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Monitoring therapeutic response to neoadjuvant chemotherapy(NAC) is likely to improve NAC effectiveness in breast cancer(BC). Imaging performance seems to vary per tumour subtype(by ER and HER2 status), therefore we performed a systematic review on subtype specific imaging performance in monitoring NAC in BC. Studies examining imaging performance in predicting pathologic complete response(pCR) during NAC in BC subtypes were selected. Per study, negative- and positive predictive value, sensitivity(se) and specificity(sp), AUC and accuracy were derived. Fifteen/106 articles were included. Inter-study variability was revealed in: monitoring interval, response and pCR definitions. In ER-positive/HER2-negative BC, 181F FDG-PET/CT showed se/sp of 38%–89%/74%–100%, MRI showed se/sp of 35%–37%/87%–89%. In triple negative BC, 181F FDG-PET/CT showed se/sp of 0%–79%/95%–100%. 181F FDG-PET/CT showed in ER-positive/HER2-positive BC se/sp of 59%/80% and in ER-negative/HER2-positive 27%/88%. Evidence on imaging performance in monitoring NAC according BC subtypes is lacking. Consensus should be reached in: definitions of pCR, response and monitoring interval before starting well-designed studies.

Previous studies have shown that a “Preventive Exercise Program” (PREP) is cost-effective compared to the standard exercise program provided in “Usual Care” (UC) in patients with advanced head and neck cancer. The current paper specifically estimates the cost-effectiveness of the TheraBite jaw rehabilitation device (TB) which is used as part of the PREP, compared to Speech Language Pathology (SLP) sessions as part of UC, and herewith intents to inform reimbursement discussions regarding the TheraBite device. Costs and outcomes [quality-adjusted life-years (QALYs)] of the TB compared to SLP were estimated using a Markov model of advanced head and neck cancer patients. Secondary outcome variables were trismus, feeding substitutes, facial pain, and pneumonia. The incremental cost-effectiveness ratio (ICER) was estimated from a health care perspective of the Netherlands, with a time horizon of 2 years. The total health care costs per patient were estimated to amount to €5,129 for the TB strategy and €6,915 for the SLP strategy. Based on the current data, the TB strategy yielded more quality-adjusted life-years (1.28) compared to the SLP strategy (1.24). Thus, the TB strategy seems more effective (+0.04) and less costly (−€1,786) than the SLP only strategy. At the prevailing threshold of €20,000/QALY the probability for the TB strategy being cost-effective compared to SLP was 70 %. To conclude, analysis of presently available data indicates that TB is expected to be cost-effective compared to SLP in a preventive exercise program for concomitant chemo-radiotherapy for advanced head and neck cancer patients.

Background Next Generation Sequencing (NGS) is expected to lift molecular diagnostics in clinical oncology to the next level. It enables simultaneous identification of mutations in a patient tumor, after which targeted therapy may be assigned. This approach could improve patient survival and/or assist in controlling healthcare costs by offering expensive treatment to only those likely to benefit. However, NGS has yet to make its way into the clinic. Health Technology Assessment can support the adoption and implementation of a novel technology, but at this early stage many of the required variables are still unknown. Methods Scenario drafting and expert elicitation via a questionnaire were used to identify factors that may act as a barrier or facilitate adoption of NGS-based molecular diagnostics. Attention was paid to predominantly elicit quantitative answers, allowing their use in future modelling of cost-effectiveness. Results Adequately informing patients and physicians, the latters’ opinion on clinical utility and underlying evidence as well as presenting sequencing results within a relevant timeframe may act as pivotal facilitators. Reimbursement for NGS-based testing and accompanying therapies (both general and in case of off-label prescription) was found to be a potential barrier. Competition on the market and demonstrating clinical utility may also be challenging. Importantly, numerous quantitative values for variables related to each of these potential barriers/facilitators, such as such as desired panel characteristics, willingness to pay or the expected number of targets identified per person, were also elicited. Conclusions We have identified several factors that may either pose a barrier or facilitate the adoption of NGS in the clinic. We believe acting upon these findings, for instance by organizing educational events, advocating new ways of evidence generation and steering towards the most cost-effective solution, will accelerate the route from bench-to-bedside. Moreover, due to the methodology of expert elicitation, this study provides parameters that can be incorporated in future cost-effectiveness modeling to steer the development of NGS gene panels towards the most optimal direction. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2100-0) contains supplementary material, which is available to authorized users.

Purpose Guiding response to neoadjuvant chemotherapy (guided-NACT) allows for an adaptative treatment approach likely to improve breast cancer survival. In this study, our primary aim is to explore the expected cost-effectiveness of guided-NACT using as a case study the first randomized controlled trial that demonstrated effectiveness (GeparTrio trial). Materials and Methods As effectiveness was shown in hormone-receptor positive (HR+) early breast cancers (EBC), our decision model compared the health-economic outcomes of treating a cohort of such women with guided-NACT to conventional-NACT using clinical input data from the GeparTrio trial. The expected cost-effectiveness and the uncertainty around this estimate were estimated via probabilistic cost-effectiveness analysis (CEA), from a Dutch societal perspective over a 5-year time-horizon. Results Our exploratory CEA predicted that guided-NACT as proposed by the GeparTrio, costs additional €110, but results in 0.014 QALYs gained per patient. This scenario of guided-NACT was considered cost-effective at any willingness to pay per additional QALY. At the prevailing Dutch willingness to pay threshold (€80.000/QALY) cost-effectiveness was expected with 78% certainty. Conclusion This exploratory CEA indicated that guided-NACT (as proposed by the GeparTrio trial) is likely cost-effective in treating HR+ EBC women. While prospective validation of the GeparTrio findings is advisable from a clinical perspective, early CEAs can be used to prioritize further research from a broader health economic perspective, by identifying which parameters contribute most to current decision uncertainty. Furthermore, their use can be extended to explore the expected cost-effectiveness of alternative guided-NACT scenarios that combine the use of promising imaging techniques together with personalized treatments.

