Biomedical subjects

J Jacquemier

Publications and source records attributed to J Jacquemier.

At least 19 recordsLinked to original sources

PubMed2006

Contribution of surgery in patients with bulky residual disease after chemoradiation for advanced cervical carcinoma.

AIM: To report the outcome of 30 patients who underwent surgery after concomitant chemoradiation for locally advanced cervical cancer with residual disease > or = 2 cm. METHODS: From 1988 to 2004, 143 patients with FIGO stage IB2-IVA cervical cancer underwent surgery after concurrent chemoradiotherapy. Among them, 30 had a residual cervical tumour > or = 2 cm prior to surgery. Surgery consisted in a simple or radical hysterectomy (n=15) or in a pelvic exenteration (n=15). Endpoints were recurrence and distant metastasis rates, overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Analysis included FIGO stage, response to chemoradiation, para-aortic lymphatic status or type of surgery: palliative (remaining disease after surgery) or curative (no evidence of remaining disease after surgery). RESULTS: Surgery has been only palliative in 11 cases. Pelvic recurrences occurred in 8 patients after a median interval of 8.8 months. Distant metastases occurred in 8 patients after a median interval of 13 months. So far, 16 patients have died (53.3%). The 3-year and 5-year OS rates are 64.9% and 55.6%, respectively, for the 19 patients who had a curative surgery. The DFS rate is 50.8% at 3 and 5 years in this latter group. Overall 12 patients (40%) are alive and free of disease after a median follow-up of 32.5 months. CONCLUSIONS: Adjuvant surgery may improve the outcome of patients with bulky residual tumour after chemoradiation for locally advanced cervical cancer, allowing a 5-year OS of 55.6% after curative intervention.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[Surgical resection after chemotherapy for advanced cervical carcinoma].

Standard treatment of locally advanced cervical carcinoma is actually represented by concomitant chemoradiotherapy followed by brachytherapy since several randomised study results in 1999. Surgical resection after concomitant chemoradiotherapy for locally advanced cervical carcinoma is discussed without evidence of benefice on survival and because morbidity. The aim of this study is to discuss surgery after chemoradiotherapy in terms of rate of morbidity and residual tumor, rate of pelvic disease control, overall survival and disease-free survival.

Brachytherapy↗

PubMed2006

Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer.

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.

Acid Anhydride Hydrolases↗

PubMed2006

[Pelvic posterior exenteration with immediate colo-rectal anastomosis: is it justified and feasible in advanced stage ovarian carcinoma?].

PURPOSE: The aim of this study is to show that the removal of the rectum is not an obstacle to implement an optimal surgery in advanced epithelial cancer of the ovary. MATERIAL AND METHODS: Retrospective study on a population of 44 women with advanced epithelial cancer of the ovary. The surgery was realized between January 95 and July 03, and all surgeries required a posterior exenteration. This treatment was completed by chemotherapy for 36 of them. RESULTS: The median survival of this population is 36.6 months. 6/44 patients (13.6%) had post-operative complications. The completion of chemotherapy started after an average of 5.2 weeks after surgery. All the assessable patients (43/44) have an anal satisfactory continence. CONCLUSION: The posterior exenteration, when it's necessary, for advanced epithelial cancer of the ovary must not be an obstacle to obtain an optimal surgery. Anal continence is respected and there are no more complications. This surgical act is safe for the management of this pathology without delaying the others therapeutics and allowing a satisfactory quality of life.

Adenocarcinoma↗

PubMed2006

Gene expression profiling of breast cell lines identifies potential new basal markers.

A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published 'intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management.

Biomarkers, Tumor↗

PubMed2006

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy.

A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; P<0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.

Adult↗

PubMed2004

Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Breast Neoplasms↗

PubMed2004

[Interest of sentinel lymph node biopsy for the staging of ductal carcinoma in situ].

PURPOSE: The aim of this study was to define the interest of sentinel lymph node biopsy (SLNB) for the staging of ductal carcinoma in situ (DCIS) and DCIS with micro-invasion (DCISM) in patients with breast carcinoma. MATERIAL AND METHODS: From June 1999 to December 2002 we listed, in a retrospective study, 52 patients treated surgically for a DCIS or a DCISM. All except one had an histology before surgery, and all had SLNB. Intraoperative imprint cytology of the sentinel lymph node (SLN) was performed then there were analysed by staining with hematoxylin-eosin. Patients with positive SLN underwent complete axillary dissection. RESULTS: It was removed an average of three SLNs by patient (extreme 1 to 6). Metastases in the SLN were detected in four (7,7%) of the 52 patients, including three cases had only micrometastases in the SLN. In the four patients treated with complete axillary dissection, the SLN were the only positives nodes. CONCLUSION: The SLNB for DCIS and DCISM increases the involvement rate of lymph node. Because of the widespread for early detection of breast cancer, it is noted a regular increase in the rate of DCIS. Even if the attitude to be had towards the lymph node metastases in these cases is not yet well defined, and so only 2% of the patients approximately die of this pathology, it is interesting because of increase in absolute value of mortality, to try to improve the prognosis criteria to modify the treatment of this pathology.

