64 Breast cancer remains a significant health concern worldwide, with diverse molecular subtypes that necessitate personalised therapeutic approaches. Recent advances have highlighted the importance of molecular signatures in guiding breast cancer treatment. The PIK3CA gene mutation is one of these and has become an important part of figuring out how well targeted therapies work, especially in advanced breast cancer. This review explores the role of PIK3CA mutation detection in breast cancer and its implications for personalised treatment strategies. The findings were published in the journal Cancer Screening and Prevention. Breast cancer is a heterogeneous disease with various molecular signatures. This diversity necessitates a move away from traditional, one-size-fits-all treatment approaches towards more personalised therapies. Molecular analysis has identified distinct subtypes of breast cancer, each with unique genetic and molecular profiles. For instance, breast cancers expressing hormonal receptors can be treated with selective oestrogen receptor modulators (SERMs) or selective ooestrogen receptor degraders (SERDs), while those overexpressing the human epidermal growth factor receptor 2 (HER2)-neu gene benefit from anti-HER2 therapies. PIK3CA mutations are among the most common genetic alterations in breast cancer, present in approximately 30–40% of cases. These mutations lead to the activation of the PI3K/AKT signalling pathway, which promotes tumour growth and survival. The presence of PIK3CA mutations has significant implications for treatment, particularly in advanced stages of the disease. PIK3CA inhibitors, such as alpelisib, have shown promise in targeting this pathway, offering new hope for patients with PIK3CA-mutated breast cancer. Detecting PIK3CA mutations is critical for guiding treatment decisions in breast cancer. Patients with PIK3CA-mutated tumours are more likely to respond to PI3K inhibitors. This is especially important for people with advanced breast cancer that is hormone receptor-positive but not HER2-negative, since alpelisib plus SERDs like fulvestrant has been shown to work. However, it is essential to perform PIK3CA mutation testing before administering these therapies to ensure that patients are likely to benefit from the treatment. The integration of PIK3CA mutation testing into clinical practice has led to more personalised and effective treatment strategies. In the SOLAR-1 trial, people with advanced breast cancer that was PIK3CA-mutated, hormone receptor-positive, and HER2-negative who were given alpelisib plus fulvestrant had a much better chance of not progressing compared to people who were only given fulvestrant. This highlights the potential of targeted therapies to improve outcomes for specific subgroups of breast cancer patients. Despite the promising results, several challenges remain in the implementation of PIK3CA-targeted therapies. The development of resistance to PI3K inhibitors and the management of adverse effects are ongoing concerns. Additionally, the cost and accessibility of genetic testing can be barriers to widespread adoption. Future research should focus on overcoming these challenges, optimising combination therapies, and expanding the use of molecular testing to ensure that more patients can benefit from personalised treatment approaches.