"Prediction of risk of recurrence is an open issue in clinical management of early breast cancer. Much effort has been made to develop gene-based predictors, and some have been challenged for their clinical utility (Sparano, 2006; Cardoso et al, 2007). More recently, a new class of small RNAs, miRNAs, has been suggested to have a key role in breast cancer and to be able to give prognostic information (Foekens et al, 2008; Rothe et al, 2011; Falkenberg et al, 2013). "
[Show abstract][Hide abstract] ABSTRACT: Breast cancer clinical outcome is affected by tumor molecular features, and the identification of subtype-specific prognostic biomarkers is relevant for breast cancer translational research. Gene expression signatures proved to be able to complement prognostic information provided by classical clinico-pathological features. Recently, microRNAs (miRNAs) have been causally linked to tumorigenesis and cancer progression and have been associated with patient outcome, also in breast cancer.
MicroRNAs associated with the development of distant metastasis were identified in a cohort of 92 ESR1+/ERBB2- lymph node-negative breast cancers from patients not receiving adjuvant treatment. Results were confirmed and further investigated in a total of 1246 miRNA and gene expression profiles of the Molecular Taxonomy of Breast Cancer International Consortium data set. Moderated t-test, univariable and multivariable Cox regression models were used for statistical analyses.
miR-30e* was identified as independent protective prognostic factor in lymph node-negative untreated patients with ESR1+/ERBB2- tumours and retained a significant association with a good prognosis in treated patients with the same tumor subtype as well as in the ERBB2+ subtype, but not in ESR1-/ERBB2- tumours.
We highlighted a relevant and subtype-specific role in breast cancer for miR-30e* and demonstrated that adding miRNA markers to gene signatures and clinico-pathological features can help for a better prognostication.British Journal of Cancer advance online publication, 9 June 2015; doi:10.1038/bjc.2015.206 www.bjcancer.com.
British Journal of Cancer 06/2015; 113(2). DOI:10.1038/bjc.2015.206 · 4.84 Impact Factor
"Of patients with a low-risk score, 16 received chemotherapy (n = 16, 14%). All 16 patients were enrolled to the TAILORx trial, and had a recurrence score in excess of 11, and were randomised to chemotherapy as per protocol . Sixty-five (65%) of patients deemed to be of intermediate recurrence risk were prescribed adjuvant chemotherapy . "
[Show abstract][Hide abstract] ABSTRACT: Abstract
The use of chemotherapy in node-negative, (O)Estrogen Receptor (ER)-positive breast cancer has changed significantly since the introduction of Oncotype DX to determine systemic recurrence risk based on tumour genomic signature.
This study aims to:
1.Document longitudinal changes in chemotherapy use,
2.Assess the impact of new evidence on local protocol.
A cohort study was undertaken, including consecutive patients with early node-negative, ER-positive breast cancer diagnosed between 2006 and May 2013, including a period of prospective clinical trial (Trial Assigning Individualised Options for Treatment (TAILORx)) recruitment. Data were collected regarding patient demographics, tumour clinico-pathological features, Oncotype DX use and recurrence score and chemotherapy use. All therapeutic decisions were made following multidisciplinary discussion, with adherence to guidelines and consideration of trial protocol and Oncotype DX recurrence scores.
479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial. Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling. From October 2011, Oncotype DX was used in all eligible patients as per National Cancer Control Programme (NCCP) guidelines. A total of 216 (45%) patients received chemotherapy. The use of chemotherapy changed in inverse proportion to the availability of the genomic assay. Of those patients in whom Oncotype DX was utilised, 138 (57%) were spared chemotherapy.
This study validates the use of molecular testing in the rationalisation of systemic therapy.
European Journal of Cancer 09/2014; 50(16). DOI:10.1016/j.ejca.2014.08.002 · 5.42 Impact Factor
"In contrast to our data, BCL2 positivity in the mentioned study continued to be associated with a favorable prognostic effect throughout the whole follow-up period of 8.4 years. Of note, BCL2 is part of the 21-gene signatures (Oncotype DX Ò Genomic Health), though BCL2 protein expression and transcriptional levels are not perfectly correlated  . "
[Show abstract][Hide abstract] ABSTRACT: Given recent data on genetic heterogeneity within and individual's tumor, we investigated if there were differences in the prognostic and predictive abilities of BCL2 and TP53 protein expression in primary breast cancer (TU) and corresponding axillary lymph-nodes (LN). We used patient samples from the adjuvant Belgian three-arm study which randomized between anthracycline containing regimens and traditional CMF. The endpoints analyzed were overall survival (OS), event-free survival (EFS) and interactions between chemotherapy regimens. At a median follow-up of 15.6 years, BCL2 and TP53 (in both TU and LN) were significantly associated with OS but only in the first 5 years. Likewise, BCL2 and TP53 (in both TU and LN) were associated with EFS in the first 2 years after randomization, with no association after 2 years. BCL2 and TP53 remained statistically significant after adjustment for the standard clinical-pathological characteristics in regard to OS and EFS in the respective first years after randomization, (p value < 0.001 for both markers). Furthermore, an interaction was found between high BCL2 expression in the TU (but not in LN) and benefit to CMF over anthracycline-based chemotherapy (interaction p value EFS: 0.042; OS = 0.01). No interaction was found for TP53 expression neither in TU nor in LN. We conclude that BCL2 and TP53 were predictive biomarkers for better and worse survival respectively, but only in the first two to five years after diagnosis. BCL2 expression in the TU but not in the LN was predictive of increased benefit to CMF vs anthracycline-based chemotherapy.
Breast (Edinburgh, Scotland) 04/2014; 23(4). DOI:10.1016/j.breast.2014.03.012 · 2.38 Impact Factor
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