Breast Clinic

Leuven, Belgium

Breast Clinic

Leuven, Belgium
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Coleman R.,Academic Unit of Clinical Oncology | De Boer R.,Royal Melbourne and Western Hospitals | Eidtmann H.,Universitats Frauenklinik Kiel | Llombart A.,Institute Oncologica | And 12 more authors.
Annals of Oncology | Year: 2013

Background: Aromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer. Although generally more effective than tamoxifen, aromatase inhibitor therapy is associated with increased bone loss and fracture risk. Patients and methods: Postmenopausal women receiving adjuvant letrozole (2.5 mg/day for 5 years; N = 1065) were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every 6 months for 5 years, or delayed zoledronate (initiated for fracture or on-study bone mineral density [BMD] decrease). The primary end point was the change in lumbar spine BMD at 12 months. Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival (DFS), and overall survival were assessed as secondary end points. Results: At 60 months (final analysis), the mean change in lumbar spine BMD was +4.3% with immediate zoledronate and -5.4% with delayed intervention (P < 0.0001). Immediate zoledronate reduced the risk of DFS events by 34% (hazard ratio [HR] = 0.66; P = 0.0375) with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate. In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR = 0.46; P = 0.0334). Conclusions: Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone. Clinical Trials Registration No: NCT00171340. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Adriaenssens N.,Breast Clinic | Adriaenssens N.,Vrije Universiteit Brussel | Vinh-hung V.,University of Geneva | Vinh-hung V.,Oncology Center | And 9 more authors.
Breast Cancer: Basic and Clinical Research | Year: 2012

Introduction: Shoulder/arm morbidity is a common complication of breast cancer surgery and radiotherapy (RT), but little is known about acute contralateral morbidity. Methods: Patients were 118 women enrolled in a RT trial. Arm volume and shoulder mobility were assessed before and 1-3 months after RT. Correlations and linear regression were used to analyze changes affecting ipsilateral and contralateral arms, and changes affecting relative interlimb differences (RID). Results: Changes affecting one limb correlated with changes affecting the other limb. Arm volume between the two limbs correlated (R = 0.57). Risk factors were weight increase and axillary dissection. Contralateral and ipsilateral loss of abduction strongly correlated (R = 0.78). Changes of combined RID exceeding 10% affected the ipsilateral limb in 25% of patients, and the contralateral limb in 18%. Aromatase inhibitor therapy was significantly associated with contralateral loss of abduction. Conclusions: High incidence of early contralateral arm morbidity warrants further investigations. © the author(s), publisher and licensee Libertas Academica Ltd.


De Leeneer K.,Ghent University | Coene I.,Ghent University | Crombez B.,Ghent University | Simkens J.,Ghent University | And 7 more authors.
Breast Cancer Research and Treatment | Year: 2012

In order to adequately evaluate the clinical relevance of genetic testing in sporadic breast and ovarian cancer patients, we offered comprehensive BRCA1/2 mutation analysis in patients without a family history for the disease. We evaluated the complete coding and splice site regions of BRCA1/2 in 193 sporadic patients. In addition, a de novo mutation was further investigated with ultra deep sequencing and microsatellite marker analysis. In 17 patients (8.8%), a deleterious germline BRCA1/2 mutation was identified. The highest mutation detection ratio (3/7 = 42.9%) was obtained in sporadic patients diagnosed with breast and ovarian cancer after the age of 40. In 21 bilateral breast cancer patients, two mutations were identified (9.5%). Furthermore, 140 sporadic patients with unilateral breast cancer were investigated. Mutations were only identified in patients diagnosed with breast cancer before the age of 40 (12/128 = 9.4% vs. 0/12 with Dx > 40). No mutations were detected in 17 sporadic male breast cancer and 6 ovarian cancer patients. BRCA1 c.3494-3495delTT was identified in a patient diagnosed with breast and ovarian cancer at the age of 52 and 53, respectively, and was proven to have occurred de novo at the paternal allele. Our study shows that the mutation detection probability in specific patient subsets can be significant, therefore mutation analysis should be considered in sporadic patients. As a consequence, a family history for the disease and an early age of onset should not be used as the only criteria for mutation analysis of BRCA1/2. The relatively high mutation detection ratio suggests that the prevalence of BRCA1/2 may be underestimated, especially in sporadic patients who developed breast and ovarian cancer. In addition, although rare, the possibility of a de novo occurrence in a sporadic patient should be considered. © 2011 Springer Science+Business Media, LLC.


