breast cancer consists of cells that can grow in an uncontrolled way. One of the most daunting aspects of breast cancer is the potential for recurrences. Even after patients enter a state of remission, meaning that no visible cancer cells can be detected, breast cancer recurrences can still occur. After many years, a patient on remission could still have recurrences, meaning that not all malignant cells were gone. This forms a substantial medical and social problem. CDK4/6 inhibitors offer a spark of optimism in confronting this challenge. These medications work on targeting enzymes, namely CDK4 and CDK6, crucial to the cell cycle. By interfering on a fundamental level in the cell cycle, they inhibit tumour cells from proliferation. Three different types of CDK4/6 inhibitors are currently used in clinical practice, palbociclib, ribociclib and abemaciclib. All three of them have a different molecular point of action, thus causing differences in efficacy and side effects. These CDK4/6 inhibitors are already used in advanced breast cancer, where the tumour cells have spread beyond the breasts. This thesis evaluated their efficacy in early breast cancer. However, four major studies have been conducted, all with conflicting results. In this thesis, the data of the conflicted studies were analysed and compared. A comprehensive view of the effectiveness of these drugs in early breast cancer will be provided. Given the widespread impact of breast cancer, research is highly needed. The potential of these CDK4/6 inhibitors in early treatment is profound. Breast cancer has a disastrous impact on patients’ lives, not to mention the mental stressors and uncertainties patients have to endure. If patients are prescribed a drug that could possibly prevent recurrences, it could significantly relieve this mental burden. If CDK4/6 inhibitors prove effective in preventing recurrences, they may contribute to an enhanced quality of life for individuals diagnosed with breast cancer. Selecting therapies with fewer side effects is also crucial in improving the patients’ experience. Since their approval for use in the advanced setting in 2017, 70% of patients received these drugs. This led to a significantly decreased use of chemotherapy. The CDK4/6 inhibitors could have the same impact in early setting, potentially reducing the need for more aggressive treatments. This type of medication can be administered from home, leaving patients to have more freedom and even further continue working and contributing to society while feeling more empowered. There could be an economic impact since the price of these drugs is high and governments will have to decide on their reimbursement policies. This can lead to situations of social inequality between different healthcare institutions. On the positive side, the reduction of breast cancer recurrences could lower healthcare resource usage. As highlighted by the conflicting studies, a further need for individualisation of cancer therapy is growing. This is the subject of many future studies. This by selecting subgroups in research that might benefit from a CDK4/6 inhibitor. Additionally, the need for biomarkers to detect patients’ response to a CDK4/6 inhibitor will also be off crucial value. Future research is highly needed to uncover these biomarkers. In conclusion, the incorporation of CDK4/6 inhibitors to standard of care therapy for early stage breast cancer represents a promising chapter in the ongoing battle against breast cancer. These medications provide patients and healthcare workers with a tool to increase the changes of long-term remission. This marks a significant step forward in the combat against this disease. Student: Helena Vansteenkiste Promotor and Copromotor: Prof. Dr. Hannelore Denys, Dr. Aglaja De Pauw