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Elucidating Therapeutic Molecular Targets in Premenopausal Asian Women with Recurrent Breast Cancers

Yap, Yoon-Sim and Singh, Angad and Lim, John and Ahn, J.H. and Jung, K.H. and Kim, J. and Dent, R.A. and Ng, R.C.H. and Kim, Sung-Bae and Chiang, Derek (2018) Elucidating Therapeutic Molecular Targets in Premenopausal Asian Women with Recurrent Breast Cancers. npg breast cancer, 4. p. 19.

Abstract

Breast cancer is an increasing problem in Asia, with a higher proportion of premenopausal patients who are at higher risk of recurrence. Targeted sequencing was performed on DNA extracted from primary tumour specimens of 63 premenopausal Asian patients who relapsed after initial diagnosis of non-metastatic breast cancer. The most prevalent alterations included: TP53 (65%); PIK3CA (32%); GATA3 (29%); ERBB2 (27%); MYC (25%); KMT2C (21%); MCL1 (17%); PRKDC, TPR, BRIP1 (14%); MDM4, PCDH15, PRKAR1A, CDKN1B (13%); CCND1, KMT2D, STK11, MLH1 (11%). Sixty of the 63 patients (95%) had at least one genetic alteration in a signaling pathway related to cell cycle or p53 signaling. The presence of MCL1 amplification, HIF-1-alpha transcription factor network pathway alterations and direct p53 effectors pathway alterations were independent predictors of inferior overall survival from initial diagnosis. Comparison with non-Asian premenopausal tumours in The Cancer Genome Atlas (TCGA) revealed a higher prevalence of TP53 mutations among HER2-positive cancers, and more frequent TP53, TET2 and CDK12 mutations among hormone receptor positive HER2-negative cancers in our cohort. Given the limited number of non-Asian premenopausal breast cancers that had relapsed in TCGA, we compared the frequency of mutations in our cohort with 43 premenopausal specimens from both TCGA and International Cancer Genome Consortium (ICGC) that had relapsed. There was a trend towards higher prevalence of TP53 mutations in our cohort. Certain genomic aberrations may be enriched in tumours of poor-prognosis premenopausal Asian breast cancers. The development of novel therapies targeting these aberrations merit further research.

Item Type: Article
Date Deposited: 10 Aug 2018 00:45
Last Modified: 10 Aug 2018 00:45
URI: https://oak.novartis.com/id/eprint/35525

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