BRCA2 mutation

P=N/A, N=400, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

P=N/A, N=518, Active, not recruiting, ETOP IBCSG Partners Foundation | Trial primary completion date: Dec 2025 --> May 2025

BRCA1 and BRCA2 germline profiling based on next-generation sequencing technology among Egyptian breast cancer female patients revealed 135 germline variations -104 intronic and 31 exonic, respectively. Among the exonic variants; 13 were newly reported mutations. Hence further study is required to enhance mutational analysis which may benefit clinical system.

After progression on androgen deprivation therapy, abiraterone, enzalutamide, and docetaxel, genomic profiling identified a pathogenic BRCA2 alteration. Olaparib induced an undetectable prostate-specific antigen within three months, maintained for over 27 months, with complete resolution of bone metastases. This case highlights the potential for durable responses to olaparib and the importance of early genomic testing.

These findings provide a biological rationale to explore AKT1/HER2-targeted combinations with PARP inhibition in future studies for gBRCA-mutated breast cancer and provide the first evidence of PIK3CA-gBRCA mutual exclusivity in Chinese patients. The elevated HRD scores further underscore the presence of homologous recombination deficiency in the gBRCA group.

Regarding "druggable markers," DLL3 was expressed in 66% of tumors and PD-L1 in 17.4%. Detailed analyses of different prognostic and predictive markers are needed to better understand EP-SCNC biology and create more personalized therapy to improve patient prognosis.

Our comprehensive findings underscore the clinical significance of BRCA1/2 mutations in gastric cancer, advocating for further research to elucidate their mechanistic implications and therapeutic opportunities.

We conclude that low dose DNA methyltransferase inhibition can cooperate with low dose PARP inhibition to increase DNA damage predominantly in cells with HRR deficiencies, ultimately producing more cell death than in HRR proficient tumors. We predict that clinical benefit will more likely be apparent in patients with DNA repair defective tumors and are focusing clinical exploration of this drug combination in these patients, with the goals of enhancing tumor cell death at minimal toxicities.

Yet, published research on intensive screening of women at high breast cancer risk has largely ignored these outcomes, leaving patients, providers, and guideline developers lacking the evidence needed for best practice. Outcomes research is both feasible and urgently needed to inform care decisions and health policy for this patient population.

Evidence was reviewed from controlled clinical trials in which eribulin, vinorelbine, capecitabine, gemcitabine, gemcitabine plus carboplatin, fam-trastuzumab-deruxtecan, sacituzumab govitecan, olaparib, and talazoparib were used in the second-line treatment for metastatic breast cancer, either as study drugs or as comparators. Exploratory data for fam-trastuzumab-deruxtecan suggest a survival benefit in human epidermal growth factor receptor 2-low, hormone-receptor-negative patients, but further solid evidence is required. Other chemotherapies with lower European Society for Medical Oncology-Magnitude of Clinical Benefit Scale scores may continue to be useful in highly selected patients.

P2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P=N/A, N=200, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: May 2028 --> May 2030 | Trial primary completion date: May 2026 --> May 2028