John M S Bartlett

Ontario Institute for Cancer Research, Toronto, Ontario, Canada

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Publications (231)1251.31 Total impact

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    ABSTRACT: Evidence supporting the clinical utility of predictive biomarkers of anthracycline activity is weak, with a recent meta-analysis failing to provide strong evidence for either HER2 or TOP2A. Having previously shown that duplication of chromosome 17 pericentromeric alpha satellite as measured with a centromere enumeration probe (CEP17) predicted sensitivity to anthracyclines, we report here an individual patient-level pooled analysis of data from five trials comparing anthracycline-based chemotherapy with CMF (cyclophosphamide, methotrexate, and fluorouracil) as adjuvant chemotherapy for early breast cancer. Fluorescent in situ hybridization for CEP17, HER2, and TOP2A was performed in three laboratories on samples from 3,846 of 4,864 eligible patients from five trials evaluating anthracycline-containing chemotherapy versus CMF. Methodologic differences did not affect HER2-to-CEP17 ratios but necessitated different definitions for CEP17 duplication: > 1.86 observed copies per cell for BR9601, NEAT, Belgian, and DBCG89D trials and > 2.25 for the MA.5 trial. Fluorescent in situ hybridization data were available in 89.3% (HER2), 83.9% (CEP17), and 80.6% (TOP2A) of 3,846 patient cases with available tissue. Both CEP17and TOP2A treatment-by-marker interactions remained significant in adjusted analyses for recurrence-free and overall survival, whereas HER2 did not. A combined CEP17 and TOP2A-adjusted model predicted anthracycline benefit across all five trials for both recurrence-free (hazard ratio, 0.64; 95% CI, 0.51 to 0.82; P = .001) and overall survival (hazard ratio, 0.66; 95% CI, 0.51 to 0.85; P = .005). This prospectively planned individual-patient pooled analysis of patient cases from five adjuvant trials confirms that patients whose tumors harbor either CEP17 duplication or TOP2A aberrations, but not HER2 amplification, benefit from adjuvant anthracycline chemotherapy. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 05/2015; 33. DOI:10.1200/JCO.2013.54.7869 · 17.88 Impact Factor
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    ABSTRACT: FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14-1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.
    Oncotarget 04/2015; · 6.63 Impact Factor
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    ABSTRACT: Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.Modern Pathology advance online publication, 20 February 2015; doi:10.1038/modpathol.2015.38.
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    ABSTRACT: Evidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with different endocrine treatment regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant hormonal treatment, randomly assigned to different regimens: 5 years of exemestane or sequential treatment (2.5 years of tamoxifen-2.5 years of exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G, and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune susceptible) were determined by the effect size of mono-immune markers on relapse rate. Patients on sequential treatment with high level of tumor-infiltrating FoxP3+ cells had significant (p = 0.019, HR 0.729, 95 % CI 0.560-0.949) better OS. Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS p < 0.001). Tumor IS were only of prognostic value for the sequentially endocrine-treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95 % CI 0.878-2.297; HR low IS 1.657, 95 % CI 1.131-2.428; BCSS: p = 0.002, HR intermediate IS 2.486, 95 % CI 1.375-4.495; HR low IS 2.422, 95 % CI 1.439-4.076; and OS: p = 0.005, HR intermediate IS 1.509, 95 % CI 0.950-2.395; HR low IS 1.848, 95 % CI 1.277-2.675). Tregs and the tumor IS presented in this study harbor prognostic value for sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for solely exemestane-treated patients. Therefore, these markers could be used as a clinical risk stratification tool to guide adjuvant treatment in this BC population.