Adriaenssens N.,Oncology Center | Buyl R.,Vrije Universiteit Brussel | Lievens P.,Vrije Universiteit Brussel | Fontaine C.,Breast Clinic | Lamote J.,Oncological Surgery
Lymphology | Year: 2013

There is no consensus on the definition of Breast Cancer Related Lymphedema of the arm (BCRL) because there are no agreed standards in measurement methods and diagnostic criteria. The main objective of this study is to compare mobile infrared optoelectronic volumetry with a Perometer® with two commonly used methods for the evaluation of arm volume in patients with different degrees of BCRL. Bilateral arm volumes of eighty participants, with and without clinical BCRL, were calculated with a mobile Perometer®, by water displacement, and with circumferential measurements, integrated in the frustrum, single frustrum, and disc model method. The ICC of the Perometer® was between 0.997 and 0.999. The frustrum and disc model method produced the largest volume measurements and water displacement the smallest, while Perometer® measures were in between. On average, volume of the dominant arm was found to be 2.2% higher than the non-dominant arm in the healthy control group, cautioning for intra- patient differences between both arms when comparing ipsilateral to contralateral arm for the diagnosis of BCRL with a threshold value. Future research would likely benefit from the use of the Perometer® compared to the other arm volume evaluation tools for BCRL, and further, the single frustrum method should not be used for volume estimations of edematous arms.


Zamora V.,Gastroenterology Hospital C Bonorino Udaondo | Cabanne A.,Gastroenterology Hospital C Bonorino Udaondo | Salanova R.,Gastroenterology Hospital C Bonorino Udaondo | Bestani C.,Gastroenterology Hospital C Bonorino Udaondo | And 6 more authors.
Digestive and Liver Disease | Year: 2010

Introduction: Somatostatin receptors are expressed in a large number of human tumours. The somatostatin receptors types 1-5 expression in a series including 100 gastro-entero-pancreatic endocrine tumours were analysed. Methods: From a prospectively built database of patients with gastro-entero-pancreatic endocrine tumours referred from three institutions, 100 cases with clinical and pathological data were selected. Somatostatin receptors expression by immunohistochemistry with somatostatin receptor types 1-5 antibodies in tissue paraffin sections were studied and correlated with the histological diagnosis according to the WHO classification, location and functional status. Results: Of the 100 cases, 67 were gastrointestinal tumours, 25 pancreatic and 8 liver metastasis of unknown origin. Thirty-one of them were functioning tumours: 2 insulinomas, 5 gastrinomas, 1 glucagonoma and 23 carcinoids. Somatostatin receptors expression was observed in 94 tumours. The six negative cases were all non-functioning tumours. Somatostatin receptors 2a and 5 were highly expressed (86 and 62%, respectively), and surprisingly found even in poorly differentiated endocrine carcinomas. Somatostatin receptors expression was less frequent in pancreatic than in gastrointestinal tumours. Well-differentiated neoplasms had a higher density of somatostatin receptors. Only SSTR2a showed membrane staining. Conclusions: Immunohistochemistry revealed that somatostatin receptors were highly expressed in both primary and metastatic gastro-entero-pancreatic endocrine tumours with heterogeneous staining distribution. It proved to be a reliable technique even in small tumour samples. © 2009 Editrice Gastroenterologica Italiana S.r.l.


