Simple prediction model for homologous recombination deficiency in breast cancers in adolescents and young adults.
Breast Cancer Res Treat
; 182(2): 491-502, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32488393
ABSTRACT
PURPOSE:
Homologous recombination deficiency (HRD), which influences the efficacy of PARP inhibitor- and platinum agent-based therapies, is a prevalent phenotype of breast cancer in adolescents and young adults (AYAs; 15-39 years old). However, HRD score, indicating HRD status, is not routinely assessed in the breast oncology clinic, particularly in patients without germline BRCA1/2 mutations. Hence, we sought to develop a model for determining HRD status based on genetic and clinicopathological factors.METHODS:
Subjects were our own cohort of 46 Japanese AYA breast cancer patients and two existing breast cancer cohorts of US and European patients. Models for prediction of the HRD-high phenotype, defined as HRD score ≥ 42, were constructed by logistic regression analysis, using as explanatory variables genetic and clinicopathological factors assessable in the clinical setting.RESULTS:
In all three cohorts, the HRD-high phenotype was associated with germline BRCA1/2 mutation, somatic TP53 mutation, triple-negative subtype, and higher tumor grade. A model based on these four factors, developed using the US cohort, was validated in the Japanese and European AYA cases area under the receiver operating characteristic curve [AUC] was 0.90 and 0.96, respectively. A model based on three factors excluding germline BRCA1/2 mutation also yielded high-predictive power in cases from these two cohorts without germline BRCA1/2 mutations AUC was 0.92 and 0.90, respectively.CONCLUSIONS:
The HRD-high phenotype of AYA breast cancer patients can be deduced from genomic and pathological factors that are routinely examined in the oncology clinic, irrespective of germline BRCA1/2 mutations.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Biomarcadores Tumorais
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Recombinação Homóloga
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Inibidores de Poli(ADP-Ribose) Polimerases
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Modelos Genéticos
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
País/Região como assunto:
America do norte
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Asia
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Europa
Idioma:
En
Revista:
Breast Cancer Res Treat
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão