Медицинская библиотека · Annals of oncology : official journal of the European Society for Medical Oncology · 2025

Association between type and location of germline BRCA1/2 pathogenic or likely pathogenic variants with phenotype and prognosis in young patients with breast cancer: results from an international cohort study.

Toss A, Blondeaux E, Tenedini E, Bonamici L, Graffeo R, Livraghi L, Villarreal-Garza C, Bernstein Molho R, Kwong A, Balmana J, Wildiers H, Agostinetto E, Phillips K A, Pogoda K, Renaud T, Rousset-Jablonski C, Ferrari A, Moore H C F, Peccatori F A, Paluch-Shimon S, Fruscio R, Micheri C, Wong S M, Cui W, Vernieri C, Lee M K, De Marchis L, Couch F J, Del Mastro L, Puglisi F, Meireles P A, Kemp Z, Matikas A, Plichta J, Del Pilar Estevez-Diz M, Di Meglio A, Cichowska-Cwalinska N, Gianni C, Yerushalmi R, Sanchez-Bayona R, Mrinakova B, Matos L, Bianchini G, Caleffi M, Krivokuca A, Abdou Y, Mariño-Mariño M, Parokonnaya A, Okano M, Antone N, Saavedra C, Sonnenblick A, Duchnowska R, Pais H L, Harbeck N, Cortesi L, Delucchi V, De Angelis C, Lambertini M

СтатьяМногоцентровое исследованиеПеревод в очереди

Аннотация

BACKGROUND

The clinical implications of specific pathogenic and likely pathogenic variant (LP/PV) types and locations in the BRCA1 orBRCA2 tumor-suppressor genes remain to be elucidated.

PATIENTS AND

METHODS

The BRCA BCY Collaboration (NCT03673306) is an international, multicenter, hospital-based, retrospective cohort study that included BRCA carriers diagnosed with invasive breast cancer at the age of ≤40 years between January 2000 and December 2020. In this analysis, only patients with detailed available information on LP/PVs in the BRCA genes were included. Clinicopathological features and survival outcomes [disease-free survival (DFS) and overall survival (OS)] were investigated according to LP/PV type [insertion-deletion (indel) versus single-nucleotide variants versus copy number variations; truncating versus non-truncating LP/PVs; frameshift versus nonsense versus splicing versus missense LP/PVs] and location (exon involved and protein domain).

RESULTS

Out of 5660 patients from 109 centers worldwide, 3294 were eligible for the present analysis (2080 BRCA1 and 1214 BRCA2). The distribution of LP/PV types showed no meaningful associations with baseline clinicopathological features. BRCA1 protein-truncating variants were associated with worse OS compared with non-truncating variants [hazard ratio (HR) 2.00, 95% confidence interval (CI) 1.17-3.41]. A similar, though non-significant, trend was observed for BRCA2. Missense variants were linked to better OS for both BRCA1 (HR 0.48, 95% CI 0.28-0.84) and BRCA2 carriers (HR 0.17, CI 0.03-0.96). Regarding variant location, BRCA1 LP/PVs outside exons 2, 10, and 19 were associated with improved OS. In BRCA2, LP/PVs located in exons 15-26 and other regions were linked to worse DFS compared with those in exon 10, with no significant differences in OS.

CONCLUSIONS

This study advances our understanding of the influence of specific types of BRCA LP/PVs on breast cancer characteristics and outcomes. A deeper understanding of these variant-specific features will drive future research and support the development of tailored clinical strategies based on individual BRCA variant.

Для цитирования: Toss A, Blondeaux E, Tenedini E, Bonamici L, Graffeo R, Livraghi L, Villarreal-Garza C, Bernstein Molho R, Kwong A, Balmana J, Wildiers H, Agostinetto E, Phillips K A, Pogoda K, Renaud T, Rousset-Jablonski C, Ferrari A, Moore H C F, Peccatori F A, Paluch-Shimon S, Fruscio R, Micheri C, Wong S M, Cui W, Vernieri C, Lee M K, De Marchis L, Couch F J, Del Mastro L, Puglisi F, Meireles P A, Kemp Z, Matikas A, Plichta J, Del Pilar Estevez-Diz M, Di Meglio A, Cichowska-Cwalinska N, Gianni C, Yerushalmi R, Sanchez-Bayona R, Mrinakova B, Matos L, Bianchini G, Caleffi M, Krivokuca A, Abdou Y, Mariño-Mariño M, Parokonnaya A, Okano M, Antone N, Saavedra C, Sonnenblick A, Duchnowska R, Pais H L, Harbeck N, Cortesi L, Delucchi V, De Angelis C, Lambertini M. Association between type and location of germline BRCA1/2 pathogenic or likely pathogenic variants with phenotype and prognosis in young patients with breast cancer: results from an international cohort study.. Annals of oncology : official journal of the European Society for Medical Oncology. 2025. DOI: 10.1016/j.annonc.2025.11.004.

Предметные рубрики MeSH

Humans Female Breast Neoplasms BRCA2 Protein BRCA1 Protein Germ-Line Mutation Adult Prognosis Retrospective Studies Phenotype Young Adult

Подготовка и перевод публикации

Обработка статьи · этапы, ошибки и управление

Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.