Papers by R. Van Den Broecke
Strahlentherapie und Onkologie, 2012
Gunaikeia, 2004
Casteels, M. Christiaens, Marie-Rose Berlière, M. Berteloot, Patrick Cocquyt, V. De Greve, J. De ... more Casteels, M. Christiaens, Marie-Rose Berlière, M. Berteloot, Patrick Cocquyt, V. De Greve, J. De Nys, Katelijne Dumortier, P. Geelhand, M. Kerger, J. Kirkove, C. Lifrange, E. Lobelle, JP Machiels, JP Maréchal, M. Neven, Patrick Paridaens, Robert Piccart, M. Quataert, M. ...
The aim of this article is to highlight the recent changes in the surgical approach of the axilla... more The aim of this article is to highlight the recent changes in the surgical approach of the axilla in breast cancer patients. Axillary staging is dominated by the sentinel lymph node (SLN) biopsy, which is now widely practiced in clinically node negative patients. Most authors believe a SLN biopsy may even be performed in patients with a large or multifocal tumour, before neo-adjuvant systemic therapy, during pregnancy, after prior excisional biopsy and after prior mantle field radiotherapy of the breast. Intra-operative assessment of the SLN is recommended as it can identify half of all positive lymph nodes. It is generally accepted that it is safe to omit an axillary lymph node dissection (ALND) in patients with a negative SLN or with only isolated tumour cells (<0.2 mm) in the SLN. Moreover, in a subset of patients with a micro-/macrometastasis in the SLN it might not be necessary to perform a completion of ALND. We suggest to accept the option of omitting completion of ALND in...
background: Ovarian tissue (OT) cryopreservation and transplantation are options for fertility pr... more background: Ovarian tissue (OT) cryopreservation and transplantation are options for fertility preservation in young female cancer patients. methods: We investigated xenotransplantation of human OT into back muscle (B) of severe combined immunodeficiency mice. OT follicle content was evaluated by stereomicroscopy and pre-transplantation. Xenograft survival, follicular development (with/without FSH administration), apoptosis and vascularization were compared in B-versus K-site (under the kidney capsule) several times after grafting using histology, immunohistochemistry and magnetic resonance imaging. In vitro maturation (IVM) was also performed. results: Anastomoses which developed from existing human and invading murine vessels were seen in OT at both sites, but angiogenesis was more prominent at the B-than K-site (P , 0.001). Vascularization and follicle size were correlated in the B-group (Spearman's coefficient 0.73; P , 0.001). FSH increased early (8 days) micro-vessel formation in B but not in K grafts (P , 0.0001, versus no FSH). B-site grafts showed a better histological morphology and survival (P ¼ 0.0084), formation of larger antral follicles (P ¼ 0.005), more metaphase-II (MII) oocytes, growing follicles (P ¼ 0.028) and slightly fewer apoptotic follicles than K grafts. One MI oocyte from B underwent IVM and reached MII stage next day. conclusions: To our knowledge, this is the first report of MII and IVM-MII oocytes obtained from B xenografts. We report the largest oval-shaped antral follicles containing an MII oocyte obtained after OT xenotransplantation to date. Xenografting in the mouse B should be further explored as a method for human OT transplantation.
Cancer Research, 2019
Positive surgical margins represent a high risk for adverse clinical outcome in breast conserving... more Positive surgical margins represent a high risk for adverse clinical outcome in breast conserving surgery (BCS). Therefore, the goal of BCS is to avoid positive margins and hence avoid reoperation. Unfortunately, most studies currently assess the rate of positive resection margins at 20%. This is in part due to the lack of a time- and cost-effective method for intraoperative margin assessment, which would enable the prediction of positive margins during the initial surgery. We propose to address this problem by performing intraoperative high-resolution 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) with X-ray computed tomography (CT). This method relies on the high sensitivity of FDG-PET for detecting metabolically active tumor tissue, and the delineation of the anatomical margins of the specimen using CT. In this proof-of-concept study we assess the feasibility of this technique. Twenty patients with breast cancer that were eligible to undergo BCS were enrolled in...
