BRCA1 mutation

Among patients with a reported germline mutation, 36.1% had a BRCA1, 62.9% a BRCA2 and 1.0% a PALB2 mutation. In summary, outcomes were comparable to those reported in pivotal trials despite later-line use of PARP-inhibitors in this analysis.

In another, an HR repair proficient tumor subclone lacking Shieldin 2 expression expanded during treatment and accounted for intrinsic resistance. Our findings highlight the need to determine intrinsic and anticipate acquired resistance pathways in treatment-naïve tumors and support combining PARPi with targeted agents to improve outcomes in the neoadjuvant setting.

Although no difference was found in the risk of CBC between BRCA 1/2 mutations, correspondence analysis revealed different contributing factors. For young BRCA carriers with a triple-negative subtype and poor pathologic parameters such as high grade and Ki-67 index, risk-reducing contralateral prophylactic mastectomy could be considered as a treatment strategy.

Moreover, molecular docking and dynamics studies were performed to elucidate the detailed binding mechanism of compound 18 with USP1. Taken together, this study presents a promising class of 1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide derivatives as novel USP1 inhibitors with significant therapeutic potential for the treatment of BRCA1-mutant cancers.

The patient was treated with four cycles of paclitaxel and carboplatin, followed by an additional four cycles of combination chemotherapy with durvalumab...Maintenance therapy with durvalumab and olaparib was initiated, and the patient has remained progression-free for 10 months...The case highlights the value of genomic profiling and germline testing for personalized treatment strategies. The successful use of platinum-based chemotherapy, immune checkpoint blockade and poly (ADP-ribose) polymerase inhibition to treat this HRD-positive, mismatch repair-proficient tumor demonstrates the potential of biomarker-driven therapy for UCS.

P2, N=120, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2026 --> Mar 2027

P1/2, N=117, Active, not recruiting, Cantargia AB | Trial primary completion date: Jun 2025 --> Apr 2026

This review synthesizes current knowledge on the unique tumor biology of breast cancer in young women, highlighting the need for precision oncology approaches that account for age-related tumor behavior. Enhanced characterization of this population may ultimately improve survival outcomes and quality of life for young women affected by breast cancer.

The mutational patterns affecting homologous recombination repair differ across gynecologic and breast cancers. Further research into cancer-specific HRD mechanisms is warranted.

Fusion transcript analysis identified 91 recurrent fusions, including novel partners with ERBB2, MED1, and CDK12, suggesting the possibility of unique molecular events. Interpretation and conclusions This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.

P2, N=21, Active, not recruiting, Rutgers, The State University of New Jersey | Recruiting --> Active, not recruiting | N=40 --> 21 | Trial completion date: Oct 2023 --> Sep 2027

In studies with lower risk of bias, germline BRCA2 mutations were more frequent in patients with ILC than IDC. Conversely, BRCA1 mutations are more frequently observed in IDC, particularly among younger patients and those with a positive family history of BC.