Isla Larrain M.T.,National University of La Plata | Colussi A.G.,National University of La Plata | Demichelis S.O.,University of Buenos Aires | Barbera A.,Breast Clinic | And 3 more authors.
International Journal of Biological Markers | Year: 2013

The aim of this study was to elucidate whether the IgG humoral immune response to breast cancer cells is directed to the aberrant mucin-1 (MUC1) associated to this type of cancer. To this aim, an adaptation of immunohistochemistry (IHC) was performed on samples of 45 breast cancer tissues, 12 benign disease tissues, and 31 normal tissues, incubated with matched serum samples from the same patients. Each serum sample was also incubated, with a modified immunocytochemistry (ICC), with MCF7 cells. In both techniques, serum was employed instead of the primary antibody. In the case of IHC, the reactivity with sera diminished when added after previous incubation of the tumor/tissue with an anti-MUC1 mAb; the reduction in reactivity was: from 93% to 44% in breast cancer tissues, and from 100% to 67% in benign disease tissues. The reactivity of normal samples (36%) remained unchanged. In the case of ICC, the reactivity with sera decreased after incubation with anti-MUC1 mAb from 71% to 16% in breast cancer tissues, from 83% to 0% in benign disease tissues, and from 52% to 10% in normal serum samples. These results were confirmed employing siRNA MUC1 transient gene knockdown. By Western blot analysis - after immunoprecipitation (IP) of the circulating MUC1- and ELISA, the TF antigen was detected in circulating MUC1 in all breast cancer and benign samples while Tn was detected in 38% of the samples. The existence of IgG autoantibodies against aberrantly glycosylated MUC1 may have a protective role and may contribute to a better prognosis in some patients. Enhancement of this natural immune response may constitute an alternative therapeutic strategy. © 2013 Wichtig Editore.


Isla Larrain M.T.,National University of La Plata | Rabassa M.E.,National University of La Plata | Lacunza E.,National University of La Plata | Barbera A.,Breast Clinic | And 3 more authors.
Tumor Biology | Year: 2014

Indoleamine-2,3-dioxygenase (IDO) has been established as a normal mechanism of peripheral tolerance and immunosuppression. Besides, malignant tumors release microvesicles (MV) related with tumor dissemination. The aims of this study were to determine the expression of IDO in breast cancer and circulating microvesicles from breast cancer patients and to perform an in silico analysis to find genes co-expressed to IDO. One hundred and twenty-two tissue and serum breast samples (91 malignant, 21 benign, and 10 normal), and MCF7, MDA-MB-231, and T47D breast cancer cell lines were included. Standard immunohistochemistry (IHC), immunocytochemistry (ICC), Western blot (WB), and RT-PCR were employed. Microvesicle isolation from plasma samples was obtained by serial centrifugation and ultracentrifugation. By IHC, 60 % breast cancer, 43 % benign, and 20 % normal samples were positive. Significant differences were found among normal, benign, and malignant samples. Breast cancer stages I, II, and III expressed IDO in 42, 66, and 71 % of samples, respectively, while breast cancer cell lines also reacted; by WB, 9/25 microvesicles fractions showed bands at 42 kD. In silico analysis of IDO 1 gene expression in breast cancer showed its association with several genes related to immune response and apoptosis. Moreover, IDO and co-expressed genes were found predominately in basal and erbB2 subtypes. The cumulative data indicate a high expression of IDO in breast cancer which increased with higher stages. Furthermore, IDO was found in association with circulating breast cancer MV, while experimental and in silico gene expression revealed that IDO was mainly expressed in a triple-negative subgroup. © 2014 International Society of Oncology and BioMarkers (ISOBM).


