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François Eisinger

Publications and source records attributed to François Eisinger.

At least 19 recordsLinked to original sources
PubMed2006

Patients' characteristics and rate of Internet use to obtain cancer information.

The aim of this study was to present baseline data on the access to Internet by French breast cancer patients attending genetic clinics and to examine factors affecting Internet health-related use. Twenty-four percent of participants used Internet to obtain information about the disease. This rate was higher among patients with health occupations [adjusted odds ratio (adjOR) 2.6; 95% confidence interval (CI) 1.3-5.1], the most highly educated (adjOR 2.1; 95% CI 1.1-4.0) and those under 41 years of age (adjOR 7.3; 95% CI 2.1-26.2). Almost one of every three women was dissatisfied of this source of information.

Adult↗
PubMed2006

Impact of an information booklet on satisfaction and decision-making about BRCA genetic testing.

The aim of this study was to assess the impact of a standardized patient information booklet on decisions women make about genetic testing. This French national multi-centre survey included all women with cancer to whom genetic testing for BRCA1/2 mutation had been proposed. The control group was surveyed before the booklet became available (n = 263), and the experimental group, after being given it personally (n = 297). After multivariate adjustment, the booklet had a positive impact on satisfaction with the information provided (Odds ratio (OR) = 2.9; 99% confidence interval (CI) = 1.7-5.0; P = 0.001), decreased the decisional conflicts due to lack of information (OR = 1.9; 99% CI = 1.1-3.3; P = 0.002), and had a marginal impact on knowledge (R2-gain = 3%; P = 0.001). The women in the experimental group decided more frequently to undergo testing (99% vs. 95%; P = 0.009). In addition to a consultation providing more tailored information, a standardized written document improved the decision-making process involved in giving informed consent to genetic testing.

Breast Neoplasms↗
PubMed2005

Typical medullary breast carcinomas have a basal/myoepithelial phenotype.

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-line mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n=44) and non-TMBC grade III with no or low scores (n=160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n=17) and non-MBC grade III cases (n=140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R=2.29), MIB1 > 50 (R=3.80), ERBB2 negativity (R=2.24) and p53 positivity (RR=1.45).

Breast Neoplasms↗
PubMed2005

[Breast cancer screening for women with a strong familial risk].

Screening for breast cancer in high-risk women could be seen through the general criteria for cancer screening. The attributable part of BRCA in breast cancer is estimated to be between 2 and 5%. For these women, breast cancer screening lay between prevention with low risk/benefit efficacy and prophylactic mastectomy with high efficacy but low acceptability. Risk reduction could be achieve with "classic" screening tools (examination, mammography and ultra sound) but should soon benefit from MRI experimental protocols. Later, combined imaging and biology protocols may solve the issue of screening in cancer prone women. A comprehensive program is required, taking in account both the competitive risk of ovarian cancer and the risk reduction observed at the breast level with prophylactic oophorectomy, at least in BRCA1 women. Information, and psychological help is all the more a necessity, since the lack of specificity of screening may induce harm, particularly for these women. Due to methodological flaws, the low power and a short follow-up of the surveys, this statement cannot however aspire to a high stability.

Breast Neoplasms↗
PubMed2004

[Identification and management of hereditary predisposition to cancer of the breast and the ovary (update 2004)].

BACKGROUND: Since the last recommendations, up to 2,500 new references had been published on that topic. METHODOLOGY: On the behalf of the health Minister, the Ad Hoc Committee consisted of 13 experts carried out a first version revisited by five additional experts who critically analyzed the first version of the report. MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer deleterious mutation of BRCA12 and BRCA2 than previously thought. The screening of ovarian cancer is still not an attractive option while in contrast MRI may be soon for these young women with dense breast, the recommended option for breast cancer screening. The effectiveness of prophylactic surgeries is now well established. French position is to favor such surgeries with regard to a quality of life in line with the expected benefit, and providing precise and standardized process described in the recommendation. CONCLUSIONS: Due to methodological flaws, the low power and a short follow-up of the surveys, this statement cannot however aspire to a high stability.

Breast Neoplasms↗
PubMed2004

[Identification and management of HNPCC syndrome (hereditary non polyposis colon cancer), hereditary predisposition to colorectal and endometrial adenocarcinomas].

