The TP53 p.R337H Germline Variant and Breast Cancer: Prevalence from a Cohort Study and Structured Literature Review
The TP53 p.R337H germline variant is present in approximately 2% of breast cancer patients, with higher prevalence among patients diagnosed at age ≤45 years and in those with malignant phyllodes tumors.
BACKGROUND: The TP53 p.R337H germline variant is a Brazilian founder variant associated with Li‑Fraumeni syndrome and increased cancer susceptibility. Its prevalence among breast cancer (BC) patients remains incompletely characterized. The objective of this study is to evaluate the prevalence of the TP53 p.R337H germline variant among breast cancer (BC) patients through a cohort study and structured literature review. METHODS: One hundred BC patients from Hospital Universitário Antonio Pedro were interviewed and tested for the p.R337H variant using Sanger sequencing. A structured literature review was also conducted following PRISMA 2020 recommendations, searching PubMed, LILACS and SciELO for studies published between 1997 and 2025. Studies reporting zero detected cases were included to reduce selection bias. Due to heterogeneity among studies, no formal meta-analysis was performed and prevalence was reported descriptively. RESULTS: Of the 100 patients tested in our study, none had the variant (0.0%; 95% CI: 0.00‑3.62%). Of 46 identified records, 17 studies met the inclusion criteria. A total of 173 carriers were identified among 8,221 patients in the reviewed literature. Including our cohort, the combined sample totaled 8,321 patients, with a crude aggregated prevalence of 2.08% (95% CI 1.79‑2.41%). Higher prevalence was observed in patients diagnosed at ≤45 years and in malignant phyllodes tumors, while lower or absent prevalence was observed in unselected populations. CONCLUSION: The prevalence of the p.R337H variant among breast cancer patients varied across studies, according to age at diagnosis, patient selection criteria and geographic region. Larger multicenter studies are needed to better define its role in breast cancer risk assessment.
Knowledge of the prevalence of TP53 p.R337H among breast cancer patients informs genetic counseling, risk assessment and surveillance strategies for individuals and families in Brazil and other regions where the founder mutation is present.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.
Kapcsolódó jelek
- 20‑Year Risks of Breast‑Cancer Recurrence after Stopping Endocrine Therapy at 5 Years
- Breast Cancer: The good, the bad, and an important call to effective risk reduction strategies
- Clinical Trials in Cancer - Transforming Clinical Research in the United States - NCBI Bookshelf
- Decoding Clinical Trials in Metastatic Breast Cancer: Practical Insights for Optimal Therapy Sequencing
- The SURVIVE study (NCT05658172): Bringing breast cancer aftercare to the 21st century: Study protocol of a Phase III clinical trial comparing liquid biopsy guided vs. Standard of care surveillance for intermediate to high-risk breast cancer survivors - PMC