Our team’s reading recommendation for this month goes to “A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer”
by Changxia Shao et al. from Merck & Co.[i], an interesting paper just published in the journal of oncology that presents a meta-analysis on a total of 135 eligible studies to evaluate the prognostic value of BRCAm, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types.
PARP inhibithors (PARPi) can be an effective treatment for individuals who have variants in genes that are involved in DNA repair (HRR genes), such as BRCA1/2 but also beyond. Efforts to further identify genome-wide synthetic lethal vulnerabilities to this class of drugs led to the identification of other HRR gene mutations (HRRm) and characterization of homologous recombination deficient (HRD) cell state that renders cancer cells sensitive to PARPi. However, little is known regarding whether the presence of these genetic alterations alone affects overall survival (OS) in cancer patients not treated with PARPi or immunotherapy.
The paper presents a systematic review and meta-analysis to examine the prognostic value of these biomarkers across multiple cancer types in predicting OS in cancer patients treated with chemotherapy or targeted therapy other than PARPi. The following results were observed:
- Breast cancer patients with BRCA1/2m had a similar OS to those with wild-type BRCA1/2 (BRCA1/2 wt) across 18 studies
- Ovarian cancer patients with BRCA1/2m had a significantly longer OS than those with BRCA1/2 wt across 24 studies
- For other cancer types (in particular for prostate and pancreatic cancers), in the few studies that were analysed, the OS was similar between patients with BRCA1/2m and BRCA1/2 wt
It concludes that:
“Given the significantly improved outcomes following treatment with PARPi and augmented synthetic lethality to platinum agents in patients with tumors that have markers of HRD, the development and standardization of biomarker assays could have important clinical implications in discovering novel synthetic lethal combination therapies to improve outcomes for cancer patients.”
The study highlights the importance of improving the diagnostic precision and therefore the selection of the most effective treatments in clinical oncology.
The BRaCA panel is one of the products from the 4bases’ portfolio aiming at supporting the clinical oncology community in reaching this very important objective.
More information can be found on: 4bases.ch/braca-panel
#breastcancer ; #genetics ; #ngs ; #DNAsequencing
[i]Shao C, Chang MS, Lam FC, Marley AR, Tang H, Song Y, Miller C, Brown M, Wan I, Han J, Adeboyeje G. A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer. J Oncol. 2022 Jul 20;2022:5830475. doi: 10.1155/2022/5830475. PMID: 35909902; PMCID: PMC9328957.