    Breast Cancer Research and Treatment 02/2015; 149(3):587-596. DOI:10.1007/s10549-015-3269-7 · 4.20 Impact Factor
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    ABSTRACT: Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies in patients with HER2-positive breast cancer have emphasised the need for accurate assessment of HER2 status. Current data indicate that HER2 test accuracy improved following previous publication of guidelines and the implementation of an external quality assessment scheme with a decline in false-positive and false-negative rates. This paper provides an update of the guidelines for HER2 testing in the UK. The aim is to further improve the analytical validity and clinical utility of HER2 testing by providing guidelines of test performance parameters, and recommendations on the postanalytical interpretation of test results. HER2 status should be determined in all newly diagnosed and recurrent breast cancers. Testing involves immunohistochemistry with >10% complete strong membrane staining defining a positive status. In situ hybridisation, either fluorescent or bright field chromogenic, is used either upfront or in immunohistochemistry borderline cases to detect the presence of HER2 gene amplification. Situations where repeat HER2 testing is advised are outlined and the impact of genetic heterogeneity is discussed. Strict quality control and external quality assurance of validated assays are essential. Testing laboratories should perform ongoing competency assessment and proficiency tests and ensure the reliability and accuracy of the assay. Pathologists, oncologists and surgeons involved in test interpretation and clinical use should adhere to published guidelines and maintain accurate performance and consistent interpretation of test results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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    ABSTRACT: The pre-eminent goal of biobanks is to accelerate scientific discovery and support improvements in healthcare through the supply of high quality biospecimens to enable excellent science. Despite the need for retrospective future-proofed cancer repositories, they are presented with significant fiscal challenges. While it was once thought that biobanks could recover most, if not all, operational costs through distribution fees, biobanks have been consistently unable to fully realize this dream. Using data from three mature Canadian cancer biobanks, common attributes and assumptions related to cost recovery were evaluated. The values were entered into a simple financial model to determine the cost recovery potential for biobanks. Over a 5-year period analyzed, aliquots from almost 40% (8990) of 23055 cases collected have been distributed in whole or in part to researchers. The financial modeling demonstrates that, based on values derived from the real life experiences of three major Canadian biobanks, full cost recovery through distribution is not feasible. A more realistic, experience based, expectation of cost recovery from distribution fees is in the range of 5%-25%, and this range is lower if only academic research is supported as opposed to also supporting industry researchers. Biobanks are expensive and, to mitigate costs, are frequently challenged to operate under "self-sustainable" financial models. However, the only possible route to self-sustainability through distribution fees in today's market would require an almost exclusive targeting of commercial researchers and, even then, evidence suggests this is an impossible goal to attain. Support for biobanks should recognize that they exist to further development of personalized treatments and diagnostics essential for precision medicine. For biobanks to continue to achieve this goal, pro bono publicum, funders need to be aware of the full funding requirements of biobanks and create appropriate funding streams.
    Biopreservation and Biobanking 12/2014; 12(6):374-80. DOI:10.1089/bio.2014.0051 · 1.58 Impact Factor
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    ABSTRACT: Background:We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial.Methods:The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years.Results:We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P<0.05), with increases in R(2) between 5 and 6% and increases in D-statistic between 0.16 and 0.21.Conclusions:Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy.British Journal of Cancer advance online publication, 14 October 2014; doi:10.1038/bjc.2014.530 www.bjcancer.com.
    British Journal of Cancer 10/2014; 111(12). DOI:10.1038/bjc.2014.530 · 4.82 Impact Factor
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    ABSTRACT: The question of how best to attribute the unit costs of the annotated biospecimen product that is provided to a research user is a common issue for many biobanks. Some of the factors influencing user fees are capital and operating costs, internal and external demand and market competition, and moral standards that dictate that fees must have an ethical basis. It is therefore important to establish a transparent and accurate costing tool that can be utilized by biobanks and aid them in establishing biospecimen user fees. To address this issue, we built a biospecimen user fee calculator tool, accessible online at www.biobanking.org . The tool was built to allow input of: i) annual operating and capital costs; ii) costs categorized by the major core biobanking operations; iii) specimen products requested by a biobank user; and iv) services provided by the biobank beyond core operations (e.g., histology, tissue micro-array); as well as v) several user defined variables to allow the calculator to be adapted to different biobank operational designs. To establish default values for variables within the calculator, we first surveyed the members of the Canadian Tumour Repository Network (CTRNet) management committee. We then enrolled four different participants from CTRNet biobanks to test the hypothesis that the calculator tool could change approaches to user fees. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated significant variation in estimated pricing that was reduced by calculated pricing, and that higher user fees are consistently derived when using the calculator. We conclude that adoption of this online calculator for user fee determination is an important first step towards harmonization and realistic user fees.
