Genetic mutation profile of Chinese HER2-positive breast cancers and genetic predictors of responses to Neoadjuvant anti-HER2 therapy.
Breast Cancer Res Treat
; 183(2): 321-332, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-32638235
ABSTRACT
PURPOSE:
Despite the therapeutic success of existing HER2-targeted therapies, tumors respond quite differently to them. This study aimed at figuring out genetic mutation profile of Chinese HER2-positive patients and investigating predictive factors of neoadjuvant anti-HER2 responses.METHODS:
We employed two cohorts. The first cohort was comprised of 181 HER2-positive patients treated at Guangdong Provincial People's Hospital from 2012 to 2018. The second cohort included 40 patients from the first cohort who underwent HER2-targeted neoadjuvant chemotherapy. Genetic mutations were characterized using next-generation sequencing. We employed the most commonly used definition of pathological complete response (pCR)-eradication of tumor from both breast and lymph nodes (ypT0/is ypN0).RESULTS:
In Chinese HER2-positive breast cancer patients, TP53 (74.6%), CDK12 (64.6%) and PIK3CA (46.4%) have the highest mutation frequencies. In cohort 2, significant differences were found between pCR and non-pCR groups in terms of the initial Ki67 status, TP53 missense mutations, TP53 LOF mutations, PIK3CA mutations and ROS1 mutations (p = 0.028, 0.019, 0.005, 0.013, 0.049, respectively). Furthermore, TP53 LOF mutations and initial Ki67 status (OR 7.086, 95% CI 1.366-36.749, p = 0.020 and OR 6.007, 95% CI 1.120-32.210, p = 0.036, respectively) were found to be predictive of pCR status.CONCLUSION:
TP53 LOF mutations and initial Ki67 status in HER2-positive breast cancer are predictive of pCR status after HER2-targeted NACT.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias de la Mama
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Biomarcadores de Tumor
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Proteína p53 Supresora de Tumor
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Receptor ErbB-2
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Terapia Neoadyuvante
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Pueblo Asiatico
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Mutación
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Breast Cancer Res Treat
Año:
2020
Tipo del documento:
Article
País de afiliación:
China