Olaparib has been approved for the treatment of high-risk, early-stage breast cancer in patients with inherited faults in BRCA1 or BRCA2 genes and who have previously received chemotherapy treatment. In March 2022, the phase 3 OlympiA trial coordinated by the Breast International Group (BIG) revealed that adding Olaparib to standard treatments reduced the fatality rate of patients by 32%. Professor Andrew Tutt at King’s College London is Chair of the Steering Committee for the OlympiA trial. He and his colleagues were also involved in early laboratory research on PARP inhibitors such as Olaparib and their clinical development at the Breast Cancer Now Toby Robins Research Center, within the Division of Breast Cancer Research.
Olaparib exploits a specific weakness in cancers with mutations in BRCA1 and BRCA2 genes and is effective for patients with early-stage disease. Inherited mutations in BRCA1 and BRCA2 genes, which are responsible for DNA repair, are responsible for 5-10% of breast cancers. Researchers funded by Breast Cancer Now and Cancer Research UK demonstrated that cancer cells with BRCA1 or BRCA2 mutations are susceptible to PARP inhibitors. Early clinical trials of Olaparib showed that it was effective for patients with these kinds of mutations.
Researchers studied immune markers within tumor tissue and blood samples of early breast cancer patients whose cancer failed to respond to chemotherapy given to them prior to surgery. The research gives insight into the function of immune cells in patients with chemotherapy-resistant breast cancers. While chemotherapy might not kill cancer cells in these high-risk patients, immunotherapy, which helps the immune system to attack malignant cells, may provide a benefit.
Researchers funded by Breast Cancer Now found immune-related genes associated with NK cells were those associated with cell inhibition or exhaustion, which meant NK cells were unable to fight cancer cells. This knowledge could be used to develop specific immunotherapies for these high-risk patients. This would need to be investigated in future clinical trials. These findings are published in Clinical Cancer Research, a journal of the American Association for Cancer Research show that blood monitoring during chemotherapy may aid in early detection of chemotherapy response, potentially allowing for the tailoring of treatment prior to surgery.
Professor Andrew Tutt, Director of the Breast Cancer Now Toby Robbins Research Center at the ICR and Director of the Breast Cancer Now Research Unit at King’s College London, said: “Great strides have been made in harnessing immunotherapies to treat several types of cancer, but we need to do better to realize their potential for patients with breast cancer. This This exciting work advances our understanding of the interaction between cancer cells and the immune system during treatment, and why existing treatments work well for some patients, but not others. I hope this research will help us to enhance the anti-cancer immune response in breast cancer, particularly for patients whose cancer has not responded well to chemotherapy.”