    Biopreservation and Biobanking 08/2014; 12(4):234-239. DOI:10.1089/bio.2014.0008 · 1.58 Impact Factor
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    ABSTRACT: Deregulation of key PI3K/AKT pathway genes may contribute to endocrine resistance in breast cancer (BC). PIK3CA is the most frequently mutated gene in luminal BC (35%); however, the effect of mutations in helical versus kinase domains remains controversial. We hypothesize that improved outcomes occur in patients with estrogen receptor–positive (ER positive) BC receiving endocrine therapy and possessing PIK3CA mutations. DNA was extracted from 4,540 formalin-fixed paraffin-embedded BC samples from the Exemestane Versus Tamoxifen-Exemestane pathology study. Mutational analyses were performed for 25 mutations (PIK3CAx10, AKT1x1, KRASx5, HRASx3, NRASx2 and BRAFx4). PIK3CA mutations were frequent (39.8%), whereas RAS/RAF mutations were rare (1%). In univariable analyses PIK3CA mutations were associated with significantly improved 5-year distant relapse-free survival (DRFS; HR, 0.76; 95% CI, 0.63 to 0.91; P = .003). However, a multivariable analysis correcting for known clinical and biologic prognostic factors failed to demonstrate that PIK3CA mutation status is an independent prognostic marker for DRFS (HR, 0.92; 95% CI, 0.75 to 1.12; P = .4012). PIK3CA mutations were more frequent in low-risk luminal BCs (e.g., grade 1 nodev 3, node-negative v -positive), confounding the relationship between mutations and outcome. PIK3CA mutations are present in approximately 40% of luminal BCs but are not an independent predictor of outcome in the context of endocrine therapy, whereas RAS/RAF mutations are rare inluminal BC. A complex relationship between low-risk cancers and PIK3CA mutations was identified. Although the PI3K/AKT pathway remains a viable therapeutic target as the result of ahigh mutation frequency, PIK3CA mutations do not seem to affect residual risk following treatment with endocrine therapy.
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    ABSTRACT: T-cell infiltration in estrogen receptor (ER)-negative breast tumours has been associated with longer survival. To investigate this association and the potential of tumour T-cell infiltration as a prognostic and predictive marker, we have conducted the largest study of T cells in breast cancer to date.
    Annals of Oncology 06/2014; 25(8). DOI:10.1093/annonc/mdu191 · 6.58 Impact Factor
  • Cancer Research 03/2014; 73(24 Supplement):P5-08-14-P5-08-14. DOI:10.1158/0008-5472.SABCS13-P5-08-14 · 9.28 Impact Factor
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    ABSTRACT: The TACT trial is the largest study assessing the benefit of taxanes as part of adjuvant therapy for early breast cancer. The goal of this translational study was to clarify the predictive and prognostic value of Tau within the TACT trial. Tissue microarrays (TMA) were available from 3,610 patients. ER, PR, HER2 from the TACT trial and Tau protein expression was determined by immunohistochemistry on duplicate TMAs. Two parallel scoring systems were generated for Tau expression ('dichotomised' vs. 'combined' score). The positivity rate of Tau expression was 50 % in the trial population (n = 2,483). Tau expression correlated positively with ER (p < 0.001) and PR status (p < 0.001); but negatively with histological grade (p < 0.001) and HER2 status (p < 0.001). Analyses with either scoring systems for Tau expression demonstrated no significant interaction between Tau expression and efficacy of docetaxel. Contrary to the hypothesis that taxane benefit would be enriched in Tau negative/low patients, the only groups with a suggestion of a reduced event rate in the taxane group were the HER2-positive, Tau positive subgroups. Tau expression was seen to be a prognostic factor on univariate analysis associated with an improved DFS, independent of the treatment group (p < 0.001). It had no prognostic value in ER-negative tumours and the weak prognostic effect of Tau in ER-positive tumours (p = 0.02) diminished, when considering ER as an ordinal variable. On multivariable analyses, Tau had no prognostic value in either group. In addition, no significant interaction between Tau expression and benefit from docetaxel in patients within the PR-positive and negative subsets was seen. This is now the second large adjuvant study, and the first with quantitative analysis of ER and Tau expression, failing to show an association between Tau and taxane benefit with limited utility as a prognostic marker for Tau in ER-positive early breast cancer patients.
