Prognostic and Predictive Value of IHC4 and ERB1 in the Intergroup Exemestane Study (IES) - On Behalf of the Pathies Investigators

Viale, Giuseppe; Speirs, V.; Bartlett, John M.S.; Mousa, Kelly; Kalaitzaki, E.; Palmieri, Carlo; Reed, Sadie; Bliss, Judith M.; Coombes, R. C.

doi:10.1093/annonc/mdt084.3

Cited by 3 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Across the studies reporting prognostic performance data from unadjusted analyses, none reported survival or recurrence outcomes per risk group. In the validation cohorts, HR analyses showed statistically significant performance when high-risk groups (defined by quartiles or tertiles) were compared with low-risk groups (when reported), whether in LN0/LN+ (n = 4), 24,73,74,77,124,127 LN0-only (n = 3) 58,124,125 or LN+-only (n = 1) 123 patients, and regardless of patient spectrums and treatments received. However, analyses using continuous scores were not always statistically significant or did not report this.…”

Section: Results: Ihc4 Prognostic Performanceunadjusted Analysesmentioning

confidence: 97%

“…(WSG PlanB, 73,74,77 the Kaiser Permanente cohort, 125 IES, 127 the Chinese cohort 58 and the Taiwanese cohort 124 ). Results have not been excluded by IHC4 methodology, as methodologies are not currently standardised and, for this reason, all data are of some relevance.…”

Section: Ihc4 Methodology and Cut-off Points: Ihc4 And Ihc4+c Prognosmentioning

confidence: 99%

Section: Prognostic Performance: Ihc4 and Ihc4+cmentioning

confidence: 99%

“…Eleven separate validation cohorts 24,25,58,73,74,77,[122][123][124][125][126][127][128][129] have reported prognostic performance data for IHC4, with a total of 13,434 patients. 127 and the study from Taiwan. 124 TransATAC, 46 WSG PlanB, 73,74,77 GEICAM 9906, 129 WSG-AGO-Doc, 123 the Kaiser Permanente cohort, 125 the Institut Curie 128 cohort and the Chinese 58 cohort all recruited or reported a subgroup of HER2-patients.…”

Section: Prognostic Performance: Ihc4 and Ihc4+cmentioning

confidence: 99%

See 3 more Smart Citations

Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis

Harnan

Tappenden

Cooper

et al. 2019

Health Technol Assess

View full text Add to dashboard Cite

Background Breast cancer and its treatment can have an impact on health-related quality of life and survival. Tumour profiling tests aim to identify whether or not women need chemotherapy owing to their risk of relapse. Objectives To conduct a systematic review of the effectiveness and cost-effectiveness of the tumour profiling tests oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA), MammaPrint® (Agendia, Inc., Amsterdam, the Netherlands), Prosigna® (NanoString Technologies, Inc., Seattle, WA, USA), EndoPredict® (Myriad Genetics Ltd, London, UK) and immunohistochemistry 4 (IHC4). To develop a health economic model to assess the cost-effectiveness of these tests compared with clinical tools to guide the use of adjuvant chemotherapy in early-stage breast cancer from the perspective of the NHS and Personal Social Services. Design A systematic review and health economic analysis were conducted. Review methods The systematic review was partially an update of a 2013 review. Nine databases were searched in February 2017. The review included studies assessing clinical effectiveness in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I or II cancer with zero to three positive lymph nodes. The economic analysis included a review of existing analyses and the development of a de novo model. Results A total of 153 studies were identified. Only one completed randomised controlled trial (RCT) using a tumour profiling test in clinical practice was identified: Microarray In Node-negative Disease may Avoid ChemoTherapy (MINDACT) for MammaPrint. Other studies suggest that all the tests can provide information on the risk of relapse; however, results were more varied in lymph node-positive (LN+) patients than in lymph node-negative (LN0) patients. There is limited and varying evidence that oncotype DX and MammaPrint can predict benefit from chemotherapy. The net change in the percentage of patients with a chemotherapy recommendation or decision pre/post test ranged from an increase of 1% to a decrease of 23% among UK studies and a decrease of 0% to 64% across European studies. The health economic analysis suggests that the incremental cost-effectiveness ratios for the tests versus current practice are broadly favourable for the following scenarios: (1) oncotype DX, for the LN0 subgroup with a Nottingham Prognostic Index (NPI) of > 3.4 and the one to three positive lymph nodes (LN1–3) subgroup (if a predictive benefit is assumed); (2) IHC4 plus clinical factors (IHC4+C), for all patient subgroups; (3) Prosigna, for the LN0 subgroup with a NPI of > 3.4 and the LN1–3 subgroup; (4) EndoPredict Clinical, for the LN1–3 subgroup only; and (5) MammaPrint, for no subgroups. Limitations There was only one completed RCT using a tumour profiling test in clinical practice. Except for oncotype DX in the LN0 group with a NPI score of > 3.4 (clinical intermediate risk), evidence surrounding pre- and post-test chemotherapy probabilities is subject to considerable uncertainty. There is uncertainty regarding whether or not oncotype DX and MammaPrint are predictive of chemotherapy benefit. The MammaPrint analysis uses a different data source to the other four tests. The Translational substudy of the Arimidex, Tamoxifen, Alone or in Combination (TransATAC) study (used in the economic modelling) has a number of limitations. Conclusions The review suggests that all the tests can provide prognostic information on the risk of relapse; results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence that oncotype DX and MammaPrint are predictive of chemotherapy benefit. Health economic analyses indicate that some tests may have a favourable cost-effectiveness profile for certain patient subgroups; all estimates are subject to uncertainty. More evidence is needed on the prediction of chemotherapy benefit, long-term impacts and changes in UK pre-/post-chemotherapy decisions. Study registration This study is registered as PROSPERO CRD42017059561. Funding The National Institute for Health Research Health Technology Assessment programme.