Breast Neoplasms↗

PubMed2004

Patients' and surgeons' perspectives on axillary surgery for breast cancer.

AIMS: The objectives of this study were to compare the postoperative morbidity of Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) and to compare the views of surgeons and patients regarding postoperative morbidity. METHODS: A prospective and comparative study was initiated to evaluate, 1 year after surgery, morbidity and sequelae after SLNB in 231 patients. Group I (n=141) underwent SLNB without ALND, group II (n=90) underwent SLNB followed by ALND when SLN where involved. Morbidity analysis was performed, respectively, by surgeons and patients. RESULTS: One hundred and eighty-five patients (80.5%) completed the questionnaire including 113 with SLNB alone, and 72 with ALND. One year after surgery, SLNB produced less morbidity than ALND for symptoms and function. There were significantly different assessments between surgeons and patients for pain, arm mobility and sensitiveness. CONCLUSIONS: One-year postoperative morbidity after SLNB is significantly lower than after ALND but views of surgeons and patients appears to be significantly different. Additional data are required to assess late consequences of axillary surgery.

Adult↗

PubMed2004

Multivariate analysis of survival in inflammatory breast cancer: impact of intensity of chemotherapy in multimodality treatment.

The prognosis of inflammatory breast cancer (IBC) is poor. We evaluated clinical and biopathological characteristics that could affect survival in 74 women with nonmetastatic IBC consecutively treated in our institution between 1976 and 2000. Patients received primary anthracycline-based chemotherapy at conventional doses (n=20) or high-dose chemotherapy (HDC) with haematopoietic stem cell support (HSCS) (n=54). After chemotherapy, 84% of patients underwent mastectomy, 95% were given radiotherapy and 55% tamoxifen. Immunohistochemistry data (ER, PR, ERBB2, P53) on pre-chemotherapy specimens suggested strong differences between IBC and non-IBC. The rate of pathological complete response to chemotherapy was 26% (27% with HDC and 17% with conventional doses, not significant). No single factor was found predictive of response. With a median follow-up of 48 months after diagnosis, the 5-year projected disease-free survival (DFS) was 24% and overall survival (OS) 41%. In multivariate analysis, the strongest independent prognostic factor was the delivery of HDC. The 5-year DFS and OS of patients were respectively 28 and 50% with HDC and 15 and 18% with conventional chemotherapy. These results and comparisons with other series of patients suggest a role for HDC with HSCS as part of the therapeutic approach in IBC. Further prospective studies are required to confirm it.

Adult↗

PubMed2004

Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Biomarkers, Tumor↗

PubMed2003

Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign.

It is thought that the risk of atypical hyperplasia (AH) increases with age, particularly among postmenopausal women. Three hypotheses were investigated to try to explain this phenomena: use of hormone replacement therapy (HRT), increased breast cancer screening and improvements in radiological quality. Data were collected from the Bouches du Rhône breast cancer screening programme database and from the pathological registry of all women operated on for breast diseases in the district. The AH incidence rate was studied using a Poisson regression analysis. The change in the profile of breast diseases was explored through studying changes in the proportion of AH among benign lesions and malignant diseases. The AH incidence rate significantly increased over time (13.6% per year). The proportion of AH among the benign diseases increased with time and was significantly higher for HRT users (Odds Ratio (OR)=2.05; 95% Confidence Interval (CI): 1.43-2.93). While AH decreased with age among HRT non-users, it increased among users as a proportion of both benign and malignant lesions. The AH incidence rate significantly increased among pre- and postmenopausal women. Our study suggests that this increase is partly explained by the incidental discovery of these lesions by mammography and partly by a real increase of the disease among HRT users.

Aged↗

PubMed2003

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

Breast Neoplasms↗

PubMed2003

Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy.

The purpose of this study was to evaluate the presence of micrometastatic cells in the apheresis products from patients with breast cancer, and also to determine if repeated infusion of contaminated products had any clinical impact. A total of 94 patients with high-risk breast cancer were enrolled in a prospective single center study to evaluate the use of dose-intensified chemotherapy (doxorubicine 75 mg/m(2) and cyclophosphamide 3000 or 6000 mg/m(2) for four cycles) with repeated (x 2) stem cell reinfusion. All women were monitored for the presence of metastatic cells in aphereses, collected after first course of intensive chemotherapy, and following additional mobilization with rhG-CSF. Epithelial cells were screened with monoclonal antibodies directed to cytokeratin. Eight of the 94 patients had detectable tumor cells in one or several aphereses collected after intensive chemotherapy; this was unrelated to other tumor characteristics, including size, histology, Scarff Bloom and Richardson (SBR) grading (presence or absence of hormone receptors). Hemato-poietic reconstitution was similar in the cells from these eight patients, and in the total patient population. Three of these eight patients relapsed. This study has confirmed that contamination of apheresis products remains a rare event, which does not seem to affect clinical evolution, even when reinfused into the patient.