    Breast Cancer Research and Treatment 02/2014; DOI:10.1007/s10549-014-2855-4 · 4.20 Impact Factor
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    ABSTRACT: Each year funding agencies and academic institutions spend millions of dollars and euros on biobanking. All funding providers assume that after initial investments biobanks should be able to operate sustainably. However the topic of sustainability is challenging for the discipline of biobanking for several major reasons: the diversity in the biobanking landscape, the different purposes of biobanks, the fact that biobanks are dissimilar to other research infrastructures and the absence of universally understood or applicable value metrics for funders and other stakeholders. In this article our aim is to delineate a framework to allow more effective discussion and action around approaches for improving biobank sustainability. The term sustainability is often used to mean fiscally self-sustaining, but this restricted definition is not sufficient for biobanking. Instead we propose that biobank sustainability should be considered within a framework of three dimensions - financial, operational, and social. In each dimension, areas of focus or elements are identified that may allow different types of biobanks to distinguish and evaluate the relevance, likelihood, and impact of each element, as well as the risks to the biobank of failure to address them. Examples of practical solutions, tools and strategies to address biobank sustainability are also discussed.
    Biopreservation and Biobanking 02/2014; 12(1):60-8. DOI:10.1089/bio.2013.0064 · 1.58 Impact Factor
  • John M S Bartlett, Kathleen I Pritchard, Melanie Spears
    CancerSpectrum Knowledge Environment 01/2014; 106(1):djt360. DOI:10.1093/jnci/djt360 · 15.16 Impact Factor
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    San Antonio Breast Cancer Symposium 2013, San Antonio, Texas; 12/2013
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    ABSTRACT: Tissue MicroArrays (TMAs) are effective tool for performing high-throughput standardization analyses of biomarkers; but evidence implicating core number required to be representative of whole tumor is lacking. Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. The number and size of cores that can best represent DCIS lesion is unknown. Rather than performing extensive experiments using several variants of physical TMAs, we have developed a "virtual TMA" approach which is effective at optimizing biomarker discovery and validation. Whole DCIS sections from 95 patients were evaluated by IHC for ER, PgR, HER2 and Ki-67. Histoscores were generated manually for ER, PgR and HER2 as well as% positivity for Ki-67. Slides were scanned using the FDA-approved Ariol SL50 Image Analysis system and utilized the V Array (Virtual Array) module. Virtual cores created virtual TMAs, and applied to our validated scoring classifiers. Automated histoscores and% positivity were determined, and compared against increasing numbers of cores. The number of optimal cores was based on concordant results between virtual TMAs and corresponding whole sections. We have shown that V Arrays is an important tool in digital pathology in both research and clinical settings. This article is protected by copyright. All rights reserved.
    Histopathology 11/2013; 65(1). DOI:10.1111/his.12336 · 3.30 Impact Factor
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    ABSTRACT: Screening for invasive cancer has led to a marked increase in the detection of ductal carcinoma in situ (DCIS). DCIS is, if appropriately managed, a low-risk disease which has a small chance of impacting on patient life expectancy. However, despite significant advances in prognostic marker development in invasive breast cancer, there are no validated diagnostic assays to inform treatment choice for women with DCIS. Therefore we are unable to target effective treatment strategies to women at high risk and avoid over-treatment of women at low risk of progression to invasive breast cancer. Paradoxically, one effect of this uncertainty is undertreatment of some women.Content:We review current practice and research in the field to identify key challenges in the management of DCIS. The impact of clinical research, particularly on the over and undertreatment of women with DCIS is assessed. We note slow progress toward development of diagnostic biomarkers and highlight key opportunities to accelerate advances in this area.Summary:DCIS is a low-risk disease, its incidence is increasing, and current treatment is effective. However, many women are either over- or undertreated. Despite repeated calls for development of diagnostic biomarkers, progress in this area has been slow, reflecting a relative lack of investment of research effort and funding. Given the low event rate in treated patients and the lateness of recurrences, many previous studies have only limited power to identify independent prognostic and predictive biomarkers. However, the potential for such biomarkers to personalize treatment for DCIS is extremely high.
