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DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients.

ABSTRACT: Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues and assayed for differential methylation profiles using Illumina HumanMethylation450 BeadChips. The results were validated in an independent cohort of 70 primary TNBC samples. The expression of 16/38 TNBC-specific genes was associated with alteration in DNA methylation. Novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Altered methylation of 18 genes associated with lymph node metastasis were identified and validated. This study reveals the important role DNA methylation plays in altered gene expression of TNBC-specific genes and lymph node metastases. The novel insights into progression of TNBC to secondary disease may provide potential prognostic indicators for this hard-to-treat breast cancer subtype.

SUBMITTER: Mathe A

PROVIDER: S-EPMC5037364 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients.

Mathe Andrea A Wong-Brown Michelle M Locke Warwick J WJ Stirzaker Clare C Braye Stephen G SG Forbes John F JF Clark Susan J SJ Avery-Kiejda Kelly A KA Scott Rodney J RJ

Scientific reports 20160927

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 prima ...[more]

PMID: 27671774

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Project description:In this study, we aimed to evaluate axillary lymph node dissection (ALND) rates and prognosis in neoadjuvant chemotherapy (NCT) compare with neoadjuvant endocrine therapy (NET) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), lymph node (LN)-positive, premenopausal breast cancer patients (NCT01622361). The multicenter, phase 3, randomized clinical trial enrolled 187 women from July 5, 2012, to May 30, 2017. The patients were randomly assigned (1:1) to either 24 weeks of NCT including adriamycin plus cyclophosphamide followed by intravenous docetaxel, or NET involving goserelin acetate and daily tamoxifen. ALND was performed based on the surgeon's decision. The primary endpoint was ALND rate and surgical outcome after preoperative treatment. The secondary endpoint was long-term survival. Among the 187 randomized patients, pre- and post- neoadjuvant systemic therapy (NST) assessments were available for 170 patients. After NST, 49.4% of NCT patients and 55.4% of NET patients underwent mastectomy after treatment completion. The rate of ALND was significantly lower in the NCT group than in the NET group (55.2% vs. 69.9%, P=.046). Following surgery, the NET group showed a significantly higher mean number of removed LNs (14.96 vs. 11.74, P=.003) and positive LNs (4.84 vs. 2.92, P=.000) than the NCT group. The axillary pathologic complete response (pCR) rate was significantly higher in the NCT group (13.8% vs. 4.8%, P=.045) than in the NET group. During a median follow-up of 67.3 months, 19 patients in the NCT group and 12 patients in the NET group reported recurrence. The 5-year ARFS (97.5%vs. 100%, P=.077), DFS (77.2% vs. 84.8%, P=.166), and OS (97.5% vs. 94.7%, P=.304) rates did not differ significantly between the groups. In conclusion, although survival did not differ significantly, more NCT patients might able to avoid ALND, with fewer LNs removed with lower LN positivity.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01622361, identifier NCT01622361.

Dataset Information

DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients.

Publications

DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients.

Similar Datasets

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