Time filter

Source Type

Ades F.,University of Waterloo | Senterre C.,Free University of Colombia | Zardavas D.,Breast International Group Headquarters BIG aisbl | De Azambuja E.,University of Waterloo | And 3 more authors.
European Journal of Cancer | Year: 2014

Background The European Union (EU) has adopted a common procedure for granting marketing authorisation for cancer drugs. Nevertheless, pricing and reimbursement decisions are a competency of EU national governments, and their policies are diverse. We aimed to evaluate the time for trastuzumab reimbursement approval and its association to health expenditure, to health policy performance, to the availability of cost-effectiveness studies and to breast cancer outcome. Methods Breast cancer outcome was estimated by the mortality/incidence (M/I) ratio. Trastuzumab reimbursement approval dates were provided by Roche. Spearman's rank correlation and Wilcoxon rank-sum test were used to evaluate associations and/or differences between the variables studied. Additional analyses were made by grouping countries according to compliance to the 180 day timeframe stipulated in the EU 89/105/EEC Directive for drug pricing and reimbursement. Results A statistically significant inverse and strong correlation between breast cancer M/I ratio and health expenditure (rs = -0.730, p < 0.001) and health policy performance (rs = -0.711, p < 0.001) was found, meaning the better the score and the higher the expenditure, the fewer patients died after a breast cancer diagnosis. Factors associated with trastuzumab faster reimbursement and compliance to the 89/105/EEC Directive were better health policy score, higher health expenditure and availability of cost-effectiveness studies. Conclusion Higher health policy scores and health expenditure are associated with faster reimbursement of trastuzumab and better breast cancer outcome. Although the study design does not allow inference of causal associations, a marked difference is observed between Eastern and Western Europe, with long delays and increased breast cancer mortality identified in Eastern European countries. © 2014 Elsevier Ltd. All rights reserved.

Desmedt C.,University of Waterloo | Fumagalli D.,University of Waterloo | Pietri E.,Istituto Scientifico Romagnolo per Lo Studio e la Cura Dei Tumouri | Zoppoli G.,University of Waterloo | And 28 more authors.
Journal of Pathology | Year: 2015

Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non-silent coding mutations in 360 protein-coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as 'oncogenic' in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole-genome rearrangement screen was further conducted in 8/36 patients. Twenty-four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three-quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter-lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome-wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter-lesion heterogeneity in one-third, despite similar pathological features. This implies that deeper molecular characterization of all MFBC lesions is warranted for the adequate management of those cancers. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2015 The Authors.

Tryfonidis K.,European Organization for Research and Treatment of Cancer EORTC Headquarters | Zardavas D.,Breast International Group Headquarters BIG aisbl | Cardoso F.,Breast Unit
Cancer Treatment Reviews | Year: 2014

Small (T1a, b), lymph node negative breast tumors represent an entity diagnosed with increasing frequency due to the implementation of wide-scale screening programs. Patients bearing such tumors usually exhibit favorable long-term outcomes, with low breast cancer mortality rates at 10. years, even in the absence of adjuvant chemotherapy. However, most available data derive from retrospective studies. Additionally, a subset of patients with these tumors experience recurrence of the disease, indicating that early tumor stage itself is not a sufficient prognosticator. It is of paramount importance to refine the prognosis of this population, identifying patients with high risk of recurrence, for whom adjuvant treatment is needed. The underlying biology of the disease provides relevant information, such as grade and status of hormone receptors and HER-2 (human epidermal growth factor receptor 2), with high grade, triple negative and HER-2-positive tumors having worse prognosis. Additionally, multigene signatures may improve further the prognostication of patients with small, node negative breast cancers. Further research for this increasingly frequent group of patients is urgently needed, so that better informed clinical decision making, in particular regarding adjuvant chemotherapy, can occur. © 2014 Elsevier Ltd.

Zardavas D.,Breast International Group Headquarters BIG aisbl | Zardavas D.,Free University of Colombia | Maetens M.,Breast International Group Headquarters BIG aisbl | Maetens M.,Free University of Colombia | And 23 more authors.
British Journal of Cancer | Year: 2014

Metastatic breast cancer is one of the leading causes of cancer-related mortality among women in the Western world. To date most research efforts have focused on the molecular analysis of the primary tumour to dissect the genotypes of the disease. However, accumulating evidence supports a molecular evolution of breast cancer during its life cycle, with metastatic lesions acquiring new molecular aberrations. Recognising this critical gap of knowledge, the Breast International Group is launching AURORA, a large, multinational, collaborative metastatic breast cancer molecular screening programme. Approximately 1300 patients with metastatic breast cancer who have received no more than one line of systemic treatment for advanced disease will, after giving informed consent, donate archived primary tumour tissue, as well as will donate tissue collected prospectively from the biopsy of metastatic lesions and blood. Both tumour tissue types, together with a blood sample, will then be subjected to next generation sequencing for a panel of cancer-related genes. The patients will be treated at the discretion of their treating physicians per standard local practice, and they will be followed for clinical outcome for 10 years. Alternatively, depending on the molecular profiles found, patients will be directed to innovative clinical trials assessing molecularly targeted agents. Samples of outlier patients considered as 'exceptional responders' or as 'rapid progressors' based on the clinical follow-up will be subjected to deeper molecular characterisation in order to identify new prognostic and predictive biomarkers. AURORA, through its innovative design, will shed light onto some of the unknown areas of metastatic breast cancer, helping to improve the clinical outcome of breast cancer patients. © 2014 Cancer Research UK.

Zardavas D.,Breast International Group Headquarters BIG aisbl | Zardavas D.,Free University of Colombia | Piccart M.,Breast International Group Headquarters BIG aisbl | Piccart M.,Free University of Colombia
Annual Review of Medicine | Year: 2015

Neoadjuvant treatment of breast cancer refers to the use of different treatment modalities prior to surgical excision of the tumor. It has been accepted as a treatment option for patients with nonmetastatic disease, because it renders inoperable tumors operable and increases the rates of breast-conserving surgery, while achieving similar long-term clinical outcomes as adjuvant treatment. The neoadjuvant setting is being increasingly perceived as a research platform, where the biologic effects of traditional anticancer agents can be delineated, prognostic and predictive biomarkers can be identified, and the development of targeted agents can be expedited. Surrogate endpoints that can predict long-term clinical outcome and are evaluable early on, such as the pathologic complete response, offer valuable opportunities for rapid assessment of anticancer agents. Additionally, efforts for molecular profiling of the post-neoadjuvant residual disease hold the potential to lead to personalized therapy for breast cancer patients with early-stage high-risk disease. © 2015 by Annual Reviews.

Discover hidden collaborations