European Journal of Surgical Oncology, 2019
Background: Body composition has emerged as an important prognostic factor in cancer patients. Sa... more Background: Body composition has emerged as an important prognostic factor in cancer patients. Sarcopenia and sarcopenic obesity (obesity with depleted muscle mass) might be predictive of morbidity and mortality in advanced breast cancer and also of toxicity to chemotherapy. We retrospectively studied patients with advanced breast cancer receiving adjuvant chemotherapy in order to determine if sarcopenia was associated with a higher incidence of toxicity and a shorter time to tumor progression.
Annals of Oncology, 2014
ABSTRACT Aim: Despite the results of large randomized trials in the UK and Canada showing that hy... more ABSTRACT Aim: Despite the results of large randomized trials in the UK and Canada showing that hypofractionation (HF) radiotherapy is at least as favorable as normofractionation (NF) schemes for whole-breast irradiation (WBI) in terms of loco-regional control and cosmetic outcome, some radiation oncologists are reluctant to use HF WBI fearing increased toxicity, especially in large breasted patients. In this study the effect of the fractionation schedule on acute toxicity was investigated in a cohort of 229 breast cancer patients with various cup sizes treated with WBI in 2 different radiotherapy centers. Methods: From May 2010 till December 2012, 150 patients from Ghent University Hospital (GUH) and 79 patients from Clinique et Maternite Sainte-Elisabeth Namur (CMSE) were included in a prospective study aiming at developing a prediction model for radiation-related breast toxicity using clinical, dosimetric and genetic parameters. All patients at GUH were treated with a HF scheme of 40,05 Gy in 15 fractions. At CMSE patients with a cup size D or more were treated with NF WBI (50 Gy in 25 fractions), while patients with a cup size Results: Patients with a cup size Conclusions: HF whole-breast radiotherapy results in significantly less moist desquamation compared to NF regardless of cup size. Disclosure: All authors have declared no conflicts of interest.
Acta Chirurgica Belgica, 2008
In the staging of early breast cancer a positive sentinel node biopsy is followed by axillary dis... more In the staging of early breast cancer a positive sentinel node biopsy is followed by axillary dissection in order to assess the number of metastasised lymph nodes. Immediate axillary dissection has been abandoned in our centre. If necessary, an axillary dissection takes place about two weeks later, but the post surgical inflammatory reaction might hinder dissection and decrease the number of removed lymph nodes. In a retrospective study, the total number of lymph nodes removed by sentinel node biopsy followed later by axillary dissection (n = 53) was compared with the total number of lymph nodes removed by axillary dissection without previous sentinel node biopsy in combination with breast conserving therapy (n = 113), or following breast conserving therapy (n = 15), or in combination with mastectomy (n = 65). A total number of 12 (median) lymph nodes were removed by sentinel node biopsy followed later by axillary dissection. Only in the mastectomy + axillary dissection group were less lymph nodes (median of 9) removed (P = 0.009). Multiple regression showed the total number of axillary lymph nodes to be correlated with age (R = -0.21; P = 0.002) and with the number of lymph nodes with metastasis (R = 0.31; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Age distribution showed that the mastectomy + axillary dissection group had the oldest patient population. The number of removed axillary lymph nodes is not decreased by preceding sentinel node biopsy, but depends on other factors.
Acta Chirurgica Belgica, 2007
Oestrogens have a broad spectrum of physiological functions, ranging from regulation of the menst... more Oestrogens have a broad spectrum of physiological functions, ranging from regulation of the menstrual cycle and reproduction to the modulation of bone, brain and lipid metabolism. Oestrogens also play an important role in breast carcinogenesis (1). From epidemiological studies, we know that total oestrogen exposure increases a woman’s risk of developing breast cancer. Oestrogens have been associated with breast cancer initiation and promotion. They and other female steroid hormones like progesterone, stimulate breast epithelial cell proliferation, which facilitates mutation and the likelihood of carcinogenic events. This results in a modulating role on tumour growth, developmental progression, invasion and metastasis (1). Oestrogens bind to specific intracellular receptors, oestrogen receptor (ER)a and ERb. There are multiple signal transduction pathways involving the ER. The activated ER mainly functions as a nuclear transcription factor. The complex binds directly to DNA target genes through oestrogen response elements (ERE). Oestrogen related genes can also be transcribed without an ERE as the oestrogen-ER complex can also bind to other transcription factors or genomic units and proteins (AP1, SP1, nuclear factor kB). Oestrogens can also bind to ERs located in or near