BACKGROUND: The HNPCC syndrome (hereditary non polyposis colon cancer) is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for small intestine, urothelial, ovary, stomach and biliary tract carcinomas. HNPCC syndrome is responsible for 5% of colorectal cancers. Identification and management of this disease are part of a multidisciplinary procedure. METHODS: 12 experts have been mandated by the French Health Ministry to analyze and synthesize their consensus position, and the resulting document has been reviewed by an additional group of 4 independent experts. MAIN RECOMMENDATIONS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a 2-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks, but other organs being at low lifetime risk, no specific surveillance will be proposed.

Adenocarcinoma↗
PubMed2003

Impact of gene patents on the cost-effective delivery of care: the case of BRCA1 genetic testing.

BACKGROUND: In 1994/95, two genes, BRCA1/2, associated with a predisposition to breast or ovarian cancer were identified. Genetic testing of deleterious BRCA1/2 mutations consequently can be proposed to individuals with a family history of breast or ovarian cancer to identify who is at risk. The granting of U.S. patents on BRCA1/2 to a privately owned company has led to the monopoly use of a unique technique (Direct Sequencing of the gene, DS) for BRCA1/2 testing in this country. Alternative strategies using prescreening techniques, however, have been experienced worldwide. METHODS: On the basis of data collected at three laboratories of French public hospitals, we carried out a cost-effectiveness study comparing DS to 19 alternative strategies with the number of deleterious BRCA1 mutations detected as the outcome. RESULTS: Results show that the DS strategy presents the highest average cost per mutation detected (9,882.5 Euro) and that there exist strategies using prescreening techniques that can reach similar effectiveness while reducing total costs. Moreover, other strategies can obtain a four- to sevenfold reduction in the average cost per mutation detected as soon as some rates of false negatives (2% to 13%) are deemed to be acceptable. CONCLUSIONS: Results suggest that gene patents with a very broad scope, covering all potential medical applications, may prevent health care systems from identifying and adopting the most efficient genetic testing strategies due to the monopoly granted for the exploitation of the gene. Policy implications for regulatory authorities, in the current context of the extension of BRCA1/2 patents in other countries, are discussed.

Breast Neoplasms↗
PubMed2002

[Biomedical research and conflicts of interest].

"PLURAL" RESEARCH: Research is no longer an individual activity but is now "plural" and therefore induces conflicts of interests. Using conflicts of interests as an analytical grid, as such, allows to shrug off value judgements. Good and evil are no more at stake and interests enlightened the actions of the various parties. SOME EXAMPLES: The patient versus patients leading to the paradigmatic case of sacrifice. Is it allowed to sacrifice one human being on purpose to increase the benefit of many? Researcher (the agent of science) versus physician (the agent of the patient). Patients versus patients (struggle for funding). Manufacturers versus researchers. The simplifying view of "big investors" versus "immaculate research" is superimposed on the metaphor of Goliath versus David. HYPOTHESIS: Truly the point here argued is that it is not an ethical and individual concern but an organizational issue. The key question is: therefore what kind of rule, what kind of organization should lead to increase efficacy and to reduce tension among the parties involved?

Biomedical Research↗
PubMed2002

[The appropriateness of the indications and diagnostic efficiency of colonoscopy. Results of a survey conducted in all the hospital centers of the Provence-Alpes-Côte d'Azur area].