show abstract

Section: Results: Ihc4 Prognostic Performanceunadjusted Analysesmentioning

confidence: 97%

Section: Ihc4 Methodology and Cut-off Points: Ihc4 And Ihc4+c Prognosmentioning

confidence: 99%

Section: Prognostic Performance: Ihc4 and Ihc4+cmentioning

confidence: 99%

Section: Prognostic Performance: Ihc4 and Ihc4+cmentioning

confidence: 99%

See 2 more Smart Citations

Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis

Harnan

Tappenden

Cooper

et al. 2019

Health Technol Assess

View full text Add to dashboard Cite

show abstract

“…However, estrogen withdrawal therapy using aromatase inhibitors (AI) is now a standard clinical practice in the adjuvant setting for postmenopausal breast cancer, and correlations of response to AIs with (phosphorylated) SRC3 levels need to be assessed within this setting, particularly because the oncogenicity of SRC3 appears modulated by the hormonal milieu in mouse models (42). Currently, the translational arm of the Intergroup Exemestane Study (so-called Path-IES) is exploring the potential role of SRC3 and pS543 in this context (43).…”

Section: Discussionmentioning

confidence: 99%

SRC3 Phosphorylation at Serine 543 Is a Positive Independent Prognostic Factor in ER-Positive Breast Cancer

Zwart

Flach

Abdel-Fatah

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The steroid receptor coactivator SRC3 is essential for the transcriptional activity of estrogen receptor a (ERa). SRC3 is sufficient to cause mammary tumorigenesis, and has also been implicated in endocrine resistance. SRC3 is posttranslationally modified by phosphorylation, but these events have not been investigated with regard to functionality or disease association. Here, we investigate the spatial selectivity of SRC3-pS543/DNA binding over the human genome and its expression in primary human breast cancer in relation with outcome.Experimental Design: Chromatin immunoprecipitation, coupled with sequencing, was used to determine the chromatin binding patterns of SRC3-pS543 in the breast cancer cell line MCF7 and two untreated primary breast cancers. IHC was used to assess the expression of SRC3 and SRC3-pS543 in 1,650 primary breast cancers. The relationship between the expression of SRC3 and SRC3-pS543, disease-free survival (DFS), and breast cancer specific survival (BCSS) was assessed.Results: Although total SRC3 is selectively found at enhancer regions, SRC3-pS543 is recruited to promoters of ERa responsive genes, both in the MCF7 cell line and primary breast tumor specimens. SRC3-pS543 was associated with both improved DFS (P ¼ 0.003) and BCSS (P ¼ 0.001) in tamoxifen untreated highrisk patients, such a correlation was not seen in tamoxifen-treated cases, the interaction was statistically significant (P ¼ 0.001). Multivariate analysis showed SRC3-pS543 to be an independent prognostic factor.Conclusions: Phosphorylation of SRC3 at S543 affects its genomic interactions on a genome-wide level, where SRC3-pS543 is selectively recruited to promoters of ERa-responsive genes. SRC3-pS543 is a prognostic marker, and a predictive marker of response to endocrine therapy. Clin Cancer Res; 22(2); 479-91. Ó2015 AACR.

show abstract

Breast cancer: Current and future endocrine therapies

Palmieri

Patten

Januszewski

et al. 2014

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Prognostic and Predictive Value of IHC4 and ERB1 in the Intergroup Exemestane Study (IES) - On Behalf of the Pathies Investigators

Cited by 3 publications

References 0 publications

Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis

Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis

SRC3 Phosphorylation at Serine 543 Is a Positive Independent Prognostic Factor in ER-Positive Breast Cancer

Breast cancer: Current and future endocrine therapies

Contact Info

Product

Resources

About