Both the 70-gene signature and the 21-gene assay are novel prognostic tests used to guide adjuvant chemotherapy decisions in patients with early breast cancer. Although the results of ongoing prospective trials will only become available in some years, the tests have already been included in clinical guidelines such as St. Gallen’s. In literature, the cost-effectiveness (CE) of both tests as compared to conventional prognostic tests has been described. We report on a direct comparison of CE; as different compliance rates were reported, we also taken these into account. A Markov decision model with a time horizon of 20 years was developed to assess the effects, costs and CE of three alternatives; 21-gene, 70-gene, and St. Gallen (SG) or Adjuvant Online (AO), dependent on the dataset used in patients with early, node-negative, breast cancer. Sensitivity and specificity were based on two datasets, incorporating compliances rates based on literature. For both datasets, whereas the 70-gene signature yielded more quality adjusted life years (QALYs) and was less costly; the 21-gene amounted more life years (LYs) but was more costly. The decision uncertainty surrounding the probability of CE of the Thomassen-series amounted 55% for both cost/LY and cost/QALY, for the Fan-series 80% for LY and 65% for QALYs. Taking reported compliance with discordant test results into account, in general, the effect of all strategies decreased, while the costs increased, without relatively influencing the CEA performance. This comparison indicates that the performances of the 70-gene and the 21-gene based on reported studies are close. The 21-gene has the highest probability of being cost-effective when focusing on cost/LY, while focusing on cost/QALY, the 70-gene signature was most cost-effective. The level of compliance can have serious impact on the CE. With additional data, preferably from head-to-head outcome studies and especially on compliance concerning discordant test results, calculations can be made with higher degrees of certainty.

We sought to compare the molecular signature of node negative cancers from two cohorts 15 years apart, to determine if there is molecular evidence of increase in low and ultralow risk cancers over time. We studied the impact of age, time period of diagnosis, and mammographic screening on biology of tumors where The Netherlands Cancer Institute 70-gene prognosis signature was generated as part of 2 validation series, one retrospective (1984-1992), Cohort 1, and one prospective (2004-2006), Cohort 2. A total of 866 patients were analyzed. Regardless of time period of diagnosis, the proportion of T1, grade 1, hormone receptor positive (HR) tumors, and good prognosis by 70-gene signature significantly increases as age increases (P < 0.01). In women aged 49-60, the time period of diagnosis significantly affects the proportion of cancers that were NKI 70-gene low risk: 40.6% (67/165) compared with 58% (119/205) for Cohorts 1 and 2, respectively. This is in contrast to the absence of a significant change for women under age 40, where 25% (17/68) and 30% (17/56) were low risk in Cohorts 1 and 2, respectively. In women aged 49-60, using an ultralow risk threshold of the 70-gene signature, 10% of tumors in Cohort 1 were ultralow risk compared with 30% for women with screen-detected cancers in Cohort 2. Older age and method of detection (screening) are associated with a higher likelihood of a biologically low risk tumor. In women over age 50, biologically low risk tumors are frequent and tools that classify risk may minimize overtreatment.

Smoking is the main causative factor for development of head and neck and lung cancer. In addition, other malignancies such as bladder, stomach, colorectal, kidney and pancreatic cancer have a causative relation with smoking. Continued smoking after having been diagnosed with cancer has many negative consequences: effectiveness of radiotherapy is diminished, survival time is shortened and risks of recurrence, second primary malignancies and treatment complications are increased. In view of the significant health consequences of continued smoking, therefore, additional support for patients to stop smoking seems a logical extension of the present treatment protocols for smoking-related cancers. For prospectively examining the effect of nursing-delivered smoking cessation programme for patients with head and neck or lung cancer, 145 patients with head and neck or lung cancer enrolled into this programme over a 2-year period. Information on smoking behaviour, using a structured, programme specific questionnaire, was collected at baseline, and after 6 and 12 months. At 6 months, 58 patients (40%) had stopped smoking and at 12 months, 48 patients (33%) still had refrained from smoking. There were no differences in smoking cessation results between patients with head and neck and lung cancer. The only significant factor predicting success was whether the patient had made earlier attempts to quit smoking. A nurse-managed smoking cessation programme for patients with head and neck or lung cancer shows favourable long-term success rates. It seems logical, therefore, to integrate such a programme in treatment protocols for smoking-related cancers.

Background: Genomic recurrence risk test results now inform clinical decisions about adjuvant treatment for women with early-stage breast cancer. We sought to understand patients' knowledge of these tests and correlates of their knowledge. Methods: Participants in this cross-sectional study were 78 women, treated for early-stage, estrogen receptor-positive breast cancer with 0–3 positive lymph nodes, whose medical records indicated they received Oncotype DX testing earlier. We mailed a questionnaire that assessed knowledge of genomic recurrence risk testing (13 item scale, alpha=0.83) and reviewed medical charts of consenting patients. Results: Knowledge about genomic recurrence risk testing was low (mean knowledge score=67%, SD=0.23). Low knowledge scores were more commonly due to responses of ‘don't know’ than incorrect answers. Most women (91%) clearly understood that test results can aid decisions about chemotherapy, and few (22%) understood that the test's estimate of the chance of metastasis assumes the patient is receiving hormone therapy. Higher knowledge about genomic recurrence risk testing was associated with higher education, reading ability, and numeracy. Knowledge was higher among women who recalled receiving both verbal and printed information about the test and among women who had active roles in deciding about their treatments. Higher knowledge was also associated with having fewer concerns about genomic testing. Discussion: Among early-stage breast cancer patients who received Oncotype DX, we found low knowledge about many aspects of genomic recurrence risk testing. Research is needed to understand testing information provided to patients and best practices for patient education. Copyright © 2010 John Wiley & Sons, Ltd.

Background: The 70-gene signature (MammaPrint (R)) is a prognostic test used to guide adjuvant treatment decisions in patients with node-negative breast cancer. In order to decide upon its use, a systematic comparative analysis of the effects of the 70-gene signature, the Sankt Gallen guidelines and the Adjuvant Online Software for these patients on survival, quality of life and costs is warranted. Methods: A Markov decision model was used to simulate the 20-year costs and outcomes (survival and quality-of-life adjusted survival (QALYs)) in a hypothetical cohort of node-negative, estrogen receptor positive breast cancer patients. Sensitivity and specificity of the three prognostic tools were based on 5 and 10 years breast cancer specific survival and distant metastasis as first event, derived from a pooled analysis consisting of 305 tumour samples from 3 previously reported validation studies concerning the 70-gene signature. Results: Small differences in survival, but substantial differences in quality-adjusted survival between the prognostic tools were observed. Quality-adjusted survival was highest when using the 70-gene signature. Based on costs per QALY, the 70-gene has the highest probability of being cost-effective for a willingness to pay for a QALY higher than (sic)4600. Sankt Gallen showed the highest survival rates compared to the 70-gene signature, but leads to a substantial larger amount of adjuvant chemotherapy and hence higher costs, thus demanding a willingness to pay of (sic)29.326 to save a life year. Conclusions: When deciding upon the cost-effectiveness of the prognostic tests, the 70-gene signature improves quality-adjusted survival and has the highest probability of being cost-effective.

Objectives:Constructive Technology Assessment (CTA) is a means to guide early implementation of new developments in society, and can be used as an evaluation tool for Coverage with Evidence Development (CED). We used CTA for the introduction of a new diagnostic test in the Netherlands, the 70-gene prognosis signature (MammaPrint®) for node-negative breast cancer patients.Methods:Studied aspects were (organizational) efficiency, patient-centeredness and diffusion scenarios. Pre-post structured surveys were conducted in fifteen community hospitals concerning changes in logistics and teamwork as a consequence of the introduction of the 70-gene signature. Patient-centeredness was measured by questionnaires and interviews regarding knowledge and psychological impact of the test. Diffusion scenarios, which are commonly applied in industry to anticipate on future development and diffusion of their products, have been applied in this study.Results:Median implementation-time of the 70-gene signature was 1.2 months. Most changes were seen in pathology processes and adjuvant treatment decisions. Physicians valued the addition of the 70-gene signature information as beneficial for patient management. Patient-centeredness (n= 77, response 78 percent): patients receiving a concordant high-risk and discordant clinical low/high risk-signature showed significantly more negative emotions with respect to receiving both test-results compared with concordant low-risk and discordant clinical high/low risk-signature patients. The first scenario was written in 2004 before the introduction of the 70-gene signature and identified hypothetical developments that could influence diffusion; especially the “what-if” deviation describing a discussion on validity among physicians proved to be realistic.Conclusions:Differences in speed of implementation and influenced treatment decisions were seen. Impact on patients seems especially related to discordance and its successive communication. In the future, scenario drafting will lead to input for model-based cost-effectiveness analysis. Finally, CTA can be useful as a tool to guide CED by adding monitoring and anticipation on possible developments during early implementation, to the assessment of promising new technologies.

To perform early Technology Assessment (TA) of nanotechnology in oncology. The possibilities of nanotechnology for detection (imaging), diagnosis and treatment of cancer are subject of different research programs where major investments are concerned. As a range of bio- nanotechnologies is expected to enter the oncology field it is relevant to consider the various aspects involved in especially early TA. This article provides two cases of early assessment of (predecessors of) nanotechnologies: Microarray Analysis and Photodynamic Therapy implementation, which methodology can be extrapolated to other nanotechnologies in oncology. Constructive Technology Assessment (CTA) is used for the introduction of technologies that are still in a dynamic phase of development or in an early stage of diffusion. The selection of studied aspects in CTA is based on: clinical aspects (safety, efficacy, and effectiveness), economic (cost-effectiveness), patient related (QoL, ethical/juridical and psychosocial), organizational aspects (diffusion and adoption) and scenario drafting. The features of the technology and the phase of implementation are decisive for choices and timing of the specific aspects to be studied. A framework was drafted to decide on the relevant aspects. In the first case, early implementation of Microarray Analysis; clinical effectiveness, logistics, patient centeredness and scenario drafting were given priority. Related to the diffusion-phase of Photodynamic Therapy however other aspects were evaluated, such as early cost-effectiveness analysis for possible reimbursement. Often CTA will result in a mixed method design. Especially scenario drafting is a powerful instrument to predict possible developments that can be anticipated upon in the assessment. CTA is appropriate for the study of early implementation of new technologies in oncology. In early TA small series often necessitate a mix of quantitative and qualitative methods. The features of nanotechnology involved are decisive for the selection of CTA aspects, most likely: safety -especially possible interactions with other technologies-, ethics, cost-effectiveness and patient centeredness.

In a recent report, Bonastre et al1 calculated the cost effectiveness of molecular profiling for adjuvant decision making in patients with node-negative breast cancer and concluded that, under the present circumstances in France, the 70-gene signature (MammaPrint) is unlikely to be cost effective.

Background: Metastatic melanoma has a poor prognosis with 10 year survival being < 5%. Standard therapy in the Netherlands is the effective but costly Ipilimumab. An emerging 1st line immunotherapy is Tumor Infiltrating Lymphocytes (TIL)-treatment, with response rates > 50% and expected survival rates of 25%-42% versus 45% (1yr) and 23.5% (2yr) for Ipilimumab. TIL is highly personalized, however complex and requests substantial upfront investments from the hospital in expensive lab-equipment, staff expertise and training. Therefore, an exploratory projection of its impact on patient outcomes and health care costs was made using health economic modelling. Methods: A Markov decision model including three health states (stable disease, progressive disease and death) was developed to estimate the expected costs and outcomes (quality adjusted life years; QALYs) for TIL versus Ipilimumab in metastatic melanoma patients from a societal perspective over a life long time horizon. Data sources include a pilot study and published literature. Technical failures and treatment non-compliance were incorporated in the analysis to reflect real world effectiveness. Results: TIL is expected to improve QALYs (+0.39) compared to Ipilimumab at higher incremental cost (+€12.416) with an ICER of €31.000/QALY. It has the highest probability of being cost-effective at WTP values of €30k/QALY (50% certainty) and higher, up to 90% certainty at a WTP of €80k/QALY. The model outcomes are most sensitive to changes in survival estimates. Conclusions: Based on an exploratory analysis,TIL is expected to improve QALYs compared to Ipilimumab at lower incremental cost and has the highest probability of being cost-effective. To reduce decision uncertainty, a future clinical trial to investigate survival should be prioritized.

Objectives: 18F-FDG-PET/CT is accurate in detecting distant metastases (DM) in breast cancer patients scheduled for neoadjuvant chemotherapy. If DMs are screen-detected in an early phase, morbidity and mortality may be reduced. Because 18F-FDG-PET/CT comes at a significant cost, we compared its expected cost-effectiveness in stage II/III breast cancer patients of the UK, the US and the Netherlands (NL) vs. the gold-standard (X-thorax/liver sonography/bone scan (UK/NL) and CT-thorax-abdomen/bone scan (US)). Methods: A time-dependent Markov model compared expected Life Year (LY) and cost/Quality-adjusted Life Year (QALY) gained in four breast cancer subtypes (ER-/HER2+;ER+/HER2+;ER-/HER2-;ER+/HER2-) over a 5-year time horizon from a hospital perspective. Sensitivity and specificity of imaging and type of systemic and local treatments were derived from the Netherlands Cancer Institute. Epidemiological, survival and utility data were estimated from literature or informed by expert assumptions. Costs (2013) were derived from national tariffs (UK and NL), and from the Centres for Medicaid and Medicare Services (US). Results: 18F-FDG-PET/CT is more sensitive (53% vs. 15%) and specific (97% vs. 94%) than the gold-standard. LYs and QALYs gained were similar across subtypes, ranging from 0.025 to 0.027 and 0.0037 to 0.0044 respectively. In all countries, ER+HER2+ was the least and ER+HER2- the most costly group. 18F-FDG-PET/CT is expected to be cost-effective in the NL and the US (with highest ICERs of €165/QALY in ER+/HER2+ and $750 in ER-HER2+), with probabilities of cost-effectiveness ranging from 46-52% and 62-72% respectively, but not in the UK, with a 66-75% probability, depending on tumor subtype. Conclusions: Using 18F-FDG-PET/CT for DM screening in stage II/III breast cancer is expected to result in incremental QALY gains in all subtypes and countries. Due to costs differences between countries, 18F-FDG-PET/CT is expected to be cost-effective in the US and the NL, but not in the UK.

Background: The objective of this population-based study was to assess patient, physician and tumour determinants associated with positive surgical margins after prostatectomy, and to assess the effects of positive surgical margins on prostate cancer-specific survival. Methods: We included 1’254 prostate cancer patients recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990–2008. To assess factors associated with positive margins, we used logistic regression. We assessed the effects of positive margins on prostate cancer-specific survival by Cox proportional hazard models accounting for numerous other prognostics factors including prostate and tumour volume, the total percentage of tumour, radiotherapy, surgical approach and surgeon’s caseload. Results: Among men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate logistic regression analysis, period, clinical- and pathological T stage, Prostate Specific Antigen (PSA) level, Gleason score and percentage of tumour in the prostate were significantly associated to positive margins. Ten-year prostate cancer-specific survival was 96.6% for the negative margins group and 92.0% for the positive margins group (log rank p = 0.008). In the Cox survival analysis adjusted for tumour characteristics, surgical margin status per se was not an independent prognostic factor while age, pathological T, PSA level and Gleason score remained associated with prostate cancer-specific survival. Conclusions: More aggressive tumour characteristics were strong determinants for positive margins. Furthermore, surgical margin status per se was not an independent prognostic factor for prostate cancer-specific survival after adjusting by the gravity of the disease in the multivariate analysis.

Objectives: To estimate the expected benefits from a pivotal randomised controlled trial of predictive biomarkers for high dose alkylating chemotherapy (HDAC) in triple negative breast cancer (TNBC) and to inform decisions about the design and priority of further studies. Methods: A markov decision model compared treating 40- years old TNBC women with HDAC based on four predictive biomarker strategies: 1) BRCA1-like by MLPA testing; 2) BRCA1-like by aCGH testing, 3) strategy 1 followed by XIST and 53BP1 testing; and 4) strategy 2 followed by XIST and 53BP1 testing, versus treating all patients with standard chemotherapy. A Dutch societal perspective and a 20-year time horizon were used. Input data came from literature and expert opinions. We assessed four primary outcomes: the expected value of (partial) perfect information (EV (P) PI), the expected value of sample information (EVSI) and the expected net benefit of sampling (ENBS) for the ongoing pivotal TNM trial (NCT01057069) and/or potential future studies. Results: The population EVPI was €663 million (M). The EVPPI suggests prioritizing further research towards effectiveness parameters, specifically prevalence and positive predictive value of the biomarkers; response rates in biomarker negative patients and TNBC unclassified patients, which are estimated to collectively have a value of information of circa €630M. The value of further research on transition probabilities is estimated at € 41M, followed by utilities at €34M and costs at €34M. Further information on transition probabilities could be gathered from the TNM trial and that of effectiveness parameters and costs from accompanying studies to this trial, altogether estimated to have an ENBS of €657 M. Conclusions: Further research on predictive biomarkers for HDAC should focus on gathering transition probability data from the current TNM trial, and on accompanying studies to derive data on other effectiveness parameters and costs.

Objectives: Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether treating TNBC with personalized HDAC based on BRCA1-like testing can be more cost-effective than current clinical practice. Additionally we estimated the minimum required prevalence of BRCA1-likeness and the required positive predictive value (PPV) for a BRCA1-like test to render this strategy cost-effective. Methods: Our markov model compared the outcomes of treating TNBC women with personalized HDAC based on BRCA1-like testing vs. current clinical practice from a societal Dutch perspective and a 20-year time horizon. From our base-case model we assessed: 1) the incremental number of respondents; 2) the incremental number of Quality Adjusted Life Years, 3) the incremental costs, and 4) the incremental cost-effectiveness ratio (ICER). We performed one-way sensitivity analysis (SA) of all model parameters, and two-way SA of prevalence and PPV. Data were obtained from a current trial (NCT01057069), published literature and expert opinions where necessary. Results: Based on our base-case analysis with 68% BRCA1-like prevalence, 100% PPV, and costs of € 164 / test, treating TNBC according to BRCA1-like testing would be cost-effective (€16.192/QALY). One-way SA on the prevalence and PPV demonstrated that only the PPV drives the ICER changes. In two-way SA, the lower bound for the two parameters was: prevalence 39.6% and PPV 46.4%. Regardless of prevalence, at PPVs > 46.4% BRCA1-like testing was always cost-effective. Conclusions: Treating TNBC with personalized HDAC based on BRCA1-like testing is expected to be cost-effective at a minimum PPV of 46%. This information can help test developers in decisions on further research and development

Background: In early stage breast cancer patients, with axillary lymph node metastasis, the 70-gene signature, MammaPrint® (MP) identifies patients with a High or Low Risk of distant breast cancer (BC) recurrence. For MP Low Risk (G(enomic)-low) in patients with up to 3 positive lymph nodes (N1-3), the MINDACT trial (Cardoso, NEJM 2016) showed that it might be safe to forgo adjuvant chemotherapy. Here we evaluated the prognostic value of MP at 10 years follow-up in patients with lymph node positive early stage BC. Methods: Between 2004 and 2006 812 women with early stage BC participated in the observational RASTER trial (Bueno de Mesquita, Lancet Oncol, 2007). 181 patients were node positive and not included in the primary analysis, 176 of them gave consent for future research. On 164 tumor samples (FFPE) MP was performed retrospectively. Survival data was collected and samples were allocated to clinical high (C-high) or C-low risk as used in MINDACT. Patients with over 3 axillary lymph node metastases (N4+) were all considered C-high. 10-year distant-recurrence-free-interval (DRFI) was compared between subgroups based on the MP and clinical assessment. Results: In 3 patients the clinical assesment could not be determined. Over 95% of patients received chemotherapy, 82.9% (136/164) of tumors were ER-positive and 18.3% (30/164) of patients had N4+. MP identified 47% (n = 77/164) as Low Risk, including 16,9% (13/77) with N4+. 10-year DRFI in patients N1-3 and G-Low or G-High was 94.9% and 80.7% respectively (HR 4.7; 95%CI 1.3-16.2). With the clinical assessment 13.7% (n = 22/161) were low risk, only one was diagnosed with distant BC recurrence. 10-years DRFI was 94.4% in C-low and 85.8% in C-high (HR 3.7 95%CI 0.5-28.5). In N4+ 10-years DRFI was 69.7%. Combining the clinical assessment with MP risk assessment in patients N1-3 the 10-years DRFI in clinical high risk patients was 95.2% for G-Low (n = 44) and 79.6% for G-High (n = 65) (HR 4.83 95%CI 1.1-21.4). Conclusions: We again confirm the prognostic value of Mammaprintin BC patients with axillary lymph node involvement after 10 years follow up. In N1-3 patients with clinical high risk, MP can identify a subgroup with excellent prognosis after standard adjuvant systemic therapy

Clinical guidelines for breast cancer treatment differ in their selection of patients at a high risk of recurrence who are eligible to receive adjuvant systemic treatment (AST). The 70-gene signature is a molecular tool to better guide AST decisions. The aim of this study was to evaluate whether adding the 70-gene signature to clinical risk prediction algorithms can optimize outcome prediction and consequently treatment decisions in early stage, node-negative breast cancer patients. A 70-gene signature was available for 427 patients participating in the RASTER study (cT1-3N0M0). Median follow-up was 61.6 months. Based on 5-year distant-recurrence free interval (DRFI) probabilities survival areas under the curve (AUC) were calculated and compared for risk estimations based on the six clinical risk prediction algorithms: Adjuvant! Online (AOL), Nottingham Prognostic Index (NPI), St. Gallen (2003), the Dutch National guidelines (CBO 2004 and NABON 2012), and PREDICT plus. Also, survival AUC were calculated after adding the 70-gene signature to these clinical risk estimations. Systemically untreated patients with a high clinical risk estimation but a low risk 70-gene signature had an excellent 5-year DRFI varying between 97.1 and 100 %, depending on the clinical risk prediction algorithms used in the comparison. The best risk estimation was obtained in this cohort by adding the 70-gene signature to CBO 2012 (AUC: 0.644) and PREDICT (AUC: 0.662). Clinical risk estimations by all clinical algorithms improved by adding the 70-gene signature. Patients with a low risk 70-gene signature have an excellent survival, independent of their clinical risk estimation. Adding the 70-gene signature to clinical risk prediction algorithms improves risk estimations and therefore might improve the identification of early stage node-negative breast cancer patients for whom AST has limited value. In this cohort, the PREDICT plus tool in combination with the 70-gene signature provided the best risk prediction. Electronic supplementary material The online version of this article (doi:10.1007/s10549-014-2954-2) contains supplementary material, which is available to authorized users.

Background Gene expression profiling (GEP) is increasingly used in the rapidly evolving field of personalized medicine. We sought to evaluate the association between GEP-assessed of breast cancer recurrence risk and patients’ well-being. Methods Participants were Dutch women from 10 hospitals being treated for early stage breast cancer who were enrolled in the MINDACT trial (Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy). As part of the trial, they received a disease recurrence risk estimate based on a 70-gene signature and on standard clinical criteria as scored via a modified version of Adjuvant! Online. \Women completed a questionnaire 6–8 weeks after surgery and after their decision regarding adjuvant chemotherapy. The questionnaire assessed perceived understanding, knowledge, risk perception, satisfaction, distress, cancer worry and health-related quality of life (HRQoL), 6–8 weeks after surgery and decision regarding adjuvant chemotherapy. Results Women (n = 347, response rate 62%) reported high satisfaction with and a good understanding of the GEP information they received. Women with low risk estimates from both the standard and genomic tests reported the lowest distress levels. Distress was higher predominately among patients who had received high genomic risk estimates, who did not receive genomic risk estimates, or who received conflicting estimates based on genomic and clinical criteria. Cancer worry was highest for patients with higher risk perceptions and lower satisfaction. Patients with concordant high-risk profiles and those for whom such profiles were not available reported lower quality of life. Conclusion Patients were generally satisfied with the information they received about recurrence risk based on genomic testing. Some types of genomic test results were associated with greater distress levels, but not with cancer worry or HRQoL. Trial registration ISRCTN: ISRCTN18543567

Item does not contain fulltext OBJECTIVE: This article provides a systematic and critical review of the evolving methods and applications of value of information (VOI) in academia and practice and discusses where future research needs to be directed. METHODS: Published VOI studies were identified by conducting a computerized search on Scopus and ISI Web of Science from 1980 until December 2011 using pre-specified search terms. Only full-text papers that outlined and discussed VOI methods for medical decision making, and studies that applied VOI and explicitly discussed the results with a view to informing healthcare decision makers, were included. The included papers were divided into methodological and applied papers, based on the aim of the study. RESULTS: A total of 118 papers were included of which 50 % (n = 59) are methodological. A rapidly accumulating literature base on VOI from 1999 onwards for methodological papers and from 2005 onwards for applied papers is observed. Expected value of sample information (EVSI) is the preferred method of VOI to inform decision making regarding specific future studies, but real-life applications of EVSI remain scarce. Methodological challenges to VOI are numerous and include the high computational demands, dealing with non-linear models and interdependency between parameters, estimations of effective time horizons and patient populations, and structural uncertainties. CONCLUSION: VOI analysis receives increasing attention in both the methodological and the applied literature bases, but challenges to applying VOI in real-life decision making remain. For many technical and methodological challenges to VOI analytic solutions have been proposed in the literature, including leaner methods for VOI. Further research should also focus on the needs of decision makers regarding VOI.

Constructive Technology Assessment (CTA) can be used as a complementary approach to Health Technology Assessment (HTA), especially for the early and dynamic introduction of new technologies in a controlled way. CTA is based on the idea that during the course of technology development, choices are constantly being made about the form, the function, and the use of that technology. In this dissertation the mixed method approach of CTA covers an integral assessment of clinical, economic, patient-related, ethical/juridical, and organizational domains. Diffusion scenarios, which are commonly applied in industry to anticipate on their strategies concerning future development, have been adapted to monitor the dynamics in this study. The aim of this dissertation was to contribute to the knowledge on early stage HTA by performing a CTA for the introduction and diffusion of gene expression profiling for breast cancer patients. As a clinical case, the introduction and diffusion of the 70-gene prognosis signature (MammaPrintTM) using microarray analysis was evaluated. The research objectives were twofold: first to develop the CTA method in early stages of technology development and second, to apply the CTA method to the case of the 70-gene signature for breast cancer, in order to support and anticipate on the introduction of this new diagnostic test, specified in different CTA aspects. This study showed that the CTA methodology can be a useful tool to guide controlled early implementation of a promising technology and its possible use for coverage decisions, in this case the 70-gene signature for breast cancer patients. The patient information regarding the 70-gene signature appeared to be clear and satisfactory and resulted in a good understanding of (the consequences of) the genomic profile. In general, the 70-gene signature seems most cost-effective in terms of quality adjusted life years; the slightly more sensitive tests deliver more life years, but leads to a substantial larger amount of adjuvant chemotherapy and hence higher costs, thus demanding a higher willingness to pay. Developing the 70-gene signature based on paraffin instead of fresh frozen tissue could establish a higher cost-effectiveness and could thus be a worthwhile investment. Finally, when incorporating scenarios in the decision model, it became apparent that early anticipation on certain aspects is necessary to reach the potential costeffectiveness.

Background Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective. Methods A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research. Results PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to €41,986 and for PREP to €42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least €3,200/QALY. At the prevailing threshold of €20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty. Conclusions Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till €45,906/QALY).

Background: Mammographic screening and increased awareness has led to an increase in the detection of T1 breast tumors that are generally estimated as having low risk of recurrence after locoregional treatment. However, even small tumors can metastasize, which leaves us with the question for the necessity of adjuvant treatment. Therefore, additional prognostic markers are needed to tailor adjuvant systemic treatment for these relatively low-risk patients. The aim of our study was to evaluate the accuracy of the 70-gene MammaPrint signature in T1 breast cancer. Materials and Methods: We selected 964 patients from previously reported studies with pT1 tumors (≤2 cm). Frozen tumor samples were hybridized on the 70-gene signature array at the time of the initial study and classified as having good prognosis or poor prognosis. Results: The median follow-up was 7.1 years (range 0.2-25.2). The 10-year distant metastasis-free (DMFS) and breast cancer specific survival (BCSS) probabilities were 87% (SE 2%) and 91% (SE 2%), respectively, for the good prognosis-signature group (n = 525), and 72% (SE 3%) and 72% (SE 3%), respectively, for the poor prognosis-signature group (n = 439). The signature was an independent prognostic factor for BCSS at 10 years (multivariate hazard ratio [HR] 3.25 [95% confidence interval, CI, 1.92-5.51; P < .001]). Moreover, the 70-gene MammaPrint signature predicted DMFS at 10 years for 139 patients with pT1ab cancers (HR 3.45 [95% CI 1.04-11.50, P = .04]). Conclusions: The 70-gene MammaPrint signature is an independent prognostic factor in patients with pT1 tumors and can help to individualize adjuvant treatment recommendation in this increasing breast cancer population.

Genomic recurrence risk test results now inform clinical decisions about adjuvant treatment for women with early-stage breast cancer. We sought to understand patients' knowledge of these tests and correlates of their knowledge.Participants in this cross-sectional study were 78 women, treated for early-stage, estrogen receptor-positive breast cancer with 0-3 positive lymph nodes, whose medical records indicated they received Oncotype DX testing earlier. We mailed a questionnaire that assessed knowledge of genomic recurrence risk testing (13 item scale, alpha=0.83) and reviewed medical charts of consenting patients.Knowledge about genomic recurrence risk testing was low (mean knowledge score=67%, SD=0.23). Low knowledge scores were more commonly due to responses of 'don't know' than incorrect answers. Most women (91%) clearly understood that test results can aid decisions about chemotherapy, and few (22%) understood that the test's estimate of the chance of metastasis assumes the patient is receiving hormone therapy. Higher knowledge about genomic recurrence risk testing was associated with higher education, reading ability, and numeracy. Knowledge was higher among women who recalled receiving both verbal and printed information about the test and among women who had active roles in deciding about their treatments. Higher knowledge was also associated with having fewer concerns about genomic testing.Among early-stage breast cancer patients who received Oncotype DX, we found low knowledge about many aspects of genomic recurrence risk testing. Research is needed to understand testing information provided to patients and best practices for patient education.

Recent developments in genomics have resulted in the increased availability of gene profiles for early diagnosis and prognosis in breast cancer. A request from a Dutch woman to have her tumour tissue tested years after treatment confronted the Netherlands Cancer Institute (NKI) and its staff with legal, ethical, and practical questions regarding patients' rights in relation to residual tissue storage and its use for clinical purposes. Was her tissue still available? If so, could she demand that the test be carried out or her tissue be transferred to another hospital? As it became apparent that appropriate guidance was lacking in this area, we developed guidelines on the issue, with the involvement of relevant professionals and patient representatives within the framework of a Technology Assessment project.1 Gene-expression profiling is an important development that is likely to predict the diagnosis and prognosis of malignant disease more accurately than existing clinicopathological parameters.2 Although gene-expression profiling is not yet routine, several tests are already applied in clinical practice. Additionally, the 70-gene signature (MammaPrint), which uses microarrays on fresh frozen tumour tissue, is being tested in a multicentre randomised trial (MINDACT).3 However, for such tests to be successful it is essential that sufficient tumour tissue is available.