the plasma membrane activating several growth factor signalling pathways. Over 80% of all breast cancers express ER. The last five decades have brought a variety of modalities that can intervene in oestrogen-mediated cell signalling. Selective Oestrogen Receptor Modulators (SERMs) interfere in the binding of oestrogens to the ER. SERMs are unique and very attractive. They antagonise oestrogens in some tissues – as in the breast, whereas they mimic oestrogens in others to prevent ageing – as in postmenopausal bone and heart. The mechanisms for tissue selectivity of SERMs are complex and not completely known. One of many is that different ligands induce different three-dimensional structures within the ligand-binding domain of the receptor leading to the exposure of different surfaces to the nuclear receptor co-activators or repressors. The balance of co-repressors and co-activators influences the transcriptional activity of the SERM activated ER. A better understanding of tissue specificity of SERMs will probably lead to the development of the ideal compound. SERMs now already differ between each other regarding their stimulatory effect on the uterus. The side effect of SERMs on the thrombo-embolic and vasomotor system is considered as a class effect (2). Although there are naturally occurring SERMs, most of our knowledge comes from chemically designed compounds. First-generation SERMs, tamoxifen and toremifene, are based on a nonsteroidal triphenylethylene structure. Raloxifene and arzoxifene are benzothiophenes and respectively called second and third generation SERMs. Other SERMs are the naphthalenes (4 generation, lasophoxifene) and many other compounds being studied like TSE-424, SP500263, ERA-923 and EM-652 (acolbifene). Tamoxifen has been a pioneering drug in the targeted treatment of breast cancer for about 30 years, and worldwide the most prescribed SERM. In 2002, all patents had expired and tamoxifen became available as a generic drug. It is successfully used to treat patients with all stages of hormone-responsive breast cancer. Tamoxifen arrests cells in the early G1-phase of the cell cycle. In metastatic ER breast cancer, agents like tamoxifen and toremifene are able to stop tumour growth in over 50% of women. However, almost all women who initially respond to therapy eventually relapse with resistant disease. In early stage disease, after surgical removal of the tumour, adjuvant tamoxifen protects remaining breast tissue, the other breast and distant organs from becoming involved with breast cancer metastases. This increases breast cancer survival. The Early Breast Cancer Trialists Collaborative Group (EBCTCG) has, since 1984, collected all available data on randomized trials of therapy for early breast cancer. The most recent publication reviewed the 15-year effects of adjuvant chemotherapy and hormonal therapy confirming this survival benefit of tamoxifen (3). Tamoxifen also has a promising role in the prevention of ER breast cancer in healthy ‘atrisk’ women with a long carry-over effect (4, 5). Unfortunately, long-term use of tamoxifen and toremifene in postmenopausal women is associated with Tamoxifen or Aromatase Inhibitors in Breast Cancer : Efficacy and Safety
European journal of gynaecological oncology, 2005
Primary non Hodgkin's lymphoma (NHL) of the cervix and vagina is uncommon; the incidence of u... more Primary non Hodgkin's lymphoma (NHL) of the cervix and vagina is uncommon; the incidence of uterine lymphoma is estimated to be less than 0.5% of all NHL. Patients regularly present with vaginal bleeding. The diagnosis is made on biopsy but this can be difficult on small samples which may not be representative of the lesion. Immunohistochemical analysis and often molecular techniques are required to confirm the diagnosis. We report two cases of primary diffuse large B-cell lymphoma of the cervix. In the first case, the diagnosis could only be made on repeat biopsies. The second case presented as a cervical polyp. Gynecologists should be aware of this rare clinical entity in order to apply the proper treatment.
Journal of Clinical Pathology, 2010
AimsA few reports have assessed HER2 status in breast cancer by both dual-probe fluorescence in s... more AimsA few reports have assessed HER2 status in breast cancer by both dual-probe fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in an unselected and consecutive fashion, but CEP17 andHER2copy number were not evaluated separately in these studies. Therefore, the aim of this study was to perform FISH testing forHER2in a large number of breast tumours, irrespective of the IHC scores, which were also determined in all cases.MethodsBoth FISH and IHC were applied to 200 tumours from 196 consecutive patients who underwent resection of primary breast cancer with the sentinel procedure and/or axillary dissection. Not only the ratio, but also meanHER2and CEP17 copy number were determined and used in statistical analyses to evaluate relationships between FISH, IHC and clinicopathological features.ResultsThe amplification status based solely on HER2 signals was 98% concordant with results of dual-probe FISH. In non-amplified tumours, the mean CEP17 andHER2copy number co...