Adult↗

PubMed2003

Calibration of immunohistochemistry for assessment of HER2 in breast cancer: results of the French multicentre GEFPICS study.

AIMS: HER2 protein is over-expressed in 15-30% of breast carcinomas. Immunohistochemistry (IHC) is a common and inexpensive method able to specifically detect HER2 protein. However, lack of standardization of IHC has been considered responsible for discrepancies in HER2 status assessment performed by IHC and fluorescence in-situ hybridization (FISH). This prompted us to perform a multicentric IHC calibration test to achieve a maximum accuracy of HER2-IHC compared with HER2-FISH taken as the reference method. METHODS AND RESULTS: Twelve French laboratories participated in this study, including 119 cases of invasive breast carcinomas for which both fixed and frozen tissues were available. HER2 expression was determined in fixed tissues by individual in-house IHC techniques, using either CB11 (Novocastra, Newcastle, UK) or A0485 (Dako, Glostrup, Denmark) anti-HER2 antibodies. Two cut-off values were used: 10% and 60% of immunostained cells. In 116 of the 119 cases, HER2 gene status could also be determined by FISH on frozen sections, performed in a single laboratory. Results were centralized and compared. When suboptimal concordance between IHC and FISH was observed, IHC was calibrated and a second run was performed. The specificity, sensitivity and accuracy of IHC compared with FISH were noted before and after calibration. Forty-four out of 116 (38%) tumours showed HER2 gene amplification. Accuracy of IHC was complete in the first run for 6/12 laboratories. Calibration, necessary for the six others, relied mainly on the combination of a heat-induced epitope retrieval step with an increase of dilution of the primary antibody. In the second run, HER2 over-expression was found in 46 (40%) and 44 (38%) of the 116 cases, using 10% or 60% of stained cells as cut-offs, respectively. The corresponding accuracy rates were 93% and 95%. CONCLUSIONS: This study showed that a high accuracy of IHC could be obtained for the determination of HER2 status in all laboratories using their in-house IHC technique, provided that a calibration process was performed. Antigen retrieval procedure, high dilutions of anti-HER2 antibody and the use of specific controls were crucial for HER2-IHC calibration. A 95% accuracy rate of IHC, using FISH as gold standard, was obtained by considering immunolabelling HER2-IHC results as a continuous variable, and taking 60% invasive stained cells as the cut-off for HER2 over-expression.

Adenocarcinoma↗

PubMed2003

[HER2 gene amplification assay: is CISH an alternative to FISH?].

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

Breast Neoplasms↗

PubMed2002

Overexpression of erb B2 remains a major risk factor in non-metastatic breast cancers treated with high-dose alkylating agents and autologous stem cell transplantation.

The importance of dose intensity has been strongly emphasized in high-risk breast cancer. Overexpression of erb B2 is clearly correlated with an overall poor prognosis which could be limited in patients receiving intensive chemotherapy with alkylating agents and autologous stem cell transplants (SST). Thirty-five patients with high-risk non-metastatic breast cancer (>4 involved lymph nodes), treated with high-dose chemotherapy (HDC) followed by SST were analyzed. All were previously treated by four cycles of standard-dose anthracycline or anthracene dione. Nine had erb B2 overexpression. Minimum follow-up duration was 41 months (median 68 months). At 5 years, the actuarial relapse-free survival is 57.4% and actuarial overall survival 67.4%. Patients with overexpression of erb B2 had significantly lower disease-free survivals (P: 0.021) and overall survivals (P: 0.001). On multivariate analysis, erb B2 overexpression appeared to be the single independent poor prognosis factor for relapse (RR 3.25, range 1.12 to 9.45) and overall (RR 5.28, range 1.74 to 16.03) survival. These results suggest that poor prognosis of erb B2 overexpression is unchanged after HDC with alkylating agents but a possible benefit may exist in these patients with the additional monoclonal antibody, herceptin.

Antineoplastic Agents, Alkylating↗

PubMed2002

Does a better grade of tumour occurring in women under hormone replacement therapy compensate for their lower probability of detection by screening mammography.

OBJECTIVE: To compare the prognostic factor of breast cancer survival between breast cancer diagnosed in subjects receiving hormone replacement therapy (HRT) before diagnosis to those without such a therapy. SUBJECTS AND METHODS: All breast cancers diagnosed between 1993 and 2000 within the breast cancer screening programme in Bouches du Rhône (France) were analysed for size, node status, and grade according to use, or not, of HRT. Univariate and multivariate analyses were carried out taking into account age, density of the breast, and mode of detection. RESULTS: The breast tumours diagnosed among HRT users had a lower grade whatever the mode of detection. The proportion of node positive tumours was identical in the two groups after adjustment for age. The smaller size of the tumours among HRT users is partly explained by the lower grade of these tumours Conclusion: Although tumours occurring in HRT users have a lower chance of being detected by screening, their prognostic factors, especially the grade of the tumour, are better than in non-users. More work is needed to find which part of this advantage is attributable to better surveillance of women treated with HRT

Aged↗