OBJECTIVE: To evaluate the appropriateness of indications and the diagnostic efficiency of colonoscopy taking into account available guidelines. METHODS: This was a retrospective study conducted by the Union Régionale des Caisses d'Assurance Maladie de Provence-Alpes-Côte d'Azur (URCAM-Paca) aimed at assessing the appropriateness of the indications and diagnostic efficiency of colonoscopy. Anonymous data concerning near totality of the colonoscopies carried out during one week in all the establishments (public and private) of the area, were collected by consulting the medical records. RESULTS: The indications for colonoscopy were first analyzed with regard to the guidelines for good clinical practices (références médicales opposables and consensus conference) according to two scales of reading (literal interpretation and broad interpretation). We noted that the available guidelines do not cover the totality of the colonoscopies performed, that their formulation does not make them all controllable, and that the colonoscopies, which respect them, range from 27.5% (strict reading) to 74.1% (broad reading). When taking into account not only the quality of the preparation, but also the result of the examination after re-classification into benign, pathological or normal examinations, the differences in efficiency appear only when one retains the broad interpretation of the reference guidelines. The efficiency analysis makes it possible to highlight a defect of predictability of the recommendations with regard to the pathologies considered as serious. It also appears that approximately 10% of the colonoscopies are, at the same time, out of the reference and have a normal result, and thus can be considered as absolutely not justified. CONCLUSION: Better compliance of the practitioners to colonoscopy recommendations would initially be generated by improvement in the predictability and the legibility of the current reference guidelines.

Colonoscopy↗
PubMed2002

Gene expression profiles of poor-prognosis primary breast cancer correlate with survival.

The extensive heterogeneity of breast cancer complicates the precise assessment of tumour aggressiveness, making therapeutic decisions difficult and treatments inappropriate in some cases. Consequently, the long-term metastasis-free survival rate of patients receiving adjuvant chemotherapy is only 60%. There is a genuine need to identify parameters that might accurately predict the effectiveness of this treatment for each patient. Using cDNA arrays, we profiled tumour samples from 55 women with poor-prognosis breast cancer treated with adjuvant anthracycline-based chemotherapy. Gene expression monitoring was applied to a set of about 1000 candidate cancer genes. Differences in expression profiles provided molecular evidence of the clinical heterogeneity of disease. First, we confirmed the capacity of a 23-gene predictor set, identified in a previous study, to distinguish between tumours associated with different survival. Second, using a refined gene set derived from the previous one, we distinguished, among the 55 clinically homogeneous tumours, three classes with significantly different clinical outcome: 5-year overall survival and metastasis-free survival rates were respectively 100% and 75% in the first class, 65% and 56% in the second and 40% and 20% in the third. This discrimination resulted from the differential expression of two clusters of genes encoding proteins with diverse functions, including the estrogen receptor (ER). Another finding was the identification of two ER-positive tumour subgroups with different survival. These results indicate that gene expression profiling can predict clinical outcome and lead to a more precise classification of breast tumours. Furthermore, the characterization of discriminator genes might accelerate the development of new specific and alternative therapies, allowing more rationally tailored treatments that are potentially more efficient and less toxic.

Breast Neoplasms↗
PubMed2002

Genome-wide search for loss of heterozygosity in Burkitt lymphoma cell lines.

The molecular biological characteristics of Burkitt lymphoma (BL), in addition to the presence of the Epstein-Barr virus (EBV) in some forms, relies on well-characterized alterations, such as MYC translocations and TP53 inactivations. To ascertain the number and location of other genome alterations, we used 191 polymorphic markers in a genome-wide search for loss of heterozygosity (LOH) in 31 Burkitt lymphoma cell lines and their normal counterparts. We were able to distinguish two types of altered allelic patterns: a bona fide LOH profile, indicative of deletion (LOH), and a profile indicative of increased dosage (ID). The former type was most frequent at chromosome arm 17p, most likely indicating TP53 gene inactivation. Increased dosage at 1q was found almost exclusively in non-EBV cell lines (P < 0.00004) and correlated well with karyotypic abnormalities affecting region 1q21-25. Our results suggest that a gene important for BL pathogenesis is located in region 1q21-25 and that the activation of this gene mimics the effects of EBV.

Adolescent↗
PubMed2002

Distinct and complementary information provided by use of tissue and DNA microarrays in the study of breast tumor markers.