    Clinical Chemistry 11/2013; 60(1). DOI:10.1373/clinchem.2013.207183 · 7.77 Impact Factor
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    ABSTRACT: In breast cancer, immunohistochemical assessment of proliferation using the marker Ki67 has potential use in both research and clinical management. However, lack of consistency across laboratories has limited Ki67's value. A working group was assembled to devise a strategy to harmonize Ki67 analysis and increase scoring concordance. Toward that goal, we conducted a Ki67 reproducibility study. Eight laboratories received 100 breast cancer cases arranged into 1-mm core tissue microarrays-one set stained by the participating laboratory and one set stained by the central laboratory, both using antibody MIB-1. Each laboratory scored Ki67 as percentage of positively stained invasive tumor cells using its own method. Six laboratories repeated scoring of 50 locally stained cases on 3 different days. Sources of variation were analyzed using random effects models with log2-transformed measurements. Reproducibility was quantified by intraclass correlation coefficient (ICC), and the approximate two-sided 95% confidence intervals (CIs) for the true intraclass correlation coefficients in these experiments were provided. Intralaboratory reproducibility was high (ICC = 0.94; 95% CI = 0.93 to 0.97). Interlaboratory reproducibility was only moderate (central staining: ICC = 0.71, 95% CI = 0.47 to 0.78; local staining: ICC = 0.59, 95% CI = 0.37 to 0.68). Geometric mean of Ki67 values for each laboratory across the 100 cases ranged 7.1% to 23.9% with central staining and 6.1% to 30.1% with local staining. Factors contributing to interlaboratory discordance included tumor region selection, counting method, and subjective assessment of staining positivity. Formal counting methods gave more consistent results than visual estimation. Substantial variability in Ki67 scoring was observed among some of the world's most experienced laboratories. Ki67 values and cutoffs for clinical decision-making cannot be transferred between laboratories without standardizing scoring methodology because analytical validity is limited.
    CancerSpectrum Knowledge Environment 11/2013; 105(24). DOI:10.1093/jnci/djt306 · 15.16 Impact Factor
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    ABSTRACT: Background: Epidermal growth factor receptors contribute to breast cancer relapse during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve outcomes in HER-positive cancers. Methods: Tissue microarrays were constructed. Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed relative to disease-free survival and treatment using outcomes at 2.75 and 6.5 years. Results: Among 4541 eligible samples, 4225 (93%) had complete HER1–3 data. Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32% (n=1351) overexpressed at least one HER receptor. In the HER1–3-negative subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years was 0.67 (95% confidence interval (CI), 0.52–0.87), in the HER1–3-positive subgroup, the HR was 1.15 (95% CI, 0.85–1.56). A prospectively planned treatment-by-marker analysis demonstrated a significant interaction between HER1–3 and treatment at 2.75 years (HR=0.58; 95% CI, 0.39–0.87; P=0.008), as confirmed by multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95% CI, 0.36–0.85; P=0.005). This effect was time dependent. Conclusion: In the 2.75 years prior to switching patients initially treated with tamoxifen to exemestane, a significant treatment-by-marker effect exists between AI/tamoxifen treatment and HER1-3 expression, suggesting HER expression could be used to select appropriate endocrine treatment at diagnosis to prevent or delay early relapses.
    British Journal of Cancer 10/2013; 109(9). DOI:10.1038/bjc.2013.609 · 4.82 Impact Factor

Publication Stats

6k Citations
1,251.31 Total Impact Points

Institutions

  • 2012–2015
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
    • University of Birmingham
      Birmingham, England, United Kingdom
  • 2007–2014
    • University of Nottingham
      Nottigham, England, United Kingdom
    • Novartis
      Bâle, Basel-City, Switzerland
  • 1994–2014
    • The University of Edinburgh
      • Edinburgh Cancer Research UK Centre
      Edinburgh, Scotland, United Kingdom
  • 1996–2012
    • University of Glasgow
      • Institute of Cancer Sciences
      Glasgow, Scotland, United Kingdom
  • 2007–2011
    • Edinburgh Sleep Centre
      Edinburgh, Scotland, United Kingdom
  • 1992–2011
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom
  • 2004
    • University of Tampere
      Tammerfors, Pirkanmaa, Finland