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F Eisinger

Publications and source records attributed to F Eisinger.

At least 73 records · Page 4Linked to original sources
PubMed1997

Loss of heterozygosity in human breast carcinomas in the ataxia telangiectasia, Cowden disease and BRCA1 gene regions.

To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with particular emphasis on specific regions. No site of consistent LOH was identified on chromosome 10. Five regions of LOH were contained within bands q22-24 of chromosome 11 for which nearly 50% of the tumors had LOH at at least one marker. This region is thus a major site of deletion in breast cancer and several tumor suppressor genes seem to be involved. One of them may be the ataxia telangiectasia (ATM) gene which is located in one of the affected regions. Five regions of LOH, one of which is within the BRCA1 gene area, were recognized along chromosome 17. LOH at three of these regions were found in highly proliferative tumors. When combined with a previous study of chromosome 13 with emphasis on BRCA2 and Rb1 genes, this work allowed to distinguish a total of 12 regions of LOH, variably affected in breast tumors and correlated with prognostic parameters.

Alleles↗
PubMed1996

Truncation at conserved terminal regions of BRCA1 protein is associated with highly proliferating hereditary breast cancers.

The existence of two subgroups of BRCA1-associated breast cancer (BC) families has been recently posited: the first with highly proliferating tumors, and the second composed of cases with a low proliferation rate. Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the site of the germ line mutation in the BRCA1 gene. We analyzed the distribution of the mitotic index, a histoprognostic grade component shown to segregate in families, matching for germ line mutation location in a series of 28 breast cancers from 20 kindreds. We observed a prevalence of highly proliferating tumors when the mutation occurs in the two terminal conserved domains of the BRCA1 protein, ie., in the amino and carboxyl termini (P = 0.0024). Our data provide evidence for a genotype-phenotype correlation and along with their strong conservation during evolution argue for the importance of these two regions in the control of mammary cell growth.

Alleles↗
PubMed1996

Germ line mutation at BRCA1 affects the histoprognostic grade in hereditary breast cancer.

Histoprognostic grade is a determinant parameter to select the initial therapeutic strategy in breast cancer. Our aim was to analyze the grade repartition in BRCA1-associated breast cancer (BC) and to explore the possible connections between grade and the BRCA1 gene function. We first compared 27 BRCA1-associated BCs from 14 families with 4,461 cases from an administrative district registry and 242 cases from a hospital-based registry, matching for grade and constitutive elements, and then considered their repartition in families. We observed a prevalence of grade 3 (P < 0.0001) in BRCA1-associated BC. This was attributed mainly to nuclear polymorphism (P < 0.0001), mitotic activity (P < 0.0001), and tubular differentiation (P = 0.0004), implying that BRCA1-associated BCs are highly proliferating tumors. Moreover, it is suggested that grade segregates as a genetic trait within families (P = 0.0015), and this was attributed to the mitotic index segregation only (P = 0.0005). Therefore grade, through its components, could be interpreted as the morphological translation of the BRCA1 germ line mutation. Thus, a genotype-phenotype correlation may exist between the type of mutation and the aggressiveness of the disease. These findings are bound to have an important impact in the care management of hereditary breast cancer at the individual and at the familial level and in the comprehensive approach of breast cancer development.

Adult↗
PubMed1996

Cancer genetics clinics: target population and consultees' expectations.

The aim of this study was to determine in healthy consultees attending cancer genetics clinics their risk status, their pathways leading to the clinics, their expectations and perception of cancer risk. In 1994, the consultees at six French centres completed a questionnaire before their first oncogenetic consultation. The oncogeneticists subsequently filled in a standardised form giving their risk assessment. Among the 206 healthy consultees, 91.3% were women, 92.2% had at least one cancer-affected first-degree relative and 73% had a "cancer family risk" as assessed by the oncogeneticist. Sixty-nine per cent of the consultees were referred to the clinics by a physician, 10.4% by their family and 18.8% on their own initiative: 83.5% of the sample perceived their family risk of cancer as being high and this belief was confirmed in 74.3% of the cases studied by the oncogeneticist. The families of self-referred consultees were less often at risk than those of consultees referred by a physician or by their family (P = 0.012). The majority (78%) expected to be informed about cancer prevention and screening, and this expectation depended on the consultee's level of education (P = 0.001). This study shows that medical pathways are more effective than the media as a means of reaching the members of the general population who are genuinely at risk, and shows that fuller information about prevention needs to be provided at cancer genetic consultations.

Adult↗
PubMed1996

Attitudes towards cancer predictive testing and transmission of information to the family.

