Dataset Information

Concordance of genomic alterations between primary and recurrent breast cancer.

ABSTRACT: There is growing interest in delivering genomically informed cancer therapy. Our aim was to determine the concordance of genomic alterations between primary and recurrent breast cancer. Targeted next-generation sequencing was performed on formalin-fixed paraffin-embedded (FFPE) samples, profiling 3,320 exons of 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer. Point mutations, indels, copy-number alterations (CNA), and select rearrangements were assessed in 74 tumors from 43 patients (36 primary and 38 recurrence/metastases). Alterations potentially targetable with established or investigational therapeutics were considered "actionable." Alterations were detected in 55 genes (mean 3.95 alterations/sample, range 1-12), including mutations in PIK3CA, TP53, ARID1A, PTEN, AKT1, NF1, FBXW7, and FGFR3 and amplifications in MCL1, CCND1, FGFR1, MYC, IGF1R, MDM2, MDM4, AKT3, CDK4, and AKT2. In 33 matched primary and recurrent tumors, 97 of 112 (86.6%) somatic mutations were concordant. Of identified CNAs, 136 of 159 (85.5%) were concordant: 37 (23.3%) were concordant, but below the reporting threshold in one of the matched samples, and 23 (14.5%) discordant. There was an increased frequency of CDK4/MDM2 amplifications in recurrences, as well as gains and losses of other actionable alterations. Forty of 43 (93%) patients had actionable alterations that could inform targeted treatment options. In conclusion, deep genomic profiling of cancer-related genes reveals potentially actionable alterations in most patients with breast cancer. Overall there was high concordance between primary and recurrent tumors. Analysis of recurrent tumors before treatment may provide additional insights, as both gains and losses of targets are observed.

SUBMITTER: Meric-Bernstam F

PROVIDER: S-EPMC4348062 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Concordance of genomic alterations between primary and recurrent breast cancer.

Meric-Bernstam Funda F Frampton Garrett M GM Ferrer-Lozano Jaime J Yelensky Roman R Pérez-Fidalgo Jose A JA Wang Ying Y Palmer Gary A GA Ross Jeffrey S JS Miller Vincent A VA Su Xiaoping X Eroles Pilar P Barrera Juan Antonio JA Burgues Octavio O Lluch Ana M AM Zheng Xiaofeng X Sahin Aysegul A Stephens Philip J PJ Mills Gordon B GB Cronin Maureen T MT Gonzalez-Angulo Ana M AM

Molecular cancer therapeutics 20140307 5

There is growing interest in delivering genomically informed cancer therapy. Our aim was to determine the concordance of genomic alterations between primary and recurrent breast cancer. Targeted next-generation sequencing was performed on formalin-fixed paraffin-embedded (FFPE) samples, profiling 3,320 exons of 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer. Point mutations, indels, copy-number alterations (CNA), and select rearrangements were assessed in 74 tu ...[more]

PMID: 24608573

Similar Datasets

Project description:Metastatic breast cancers have historically been presumed to have the same predictive biomarkers as the initial primary tumor. We compared the expression of these biomarkers in a large paired tissue microarray (TMA) series of primary and subsequent relapsed tumors.Using the British Columbia Cancer Agency Breast Cancer Outcomes Unit database, patients with biopsy-proven relapses were identified and linked to a large TMA series of primary breast cancers from 1986-1992. Charts were reviewed, and tissue blocks of the metastatic cancer were collected to create a separate TMA. Immunohistochemical assessment with the same antibodies and conditions was performed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2 on both the primary and relapsed tumors.One hundred sixty cases were received that had tumor adequate for analyses. Of these, 71.9% had no changes in either the ER or PR status or HER-2 status. Of the 45 (28.1%; 95% confidence interval [CI], 21.2%-35.1%) tumors that did have changes in receptor status, 7.5% were in-breast recurrences or new breast primaries, 4.4% had changes in PR status only and were therefore deemed clinically irrelevant, and 19.4% (95% CI, 13.3%-25.5%) had changes in either the ER or HER-2 status from regional or distant relapses. Five percent of tumors had a receptor status change going from ER(+) or PR(+) to ER(-) or PR(-); 9.4% went from ER(-) or PR(-) to ER(+) or PR(+). With regard to HER-2 status, 3.8% of tumors went from positive to negative and 1.3% went from negative to positive. For all discordant cases, biopsies of the relapsed lesion were obtained prior to initiation of first-line treatment for metastatic disease. In the primary tumors that were ER(+), time to relapse was significantly shorter in the discordant relapsed cases than in the concordant ones (p = .0002). Changes in loss or gain of either biomarker were seen across the discordant cases.A significant proportion of relapsed tumors had changes in either ER or HER-2 status, which would dramatically alter treatment recommendations and clinical behavior. This study suggests that biopsies of relapsed and metastatic breast cancers should be performed routinely in clinical practice.

Dataset Information

Concordance of genomic alterations between primary and recurrent breast cancer.

Publications

Concordance of genomic alterations between primary and recurrent breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets