Jelle Wesseling

Publications (119) View all

• Article: Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers.

  E H Lips, L Mulder, A Oonk, L E van der Kolk, F B L Hogervorst, A L T Imholz, J Wesseling, S Rodenhuis, P M Nederlof
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  ABSTRACT: Background:BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness characteristics frequencies in a large cohort of triple-negative breast cancers (TNBCs).Methods:As a measure of BRCAness, we determined a specific BRCA1-like pattern by array Comparative Genomic Hybridisation (aCGH), and BRCA1 promoter methylation in 377 TNBCs, obtained from 3 different patient cohorts. Clinicopathological data were available for all tumours, BRCA1-germline mutation status and chemotherapy response data were available for a subset.Results:Of the tumours, 66-69% had a BRCA1-like aCGH profile and 27-37% showed BRCA1 promoter methylation. BRCA1-germline mutations and BRCA1 promoter methylation were mutually exclusive events (P=1 × 10(-5)). BRCAness was associated with younger age and grade 3 tumours. Chemotherapy response was significantly higher in BRCA1-mutated tumours, but not in tumours with BRCAness (63% (12 out of 19) vs 35% (18 out of 52) pathological complete remission rate, respectively).Conclusion:The majority of the TNBCs show BRCAness, and those tumours share clinicopathological characteristics with BRCA1-mutated tumours. A better characterisation of TNBC and the presence of BRCAness could have consequences for both hereditary breast cancer screening and the treatment of these tumours.British Journal of Cancer advance online publication, 4 April 2013; doi:10.1038/bjc.2013.144 www.bjcancer.com.
  British Journal of Cancer 04/2013; · 5.04 Impact Factor
• Article: A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study.

  C A Drukker, J M Bueno-de-Mesquita, V P Retèl, W H van Harten, H van Tinteren, J Wesseling, R M H Roumen, M Knauer, L J van 't Veer, G S Sonke, E J T Rutgers, M J van de Vijver, S C Linn
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  ABSTRACT: The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1-3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature, and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n=219) and high-risk (n=208) patients were 97·0% and 91·7%. The 5-year DRFI probabilities for AOL low-risk (n=132) and high-risk (n=295) patients were 96·7% and 93·4%. For 70-gene signature low-risk - AOL high-risk patients (n=124), of whom 76% (n=94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinic-pathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.
  International Journal of Cancer 01/2013; · 5.44 Impact Factor
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  Available from: Jelle Wesseling

  Article: Is DCIS Breast Cancer, and How Do I Treat it?

  N Bijker, M Donker, J Wesseling, G J den Heeten, E J Th Rutgers
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  ABSTRACT: OPINION STATEMENT: Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer with a heterogeneous clinical behaviour. Since the introduction of mammographic screening programmes, the incidence of DCIS has shown a dramatic increase. Treatment should focus on the prevention of progression to invasive disease. If progression occurs, poorly differentiated DCIS frequently gives rise to grade III invasive breast cancer, whereas well differentiated DCIS more often recurs as grade I invasive disease. However, at present, validated diagnostic test are lacking to predict progression accurately. The majority of women with DCIS are suitable for breast conserving therapy. Obtaining clear surgical margins is the most important goal of a local excision. Radiotherapy is effective in reducing the risk of local recurrence with about 50 % in all subgroups of patients with DCIS. (Breast cancer specific) survival of women with DCIS is excellent, and radiotherapy does not further improve this. Future research should be directed in enabling to select women who have a high risk of-invasive-recurrence, so in which radiotherapy should be standard part of the breast conserving approach, and those women with a more indolent lesion, in which after surgery a watchful waiting approach can be followed.
  Current Treatment Options in Oncology 12/2012; · 2.68 Impact Factor
• Article: Optical sensing for tumor detection in the liver.

  D J Evers, R Nachabé, D Hompes, F van Coevorden, G W Lucassen, B H W Hendriks, M-L F van Velthuysen, J Wesseling, T J M Ruers
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  ABSTRACT: BACKGROUND: There is an increasing trend for optical guidance techniques in surgery. Optical imaging using Diffuse Reflectance Spectroscopy (DRS) can distinguish different tissue types through a specific "optical fingerprint". We investigated whether DRS could discriminate metastatic tumor tissue from normal liver tissue and thus if this technique would have potential for further implementation into surgical instruments or radiological intervention tools. METHODS: A miniaturized optical needle was developed able to collect DRS spectra between 500 and 1600 nm. Liver specimen of 24 patients operated for colorectal liver metastases were analyzed with DRS immediately after resection. Multiple measurements were performed and DRS results were compared to the histology analysis of the measurement locations. In addition, normal liver tissue was scored for the presence or absence of steatosis. RESULTS: A total of 780 out of the 828 optical measurements were correctly classified into either normal or tumor tissue. The resulting sensitivity and specificity were both 94%. The results of the analysis for each patient individually showed an accuracy of 100%. The Spearman's rank correlation of DRS-estimated percentages of hepatic steatosis in liver tissue compared to that of the pathologist was 0.86. CONCLUSIONS: DRS demonstrates a high accuracy in discriminating normal liver tissue from colorectal liver metastases. DRS can also predict the degree of hepatic steatosis with high accuracy. The technique, here demonstrated in a needle like probe, may as such be incorporated into surgical tools for optical guided surgery or percutaneous needles for radiological interventions.
  European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 09/2012; · 2.56 Impact Factor
• Article: Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy.

  B B Koolen, M J T F D Vrancken Peeters, J Wesseling, E H Lips, W V Vogel, T S Aukema, E van Werkhoven, K G A Gilhuijs, S Rodenhuis, E J Th Rutgers, R A Valdés Olmos
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  ABSTRACT: PURPOSE: The aim of this study was to evaluate the association of primary tumour (18)F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. METHODS: PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV(max)). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. RESULTS: In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV(max) was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV(max). CONCLUSION: Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT.
  European Journal of Nuclear Medicine 08/2012; · 4.53 Impact Factor