Gene-expression assays: New tools to individualize treatment of early-stage breast cancer

Dobbe, Elizabeth; Gurney, Kristen; Kiekow, Sara; Lafferty, Jeffery S.; Kolesar, Jill

doi:10.2146/ajhp060352

Cited by 33 publications

(18 citation statements)

References 11 publications

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“…The gene profiles used to develop CMTC were derived from a commercially available whole-genome microarray platform that has become more affordable than currently available multigene assays, such as MammaPrint (70GS; Agendia Inc, Irvine, CA, USA) and Oncotype DX (Genomic Health, Redwood City, CA, USA), which report only a limited number of genes [24,45] at a high cost [19,50]. Furthermore, the clinical application of CMTC may be extended to other commercial genome-wide microarray platforms, as we have demonstrated the reproducibility of CMTC classification in the validation cohort derived independently from different DNA microarray platforms.…”

Section: Discussionmentioning

confidence: 99%

A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis

et al. 2011

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IntroductionWhen making treatment decisions, oncologists often stratify breast cancer (BC) into a low-risk group (low-grade estrogen receptor-positive (ER+)), an intermediate-risk group (high-grade ER+) and a high-risk group that includes Her2+ and triple-negative (TN) tumors (ER-/PR-/Her2-). None of the currently available gene signatures correlates to this clinical classification. In this study, we aimed to develop a test that is practical for oncologists and offers both molecular characterization of BC and improved prediction of prognosis and treatment response.MethodsWe investigated the molecular basis of such clinical practice by grouping Her2+ and TN BC together during clustering analyses of the genome-wide gene expression profiles of our training cohort, mostly derived from fine-needle aspiration biopsies (FNABs) of 149 consecutive evaluable BC. The analyses consistently divided these tumors into a three-cluster pattern, similarly to clinical risk stratification groups, that was reproducible in published microarray databases (n = 2,487) annotated with clinical outcomes. The clinicopathological parameters of each of these three molecular groups were also similar to clinical classification.ResultsThe low-risk group had good outcomes and benefited from endocrine therapy. Both the intermediate- and high-risk groups had poor outcomes, and their BC was resistant to endocrine therapy. The latter group demonstrated the highest rate of complete pathological response to neoadjuvant chemotherapy; the highest activities in Myc, E2F1, Ras, β-catenin and IFN-γ pathways; and poor prognosis predicted by 14 independent prognostic signatures. On the basis of multivariate analysis, we found that this new gene signature, termed the "ClinicoMolecular Triad Classification" (CMTC), predicted recurrence and treatment response better than all pathological parameters and other prognostic signatures.ConclusionsCMTC correlates well with current clinical classifications of BC and has the potential to be easily integrated into routine clinical practice. Using FNABs, CMTC can be determined at the time of diagnostic needle biopsies for tumors of all sizes. On the basis of using public databases as the validation cohort in our analyses, CMTC appeared to enable accurate treatment guidance, could be made available in preoperative settings and was applicable to all BC types independently of tumor size and receptor and nodal status. The unique oncogenic signaling pathway pattern of each CMTC group may provide guidance in the development of new treatment strategies. Further validation of CMTC requires prospective, randomized, controlled trials.

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Section: Discussionmentioning

confidence: 99%

A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis

et al. 2011

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“…The development in oncogene profiling in the last decade has slowly been established as clinical tools. For example, Oncotype DXÒ on the basis of 21 genes has been shown to predict 10-year distant recurrence in patients with estrogen receptor-positive, axillary lymph node-negative breast cancer [10,11]. The wide spread use of these tools is expected to provide additional prognostic predictors other than the traditional tumor staging and node status to determine the optimal management for each patient.…”

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confidence: 99%

Can dynamic contrast-enhanced MRI (DCE-MRI) predict tumor recurrence and lymph node status in patients with breast cancer?

Bahri

Chen

et al. 2008

Annals of Oncology

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The lymph node status is regarded as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. While morphological features and contrast enhancement kinetics of breast cancer shown on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been correlated with tumor histological type, grade, and biomarkers [1][2][3][4], there were only few studies reporting the association of lesion features such as rim enhancement and kinetic feature (early maximal enhancement and washout) with node status and showed controversial results [5][6][7]. In this study, we investigated the MRI features of the primary tumor between patients who had early recurrence versus those who remained cancer free and also between node-positive and -negative patients.We analyzed 62 patients (30-83 years old, median 58) with histologically confirmed breast cancer who were enrolled into a breast MRI study during years [2000][2001][2002][2003]. A telephone survey was conducted in 2006 to follow-up all patients regarding their disease status. Of the 62 patients, six had confirmed cancer recurrence in the previously treated breast. The MRI features of these 62 patients were retrospectively reviewed and compared between the six with early recurrence versus those who were cancer free. Of these six patients with early recurrence, three had positive nodes (sentinel and/or axillary) at the time of first cancer diagnosis and three had negative nodes. Of the 56 patients who were cancer free, 28 had positive node and the other 28 had negative nodes.Breast MRI was carried out on a 1.5T MR scanner. The protocol included precontrast images and dynamic contrastenhanced imaging. The characteristics of primary tumor were analyzed. The longest and perpendicular dimension of the tumor size was measured on contrast-enhanced MRI and then converted to one-dimensional size. The morphological appearances were characterized using features described in BI-RADS MRI lexicon [8], separated into mass lesions and nonmass-like enhancements. The following enhancement kinetic parameters were analyzed: the % enhancement at 1 min (E1), 2 min (E2), 7 min (E3), and the washout slope between 7 and 2 min. Furthermore, pharmacokinetic parameters, including transfer constant (K trans ) and exchange rate constant (k ep ), were also analyzed with the Toft's twocompartmental model [9].The comparison of lesion morphology, size, and enhancement kinetic parameters in three groups was summarized in Table 1. LN(+) group had more irregular mass lesion (19/28, 68%) compared with LN(2) group (12/28, 43%), fewer round mass (4/28, 14% versus 10/28, 36%), and more nonmass-like lesions (3/28 versus 0/28). The tumor size in the LN(+) group (0.7-4.0 cm, mean 1.8 cm) was bigger letters to the editor Annals of Oncology 822 | letters to the editor Volume

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“…Several novel prognostic indices of breast cancer were reported [2,20,49,56]. Miller et al [49] reported that the expression patterns of 84 elements, which were extracted from 23,343 unique genetic elements of cDNA microarrays from 26 tumors, had the potential to distinguish high and low Nottingham Prognostic Index patient samples.…”

Section: Discussionmentioning

confidence: 99%

“…Dobbe et al reviewed two gene expression assays and concluded that the two gene expression assays, Oncotype DX and MammaPrint, have been developed to determine the risk of breast cancer recurrence in patients with stage I or II node-negative breast cancer. In the future, these tests may be useful in determining the need for systemic adjuvant therapy in such patients [20]. Asaka et al [2] constructed a novel genetic prognostic index among node-positive breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Prediction of outcome of patients with metastatic breast cancer: evaluation with prognostic factors and Nottingham prognostic index

Liu

Huang

Wang

et al. 2009

Support Care Cancer

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Gene-expression assays: New tools to individualize treatment of early-stage breast cancer

Cited by 33 publications

References 11 publications

A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis

A new gene expression signature, the ClinicoMolecular Triad Classification, may improve prediction and prognostication of breast cancer at the time of diagnosis

Can dynamic contrast-enhanced MRI (DCE-MRI) predict tumor recurrence and lymph node status in patients with breast cancer?

Prediction of outcome of patients with metastatic breast cancer: evaluation with prognostic factors and Nottingham prognostic index

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