PubMed | Breast Clinic
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

22162 Background: c-erb-B2 is amplified in approximately 18-20% of breast cancers (BC). Her2 overexpression represents the determining factor for the potential use of trastuzumab. Immunohistochemistry (IHC) is the most used technique. Available evidence suggests that about 20% of current Her2 testing is inaccurate. There is no universal consensus about the technical aspects to be used in the definition of Her2 status. The objective was to evaluate the different results obtained by two groups of pathologists in the determination of Her2 and its impact in the therapeutic decision.Between June-December/07 64 clinical reports of pts with BC were analyzed. The original Her2 status analyzed by pathologists of group A was reviewed by a pathologist of reference (group B). For Her2 status review, IHC was used with a policlonal antibody (CB11-1/500), antigenic recovery, Diaminobenzidina (DAKO) and system of detection ENVISION. Manual method per protocol of work was used (National Plan Her2). The results were interpreted using score 0 to 3 +.64 biopsies were analyzed by group A. The determination of Her2 was score 0 in 2 pts (3,1%), score 1 in 38 (59,3%), score 2 in 16 (25%) and score 3 in 8 (12,5%). Later on, a review was performed by group B, 2 pts (3,1%) scored 0, 45 (70,3%) scored 1; 2 (3,1%) scored 2 and 15 (23,4%) scored 3. Of the 2 pts score 0 of group A, 1 pt turned out to be score 2 and the other score 3. After group B analysed those pts that for group A were score 1, the results were: 86% (33 pts) scored 1 and 14% (5 pts) scored 3. According to group A, 16 pts scored 2. Group B results were totally different: 10 pts turned out to be a score 1 and 6 score 3. Only 3 of the 8 pts score 3 for group A coincided with group B results. Of the remaining 5 pts, 2 scored 0, 2 scored 1 and 1 scored 2. Of 15 pts score 3 of group B, 5 were previously score 1, 6 score 2, 3 score 3 and 1 score 0. For group B, only 2 pts turned out to be score 2, that for group A have been score 3 and score 0.In our population of pts, the overexpression of Her2 score 3 determined by group B (23,4%) coincides with the results reported in the bibliography. Discrepancy exists in the determination of the Her2 between both groups of pathologists. The review of the biopsies increased the detection of Her2 score 3 of 12,5% to 23,4%. No significant financial relationships to disclose.


PubMed | Breast Clinic
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

20718 Background: HER-2/neu status of the breast cancer (BC) is determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Numerous reports have been published identifying discrepancies between IHC and FISH methods from different manufacturers, as well as tissue processing, reagent variability, antigen retrieval methods, scoring interpretation, tumor heterogeneity, and the semiquantitative nature of the test. The objective was to compare the results of HER-2 assessment by IHC and FISH in patients (pts) with BC being considered for trastuzumab therapy.For HER2 status review, IHC was used with a policlonal antibody (CB11-1/500), antigenic recovery, Diaminobenzidina (DAKO) and system of detection ENVISION (DAKO). Manual method per protocol of work was used (National Plan Her2). The results were interpreted using score 0 to 3+. FISH was used to assess HER-2 gene amplification. The tumors were tested in two reference centres. All procedures were applied to de-paraffinised tissue sections of BC samples.From July to December 2007, 42 cases of infiltrative BC were studied and correlation with HER-2 overexpression between IHC and FISH was determined. Three plus HER-2 overexpression was found in 9 pts (23%), 2+ in 8 (20%), 1+ in 3 (7,7%) and 0 in 19 (48,7%). In 3 cases this determination was not done. FISH was positive in 14 cases (33,3%) and negative in 28 (66,6%). Only 2/19 (10,5%) IHC score 0 were FISH positive. Four of 8 (50%) IHC 2+ were FISH positive and the other 4 were negative. Only 1 of the 9 IHC score 3+ was FISH negative, so the discordance in this case was 11,1%.We found a significant discordance in 3 cases. Two were IHC score 0 and FISH positive, and 1 was IHC score 3+ and FISH negative. In the 8 cases of IHC score 2+, FISH was used to define positivity: 4/8 (50%) were FISH positive. We suggest to carry out FISH to evaluate the status of HER-2 in BC, especially when is considering the use of trastuzumab therapy. No significant financial relationships to disclose.


PubMed | Breast Clinic
Type: | Journal: Breast cancer : basic and clinical research | Year: 2012

Shoulder/arm morbidity is a common complication of breast cancer surgery and radiotherapy (RT), but little is known about acute contralateral morbidity.Patients were 118 women enrolled in a RT trial. Arm volume and shoulder mobility were assessed before and 1-3 months after RT. Correlations and linear regression were used to analyze changes affecting ipsilateral and contralateral arms, and changes affecting relative interlimb differences (RID).Changes affecting one limb correlated with changes affecting the other limb. Arm volume between the two limbs correlated (R = 0.57). Risk factors were weight increase and axillary dissection. Contralateral and ipsilateral loss of abduction strongly correlated (R = 0.78). Changes of combined RID exceeding 10% affected the ipsilateral limb in 25% of patients, and the contralateral limb in 18%. Aromatase inhibitor therapy was significantly associated with contralateral loss of abduction.High incidence of early contralateral arm morbidity warrants further investigations.

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