CHEK2 mutation

The patient underwent neoadjuvant chemothera- py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur- rence after ten months of follow-up. Although the CASR p.Glu755Asp variant's pathogenic role is unproven, emerging evidence links CASR overexpression with hER2-positive breast cancers, promoting tumor progression via calcium- dependent signaling pathways (PI3K/AKt, MAPK). This case highlights the potential role of CASR as a low-penetrance susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact.

P=N/A, N=200, Recruiting, University of Michigan Rogel Cancer Center

Offering genetic testing directly within the breast surgeon's clinic was associated with significantly higher completion rates compared with referral-based testing. Integrating genetic testing into surgical consultations may reduce logistical barriers and enable earlier use of genetic information in treatment planning.

P2, N=32, Active, not recruiting, Academic and Community Cancer Research United | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Aug 2026

These patients had a higher frequency of bilateral WT and a higher rate of abnormalities compared to patients without aberrations (56% vs. 25%, p = 0.002; and 86% vs. 25%, p < 0.0001, respectively). The detection of WT hereditary predisposing factors is crucial for treatment strategies and long-term patient surveillance.

P1, N=44, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

P2, N=51, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2026 --> May 2027

P2, N=88, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting

P1/2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=120 --> 35

Rate ratio (RR) analysis showed a significant risk for ATM (2.98), while overall RR indicated more than a two-fold increased CBC risk with radiotherapy (RR = 2.70 common-effect; 2.53 random-effects). Radiotherapy significantly increases contralateral breast cancer risk, particularly in ATM and CHEK2 carriers, emphasizing the importance of personalized genetic risk stratification in treatment decisions.

Further assessment of immunohistochemical, immunofluorescent, and flow cytometric data revealed that berry-derived nanoparticles are associated with the modulation of oncogenic transcription factors and linked to induced caspase-dependent execution-phase ROS-mediated apoptosis through pPAK1Thr212 dephosphorylation, downregulation of pPI3Kp85αγ(Tyr467/199)/pAKT1Thr450/mTOR signaling, and modulation of pJAK3Tyr785/STAT3 pathway supporting transcriptomic and transcriptional reprogramming of 4T1 treated cells. Together, our findings uncover a new strategy to capture berry-derived polyphenols required to regulate apoptosis, autophagy, immune response, and metastasis-related gene networks in breast cancer, thereby underscoring the therapeutic potential of functionalized AuNPs as delivery platforms for dietary phytochemicals.

Our findings and those described in the literature suggest that CHEK2 may play a role in the germline origin of childhood pre-B ALL in specific populations. However, this study provides preliminary evidence of pre-B ALL predisposition in Mexican children with CHEK2 GVs that needs replication in a larger cohort to obtain accurate estimations.