BRCA2 (Breast cancer 2, early onset)

Our findings support a role of rare pathogenic germline variants involved in DNA damage repair, and particularly those predisposing to breast cancer, in the immune landscape of breast tumors. These insights may help guide the development of immunomodulatory strategies for breast cancer prevention and treatment.

The successful implementation of HRR gene testing depends not only on access to sequencing technologies but also on the establishment of a comprehensive pre- and post-analytical framework. The aim of this document is to establish a multidisciplinary expert opinion consensus on the optimisation of molecular assessment of BRCA1/2 and other HRR gene alterations in metastatic prostate cancer to support implementation in clinical practice.

In patients with cervical cancer, BRCA testing holds important clinical value, particularly for the management of those with a significant family history of malignancy or confirmed hereditary predisposition. Appropriate genetic counseling plays an essential role in guiding preventive strategies, facilitating early diagnosis, and supporting informed decision-making regarding potential prophylactic interventions.

Several patients carried multiple deleterious variants, suggesting a possible polygenic contribution to EOBC predisposition. These findings expand the spectrum of rare DNA repair gene variants observed in BRCA1/2-negative early-onset breast cancer and provide candidate variants for further investigation, rather than establishing definitive causal associations.

We present a novel synthetic biology approach that leverages hepatic sEV production for the systemic delivery of siRNA to breast cancer. This strategy effectively suppresses tumor growth in BRCA2-deficient mice models and offers a promising therapeutic alternative with potential to overcome the limitations of current PARP inhibitor treatments for breast cancer.

Ongoing research into the fallopian tube origin of high-grade serous ovarian cancer has prompted research that may expand risk-reducing surgical options. Collectively, these innovations mark a transformative era in hereditary cancer care, emphasizing access, multidisciplinary integration, and the urgent need for novel delivery models to ensure that the benefits of genetic testing reach all individuals at risk.

Rapid demonstrated high genetic testing uptake and effective integration into oncology workflows, enabling timely treatment decisions. Although the program optimized resource use and reduced barriers, disparities in testing remain. Future efforts should address these inequities and evaluate the long-term impact of genetic testing on patient outcomes.

Our study demonstrates a substantial prevalence of DDR mutations and their association with inferior EGFR-TKI efficacy, highlighting the importance of genomic profiling of DDR mutations to identify this high-risk subpopulation in EGFR-mutant NSCLC.

These results suggest the scientific rationale for further clinical development of JPI-547 for treating both PARP inhibitor-sensitive patients and those resistant to first-generation PARP inhibitors in BRCA-mutated cancers.

The significance of these discoveries spread beyond BRCA1-mutant and BRCA2-mutant cancers: the synthetic lethal concept of the BRCA-PARP inhibitor effect highlighted the myriad levels of functional redundancy that exist in tumour cells and stimulated the search for other tumour-specific synthetic lethal effects that could be exploited therapeutically. Here we distill the learnings from the past two decades in this field.

Homologous recombinant deficient tumors are associated with the solid transitional-like morphology, with the BRCA1/2-mutated homologous recombinant deficient cases showing the strongest correlation. Genomic instability score alone may not fully capture the spectrum of homologous recombinant deficient-related phenotypes. The variation in solid transitional-like morphology features among BRCA1- or BRCA2-mutated, BRCA1/2- wild-type with homologous recombinant deficient, and homologous recombinant proficient cases may reflect the diverse biological spectrum of different homologous recombination alterations.

In bladder and prostate cancer, novel insights into tumor biology have reshaped therapeutic strategies and supported the approval of targeted therapies, thereby enhancing patient care. Selecting appropriate molecular tests-such as FGFR screening in urothelial carcinoma and BRCA1/2 testing in prostate cancer-has become critical for guiding treatment decisions.