Nanotechnology is expected to play an increasingly important role in the diagnostics, prognostics, and management of targeted cancer treatments. While papers have described promising results for nanotechnology in experimental settings, the translation of fundamental research into clinical applications has yet to be widely adopted. In future, policy makers will need to anticipate new developments for clinical implementation and introduce technology assessments. Here we present an overview of the literature on the technology assessments that have already been undertaken on early stage nanotechnology in cancer care, with particular emphasis placed on clinical efficacy, efficiency, logistics, patient-related features and technology dynamics. Owing to the current stage of development of most nanotechnologies, we found only a limited number of publications describing the application of either Health Technology Assessment (HTA) or Constructive Technology Assessment (CTA). In spite of the promising conclusions of most papers concerning the benefits of clinical implementation, actual clinically relevant applications were rarely encountered, and so far only a few publications report application of systematic forms of technology assessment. Most articles consider aspects of environmental safety, regulation and ethics, often mentioning the need to investigate such issues more thoroughly. Evaluation of financial and organizational aspects is often missing. In order to obtain a realistic perspective on the translation and implementation process there is a need for a broad and systematic evaluation of nanotechnologies at early stages of development. Assessment methods taking technology dynamics into account, such as Constructive Technology Assessment (CTA) should be considered for evaluation purposes.

Summary Background A microarray-based 70-gene prognosis signature might improve the selection of patients with node-negative breast cancer for adjuvant systemic treatment. The main aims of this MicroarRAy PrognoSTics in Breast CancER (RASTER) study were to assess prospectively the feasibility of implementation of the 70-gene prognosis signature in community-based settings and its effect on adjuvant systemic treatment decisions when considered with treatment advice formulated from the Dutch Institute for Healthcare Improvement (CBO) and other guidelines. Methods Between January, 2004 and December, 2006, 812 women aged under 61 years with primary breast carcinoma (clinical T1–4N0M0) were enrolled. Fresh tumour samples were collected in 16 hospitals in the Netherlands within 1 h after surgery. Clinicopathological factors were collected and microarray analysis was done with a custom-designed array chip that assessed the mRNA expression index of the 70 genes previously identified for the prognostic signature. Patients with a "good" signature were deemed to have a good prognosis and, therefore, could be spared adjuvant systemic treatment with its associated adverse effects, whereas patients with a "poor" signature were judged to have a poor prognosis and should be considered for adjuvant systemic treatment. Concordance between risk predicted by the prognosis signature and risk predicted by commonly used clinicopathological guidelines (ie, St Gallen guidelines, Nottingham Prognostic Index, and Adjuvant! Online) was assessed. Findings Of 585 eligible patients, 158 patients were excluded because of sampling failure (n=128) and incorrect procedure (n=30). Prognosis signatures were assessed in 427 patients. The 70-gene prognosis signature identified 219 (51%) patients with good prognosis and 208 (49%) patients with poor prognosis. The Dutch CBO guidelines identified 184 patients (43%) with poor prognosis, which was discordant with those findings obtained with the prognosis signature in 128 (30%) patients. Oncologists recommended adjuvant treatment in 203 (48%) patients based on Dutch CBO guidelines, in 265 (62%) patients if the guidelines were used with the prognosis signature, and in 259 (61%) patients if Dutch CBO guidelines, prognosis signature, and patients' preferences for treatment were all taken into account. Adjuvant! Online guidelines identified more patients with poor prognosis than did the signature alone (294 [69%]), and discordance with the signature occurred in 160 (37%) patients. St Gallen guidelines identified 353 (83%) patients with poor prognosis with the signature and discordance in 168 (39%) patients. Nottingham Prognostic Index recorded 179 (42%) patients with poor prognosis with the signature and discordance in 117 (27%) patients. Interpretation Use of the prognosis signature is feasible in Dutch community hospitals. Adjuvant systemic treatment was advised less often when the more restrictive Dutch CBO guidelines were used compared with that finally given after use of the prognosis signature. For the other guidelines assessed, less adjuvant chemotherapy would be given when the data based on prognosis signature alone are used, which might spare patients from adverse effects and confirms previous findings. Future studies should assess whether use of the prognosis signature could improve survival or equal survival while avoiding unnecessary adjuvant systemic treatment without affecting patients' survival, and further assess the factors that physicians use to recommend adjuvant systemic treatment.

Background: Next Generation Sequencing (NGS) promises to find mutations (targets) in individual cancer patients, to subsequently prescribe targeted therapy. Currently, NGS is in development, the effects on choice of therapy and prognosis are still unclear, and the costs for targeted therapies are high. To accelerate the reimbursement process of NGS and potential new targeted therapies, and have a NGS-panel available for patients in the earliest possible stage, early Technology Assessment (TA) is performed to inform policy making around NGS in the Netherlands. One of the aims of the TA was to conduct a cost-effectiveness analysis. Methods: We constructed a target-based decision model (H-TArget) to estimate the cost-effectiveness of NGS versus single- and no testing. Standard- and targeted therapies in first and second line for 9 targets (BRAF, KRAS, NRAS, EGFR, ERBB/HER, MET, ROS, ALK, RET) over 3 tumor types (melanoma, non-small-cell lung cancer (NSCLC), colorectal cancer (CRC)) were incorporated. A Dutch healthcare perspective and a 5-year time horizon were adopted. Outcomes were incremental cost-effectiveness ratios (ICER) expressed in {euro}/quality adjusted life year (QALY). The threshold for cost-effectiveness is 80k in the Netherlands, which means that the concerning technology is cost-effective if the ICER is below this threshold. Expected Value of Partial Perfect Information (EVP(P)I) was calculated to quantify the value of further research into particular subsets of uncertain parameters. Results: The expected ICER was {euro}65k/QALY for melanoma, {euro}188k/QALY for NSCLC, and {euro}103k/QALY for CRC. As a weighted average to the three populations, the overall ICER yielded {euro}160k/QALY. The EVPI was {euro}25M for melanoma, the subsets of parameters to focus on in future research were: {euro}2M together for failures, prevalence, survival, and {euro}23M for costs. Conclusions: At the moment, using NGS is only cost-effective for melanoma. This is mostly due to the high costs of targeted therapies and the fact that the effects are still small. Based on our findings, industry should strive for a significant cost reduction of targeted therapies or achieve a spectacular improvement in effectiveness, which could improve the cost-effectiveness.