Gynecologic Oncology, 2006
Background: Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract, which ... more Background: Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract, which originates from mesonephric duct remnants. Its diagnosis is pathologically challenging, because MNAC may exhibit a mixture of morphological patterns that complicates the differential diagnosis. Case presentation: The patient in this case was a 48-year-old woman with a polypoid mass protruding into the endocervical canal. The patient underwent a total hysterectomy outside the institution. During biopsy, the mass showed a cerebroid aspect. Histological study revealed a tumor with a predominantly tubular and ductal growth pattern. The immunoprofile showed negative staining for calretinin, carcinoembryonic antigen (CEAm), estrogen receptors (ER), and progesterone receptors (PR), and positive staining for CD10, p16, and PAX2. The Ki-67 score was 46%. Using a next-generation sequencing assay, we documented genomic alterations in KRAS and CTNNB1, low tumor mutation burden (TMB), and an absence of microsatellite instability. In addition, gain of the long arm of chromosome 1 (1q) was also documented using chomogenic in situ hybridization (CISH). Three years later, the patient presented pulmonary nodules in the lingula and left basal lobe that were resected by thoracotomy. The histopathologic study of the pulmonary nodules confirmed the presence of metastases. Conclusion: Carcinomas of mesonephric origin are among the rarest subtypes of cervical tumors. We report the first case of mesonephric adenocarcinoma of the cervix with lung metastases showing a CTNNB1 gene mutation.
Cancer Research, 2009
Background: Vesicle exocytosis, controlled by secretory GTPases such as Rab27B, delivers critical... more Background: Vesicle exocytosis, controlled by secretory GTPases such as Rab27B, delivers critical pro-invasive factors into the tumor microenvironment. The biological role and expression status of Rab27B in breast cancer was unknown.Methods: Rab27B was studied in human breast cancer cells (MCF-7, T47D, ZR75.1) using GFP-fusion constructs, including Rab27A and Rab27B point mutants defective in GTP-binding or geranylgeranylation. In cell culture, cell-cycle progression was evaluated by flow cytometry and Western blotting, invasion was assessed using Matrigel and collagen type I substrates. Orthotopic tumor growth, local invasion and metastasis were analyzed in mouse xenograft models. Mass spectrometry was performed to identify Rab27B-secreted pro-invasive factors. Rab27B levels in clinical breast cancer were analyzed by quantitative reverse transcription-polymerase chain reaction (n=20) and immunohistochemistry (n=60). Statistical tests were two-sided.Results: Rab27B-upregulation prom...
Biology of Reproduction, 2001
The objectives of the present study were to achieve 1) oocyte maturation, 2) oocyte competence of... more The objectives of the present study were to achieve 1) oocyte maturation, 2) oocyte competence of fertilization, and 3) oocyte competence of embryogenesis with oocytes from primordial follicles obtained from cryopreserved newborn mouse ovaries by using a two-step method. In the first step, frozen-thawed newborn mouse ovaries were transplanted under the kidney capsule of recipients for the initiation of growth from the primordial follicle stage on. In the second step, growing preantral follicles in the ovarian grafts were recovered and cultured. The results demonstrated that primordial follicles were able to be recruited to preantral follicles during the period of transplantation, and preantral follicles could be mechanically isolated from ovarian grafts. Under the present in vitro culture conditions, 85.8% of the isolated follicles (n ؍ 332) from ovarian grafts survived the 12-day in vitro culture process, 84.9% of the recovered oocytes (n ؍ 285) were germinal vesicle breakdown (GVBD)-competent, and 76% of the oocytes that underwent GVBD (n ؍ 242) developed to the metaphase II (MII) stage. In the in vitro fertilization experiments, 75.4% of 142 inseminated MII oocytes underwent fertilization and cleavage to the 2-cell stage. Subsequently, 79.7% of the 2-cell-stage embryos (n ؍ 69) progressed to the late morula-early blastocyst stage. Transfer of late morulaearly blastocyst embryos resulted in the production of live offspring. From our experiments, it may be concluded that in vivo maturation by grafting followed by in vitro maturation of frozenthawed primordial follicles can restore fertility in mice. This model could be useful for a similar application in the human.
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Papers by R. Van Den Broecke