Nerone, M.; Rossi, L.; Condorelli, R.; Ratti, V.; Conforti, F.; Palazzo, A.; Graffeo, R. Beyond PARP Inhibitors in Advanced Breast Cancer Patients with Germline BRCA1/2 Mutations: Focus on CDK4/6-Inhibitors and Data Review on Other Biological Therapies. Cancers2023, 15, 3305.
Nerone, M.; Rossi, L.; Condorelli, R.; Ratti, V.; Conforti, F.; Palazzo, A.; Graffeo, R. Beyond PARP Inhibitors in Advanced Breast Cancer Patients with Germline BRCA1/2 Mutations: Focus on CDK4/6-Inhibitors and Data Review on Other Biological Therapies. Cancers 2023, 15, 3305.
Nerone, M.; Rossi, L.; Condorelli, R.; Ratti, V.; Conforti, F.; Palazzo, A.; Graffeo, R. Beyond PARP Inhibitors in Advanced Breast Cancer Patients with Germline BRCA1/2 Mutations: Focus on CDK4/6-Inhibitors and Data Review on Other Biological Therapies. Cancers2023, 15, 3305.
Nerone, M.; Rossi, L.; Condorelli, R.; Ratti, V.; Conforti, F.; Palazzo, A.; Graffeo, R. Beyond PARP Inhibitors in Advanced Breast Cancer Patients with Germline BRCA1/2 Mutations: Focus on CDK4/6-Inhibitors and Data Review on Other Biological Therapies. Cancers 2023, 15, 3305.
Abstract
We explored the outcomes of germline BRCA1/2 pathogenic/likely pathogenic variants (PVs/LPVs) in the endocrine-sensitive disease treated with first line standard of care cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Three studies retrospectively showed a reduction in overall survival (OS) and progression free survival (PFS) in gBRCA1/2m patients compared to both germinal BRCA1/2 wild type (gBRCA1/2wt) and to the untested population. Regarding the efficacy of PI3K inhibitors, there are no subgroup or biomarker analyses in which germinal BRCA status was explored. However, the biological interactions between the PIK3CA/AKT/mTOR pathway and BRCA1/2 at a molecular level could help us to understand the activity of these drugs when used to treat BC in BRCA1/2 PVs/LPVs carriers. The efficacy of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2 for HER2-low and HER2-positive (HER2+) BC, has been increasingly described. Unfortunately, data on T-DXd in HER2+ or HER2-low metastatic BC harboring germinal BRCA1/2 PVs/LPVs is lacking. Including germinal BRCA1/2 status in the subgroup analysis of the registration trials of this ADC would be of great interest, especially in the phase III trial DESTINY-breast04. This trial enrolled patients with HER2-negative (HER2-) and both HR+ and HR- metastatic disease, which can now be categorized as HER2-low. The HER2-low subgroup includes tumors that were previously classified as triple negative, so it is highly likely that some women were germline BRCA1/2 PVs/LPVs carriers and this data was not reported. Germline BRCA1/2 status will be available for a higher number of individuals with BC in the near future and data on the prognostic and predictive role of these PVs/LPVs is needed in order to choose the best treatment options.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