Background Health Technology Assessment (HTA) information, and in particular cost-effectiveness data is needed to guide decisions, preferably already in early stages of technological development. However, at that moment there is usually a high degree of uncertainty, because evidence is limited and different development paths are still possible. We developed a multi-parameter framework to assess dynamic aspects of a technology -still in development-, by means of scenario drafting to determine the effects, costs and cost-effectiveness of possible future diffusion patterns. Secondly, we explored the value of this method on the case of the clinical implementation of the 70-gene signature for breast cancer, a gene expression profile for selecting patients who will benefit most from chemotherapy. Methods To incorporate process-uncertainty, ten possible scenarios regarding the introduction of the 70-gene signature were drafted with European experts. Out of 5 most likely scenarios, 3 drivers of diffusion (non-compliance, technical failure, and uptake) were quantitatively integrated in a decision-analytical model. For these scenarios, the cost-effectiveness of the 70-gene signature expressed in Incremental Cost-Effectiveness Ratios (ICERs) was compared to clinical guidelines, calculated from the past (2005) until the future (2020). Results In 2005 the ICER was €1,9 million/quality-adjusted-life-year (QALY), meaning that the 70-gene signature was not yet cost-effective compared to the current clinical guideline. The ICER for the 70-gene signature improved over time with a range of €1,9 million to €26,145 in 2010 and €1,9 million to €11,123/QALY in 2020 depending on the separate scenario used. From 2010, the 70-gene signature should be cost-effective, based on the combined scenario. The uptake-scenario had strongest influence on the cost-effectiveness. Conclusions When optimal diffusion of a technology is sought, incorporating process-uncertainty by means of scenario drafting into a decision model may reveal unanticipated developments and can demonstrate a range of possible cost-effectiveness outcomes. The effect of scenarios give additional information on the speed with cost effectiveness might be reached and thus provide a more realistic picture for policy makers, opinion leaders and manufacturers.

1520 Background: 25 years of population-based screening have led to a sustained increase in the incidence of breast cancer, largely due to an increase in the rate of node-negative disease. A concom...

1525 Background: Since the advent of screening, breast cancer incidence has significantly increased in the United States as well as other countries. SEER data from the US shows that the increase is largely in localized disease without a concomitant or significant decrease in regionalized disease. In addition, the increase has occurred essentially in women over 50. We asked whether molecular characterization of tumors would shed light on the types of tumors detected in screening and in locally advanced breast cancers (LABC). Methods: We identified two groups of patients from European studies before and after the introduction of population based screened (in 1995) where the 70-gene prognosis test (MammaPrint) results were available. The first source is the European Validation Study (EVS) (Buyse et al, J Natl Cancer Inst. 2006). The second was a prospective implementation trial of MammaPrint in the Netherlands (RASTER study) (Bueno de Mesquita et al, Lancet Oncol. 2007). The source of LABC patients comes from the multicenter I-SPY TRIAL (CALGB 150007/150012) who underwent routine screening (prior mammogram within 2 years of diagnosis). Results: In women age 50–60, the fraction of cancers that were MammaPrint good prognosis were 40% and 60% prior to and after the introduction of screening, respectively. For women 50–60 who were actually undergoing screening, the fraction of tumors that were MammaPrint good prognosis was 67%. For patients aged 30–40 with stage I and II lymph node-negative disease, who did not undergo screening in either period, the fraction of MammaPrint good prognosis tumors did not change (29% and 31%, for EVS and Raster, respectively). For patients with LABC, from the I-SPY TRIAL, the fraction of tumors that are MammaPrint good prognosis is 7% and 29% for women aged 30–40 and 50–60, respectively. Of the LABC patients undergoing screening, 80% presented clinically during the interval between routine mammograms. Conclusions: Current screening programs are increasing the burden of low-risk cancers. Screening programs should consider including molecular profiles at the time of diagnosis to reduce overtreatment. The majority of LABCs have high-risk molecular profiles and do not present as screen detected cancers. New strategies are needed for early detection of LABC. [Table: see text]

518 Background: Small breast cancers are often considered as low risk tumors in clinico-pathologic risk assessment and treatment guidelines. However, since the ability to metastasize is an early and inherent genetic property of breast cancer and consequently even small tumors can metastasize, identification of prognostic subgroups for patients with small tumors would help to optimize treatment strategies. In the present study the 70-gene prognosis signature (MammaPrint), validated as independent prognostic indicator for node-negative and positive patients, was used to assess prognosis for pT1 breast cancer. Methods: 965 tumor samples of women with pT1 breast cancer from 7 previously reported studies were analyzed and classified by MammaPrint as good or poor prognosis. 10-year distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) was analyzed according to the 70-gene prognosis signature separately for pT1a/b (1–10mm) and pT1c (11–20mm) tumors. Results: Median follow-up was 7.1 years (range 0.2–25.2). 526 of 965 patients (55%) were classified as good prognosis and 439 (45%) as poor prognosis by the 70-gene signature. 562 patients (59%) received no adjuvant treatment, 19% received hormonal treatment only, 10% chemotherapy only and 12% both respectively. The 70-gene signature accurately predicted differences in 10-year DDFS (HR 2.7 [1.9–3.9], p [Table: see text]

Abstract #1084 Introduction: Risk assessment for breast cancer patients differs substantially among treatment guidelines. The NCCN, St.Gallen, Adjuvant!Online, and Dutch 2008 guidelines are less restrictive in comparison to the 2004 Dutch guidelines and Nottingham Prognostic Index, when selecting patients for adjuvant systemic treatment. The Dutch Institute for Healthcare Improvement (CBO) has introduced slight changes in the concept 2008 guidelines. Adjuvant systemic treatment is only advised when the absolute 10-years survival benefit is 5% or more. The new recommendations for adjuvant systemic treatment are based on survival tables used in the Adjuvant! software. The changes affect only node-negative patients aged 35 years: since 2008 patients with G2/G3 tumors >1cm or every tumor >2cm are advised to undergo adjuvant systemic therapy, while in 2004 this was the case for tumors G3>1cm, G2>2cm or every tumor >3cm. Patients and Methods: Risk was assessed for 427 lymph-node negative (LNN) patients in the prospective RASTER-study (Bueno-de-Mesquita, 2007) and 151 LNN patients in the NEJM-series (van de Vijver, 2002). Clinical risk was calculated using the 2004 and 2008 Dutch guidelines. Genetic risk was assigned according to the result of the Amsterdam 70-gene signature. Survival analyses were done according to the univariate Kaplan-Meier-method. Results: Instead of 57% in 2004, in 2008 only 24% of patients were assigned to clinical low risk in the RASTER study, and 141 patients (33%) changed from low to high risk (p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1084.

6575 Background: A Constructive Technology Assessment (CTA) in the early phase of controlled implementation of the 70-gene prognosis signature (MammaPrint™) for node-negative breast cancer in commu...