Emerging high-throughput screening technologies are rapidly providing opportunities to identify new diagnostic and prognostic markers and new therapeutic targets in human cancer. Currently, cDNA arrays allow the quantitative measurement of thousands of mRNA expression levels simultaneously. Validation of this tool in hospital settings can be done on large series of archival paraffin-embedded tumor samples using the new technique of tissue microarray. On a series of 55 clinically and pathologically homogeneous breast tumors, we compared for 15 molecules with a proven or suspected role in breast cancer, the mRNA expression levels measured by cDNA array analysis with protein expression levels obtained using tumor tissue microarrays. The validity of cDNA array and tissue microarray data were first verified by comparison with quantitative reverse transcriptase-polymerase chain reaction measurements and immunohistochemistry on full tissue sections, respectively. We found a good correlation between cDNA and tissue array analyses in one-third of the 15 molecules, and no correlation in the remaining two-thirds. Furthermore, protein but not RNA levels may have prognostic value; this was the case for MUC1 protein, which was studied further using a tissue microarray containing approximately 600 tumor samples. For THBS1 the opposite was observed because only RNA levels had prognostic value. Thus, differences extended to clinical prognostic information obtained by the two methods underlining their complementarity and the need for a global molecular analysis of tumors at both the RNA and protein levels.

Base Sequence↗
PubMed2002

Effects of genetic consultation on perception of a family risk of breast/ovarian cancer and determinants of inaccurate perception after the consultation.

The aim of this study was to assess the effects of cancer genetic consultations on women's perception of their family risk of breast/ovarian cancer, and to determine which factors were associated with an inaccurate perception after the consultation. A multicenter prospective survey was carried out on women (n = 397) attending cancer genetic clinics in France for the first time, in which the perceived family risk was measured both before and after the consultation, using self-administered questionnaires. The effects of the consultation on risk perception were significant among low (P <.001) and moderate risk women (P <.05). However, after the consultation, 76.3% of the "low"-risk women did not perceive their family as "low"-risk families, and 21.9% of the moderate-risk women were still definitely sure there was a genetic risk running in their family. The consultation did not affect the family risk perception of the high risk women (n = 171): the risk was thought to be very high both before (87.7%) and after (89.5%) the consultation (NS); however 10.5% of this group still perceived their family as being unlikely to be at risk after the consultation. In the low- and moderate-risk groups after multivariate adjustment, the inaccurate perceptions varied, depending on the clinics and on the psychosocial context of the consultation: they increased when the consultee was personally affected by cancer, and decreased when the consultee had a health occupation. Cancer genetic consultations had only marginal effects on the perception of family risk on the whole, although they were significant in the case of low- and moderate-risk women. The question arises as to whether a more comprehensive approach should be implemented and how to go about providing efficient cancer risk information in the context of health care systems.

Adult↗
PubMed2002

Testing for BRCA1 mutations: a cost-effectiveness analysis.

Breast carcinoma is the most common type of cancer affecting women in the Western world. The hereditary forms, which amount from 5 to 10% of all the cases of breast cancer, mainly involve BRCA1 or BRCA2 mutations. Due to the diagnostic strategy used by the patent owner, Direct DNA sequencing (DS) may become the only BRCA1/2 test procedure available, although there exist several alternative strategies. A cost-effectiveness study was carried out using BRCA1 testing as a model. The main techniques available for performing mutation searches were assessed: DS, denaturing high performance liquid chromatography (DHPLC), single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), heteroduplex analysis (HA), fluorescent assisted mismatch analysis (FAMA) and the protein truncation test (PTT). Twenty strategies involving the use of one or more techniques were then devised for performing the complete genetic analysis. DS was adopted as the 'gold standard' for effectiveness. All the strategies except for DS involved a two-step procedure. The first step consisted of pre-screening the 22 coding exons of BRCA1. The second step consisted of performing DS only on the variations detected in the coding sequence. The cost of the strategies tested, including a pre-screening stage, turned out to be 30 to 90% lower than that of DS, whatever annual use was made of the equipment. The most cost-effective strategy, ie, that corresponding to the lowest cost per mutation detected, was found to be a combination between PTT on exon 11 (60% of the coding sequence) and HA on the remaining 21 exons (PTT(11)+ HA(21)). However, since a high false negative rate is associated with this strategy, at least four other strategies are worth mentioning: PTT(11)+ DHPLC(21), DHPLC alone, FAMA(11)+ DHPLC(21) and FAMA alone. Our results on genetic testing for breast cancer show that DS is not the most cost-effective method available. The monopolist approach of the firm which owns the patents on the BRCA1/2 genes, may, therefore limit the use of the most cost-effective strategies.

Cost-Benefit Analysis↗