Clinical implication of tumor mutational burden in patients with HER2-positive refractory metastatic breast cancer

This study explored the clinical implications of tumor mutational burden (TMB) in a well-defined HER2-positive metastatic breast cancer (MBC) patient population who had been previously treated but had subsequent disease progression. Whole exome sequencing was performed on formalin-fixed paraffin-emb...

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Vydáno v:	Oncoimmunology Ročník 7; číslo 8; s. e1466768
Hlavní autoři:	Park, Song Ee, Park, Kyunghee, Lee, Eunjin, Kim, Ji-Yeon, Ahn, Jin Seok, Im, Young-Hyuck, Lee, Choonghoon, Jung, Hun, Cho, Soo Youn, Park, Woong-Yang, Cristescu, Razvan, Park, Yeon Hee
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Taylor & Francis 01.01.2018 Taylor & Francis Group
Témata:	Human epidermal growth factor receptor 2 (HER2) Long survival outcomes Metastatic breast cancer (MBC) Original Research Tumor mutational burden (TMB) whole exome sequencing (WES) Human epidermal growth factor receptor 2 (HER2) Metastatic breast cancer (MBC) Tumor mutational burden (TMB) Long survival outcomes whole exome sequencing (WES)
ISSN:	2162-402X, 2162-4011, 2162-402X
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Shrnutí:	This study explored the clinical implications of tumor mutational burden (TMB) in a well-defined HER2-positive metastatic breast cancer (MBC) patient population who had been previously treated but had subsequent disease progression. Whole exome sequencing was performed on formalin-fixed paraffin-embedded tumor samples and matched normal tissue. Among the 46 patients, 13 (28.3%) were estrogen receptor-positive and nine (19.6%) were progesterone receptor-positive by immunohistochemistry analysis. Twenty patients (43.5%) had recurrent MBC compared with de novo MBC (n = 26, 56.5%). Sixteen patients (34.6%) demonstrated more than 100 somatic non-synonymous SNV mutations, which was predefined as a high TMB. The median follow-up duration was 57.5 months. The median overall survival (mOS) differed significantly between low and high TMB status (44.9 months vs. 85.8 months, respectively, p = 0.016). In a multivariate Cox regression analysis, TMB was the only independent prognostic factor for good metastatic overall survival after adjusting for age and recurrence (Hazard ratio [HR] = 0.32, 95% confidence interval [CI], 0.103-0.998, p = 0.049). These data suggest that high TMB may be a prognostic marker for predicting good overall survival for patients undergoing conventional HER2-directed treatments and chemotherapy. Further, future clinical trials harnessing TMB may benefit by identifying an appropriate population who may have a favorable response to immunotherapy after recurrence following HER2-directed treatments.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Supplemental data for this article can be accessed on the publisher's website. SEP and KHP contributed equally to this work.
ISSN:	2162-402X 2162-4011 2162-402X
DOI:	10.1080/2162402X.2018.1466768