Before the organisation of breast cancer predictive testing in France, consultands' attitudes towards this kind of testing and towards passing on information about the family cancer risk to their relatives were investigated. This survey was carried out from January 1994 to January 1995 at six specialised cancer genetic clinics located in different parts of France Female consultands who were first degree relatives of cancer patients and who had at least one case of breast cancer in their family, affecting either themselves or a first degree relative or both, participated in this study. Among the 248 eligible consultands attending the clinics during the study period, 84.3% answered a post-consultation questionnaire. Among the 209 respondents, 40.7% (n = 85) were cancer patients and 59.3% (n = 124) were healthy consultands. A high consensus in favour of genetic testing was noted, since 87.7% of the sample stated that they would ask for breast cancer gene testing if this test became available. The underlying assumption of 96.6% of the women was that their health surveillance would be improved after a positive test. A high awareness of the anxiety that would be generated in a family after a positive result was observed and found to be associated (p < 0.05) with the anxiety and depressive profiles of the patients. Half of the healthy respondents said they would not change their attitude towards screening if the results of predictive testing turned out to be negative. Only 13.7% of the 161 patients who stated that the oncogeneticists asked them to contact their relatives firmly refused to do so, mainly because of difficult family relationships.

Adult↗
PubMed1996

[Attitudes towards screening and prevention of breast and ovarian cancers with hereditary predisposition. Survey by female gynecologists in the north of France].

Search for mutations of BRCA1 in women at hereditary risk for cancer is now possible. We asked the female gynaecologists of our county (north of France) their opinion about the search of a mutation of BRCA1 if they had a familial risk of breast cancer. Our aim was to obtain the opinion of informed women about their willingness to do the test for themselves and about the consequences they should accept. One hundred and eighty-three women received a questionnaire by post. The response rate was 56.3%. Twenty-four percent of the responders had a first degree relative with breast cancer. Most of the responders (87.4%; IC 95%: 81-93.8) would ask for the search of a mutation of BRCA1. The percentage of women who would accept the test is smaller for the women who have a first degree relative with breast cancer (72.0% vs 92.3%; P = 0.02). The reasons given to do the test were a better screening or prevention (69.7%) and the knowledge of a personal risk (49.4%). For breast cancer, 93.2% (95% CI: 88.4-98) would accept a screening protocol, 30.1% (CI: 21.3-38.9) would accept a prophylactic bilateral mastectomy. For ovarian cancer, 93.2% (CI: 88.4-98) would accept the screening, 52.4% (CI: 42.8-62) would accept a prophylactic ovariectomy. In conclusion, most of the informed women would ask for the test and the surgical options for reducing the risk of cancer are not absolutely rejected. Of course, only future studies will state precisely the choice of truly implicated women.

Adult↗
PubMed1996

[Screening practices and familial antecedents of colorectal cancer. Survey with a voluntary population].

OBJECTIVES: To analyze the association between colorectal cancer positive family history and screening practices. METHODS: The study concerned 6733 individuals attending a center for periodic health examination. RESULTS: Five hundred fifty four patients (8.2%) declared a positive family history of colorectal cancer; 269 (4%) were first degree relatives of the affected member and among them, 73 (1.1%) have pointed out the occurrence of at least one cancer case below age 50. Out of 554 subjects with a family history (regardless the degree of kinship), 132 (23.8%) have had an endoscopic examination versus 8.9% of subjects without positive family history. The rate of endoscopy increased with the number of cases in a family (P < 0.0001). CONCLUSION: Family members undertake more endoscopic examinations when a family history of colorectal is reported. A correlation with the number of affected relatives has been found.

Adult↗
PubMed1995

Loss of heterozygosity and linkage analysis in breast carcinoma: indication for a putative third susceptibility gene on the short arm of chromosome 8.

We have analysed losses of heterozygosity (LOH) at eight markers from the p12-p22 region of human chromosome 8 in a panel of 113 breast tumors. LOH were detected in almost half of the tumors. The most frequently deleted region included microsatellite (CA)n repeats markers D8S258, D8S133 and D8S259, located at 8p12-p22, while markers NEFL and LPL appeared less frequently altered. In parallel, linkage analysis was performed using the same informative markers, to test for the involvement of chromosome 8p loci in familial breast cancer. Positive cumulative multipoint lod score of 2.51 at theta = 0.0 was obtained with markers NEFL and D8S259. These results suggest that region 8p12-p22 carries at least one tumor suppressor gene involved in sporadic and perhaps also in familial breast cancer.

Breast Neoplasms↗
PubMed1995

[Prevention and chemoprevention in cancerology. A quantitative analysis of medical literature].

Prevention is seen as a major concept of medical literature even distorted by two prisms: search through key-words and an unique referring: The Medline data bank. This topic is as important as "cancer": found in more than 8% of all the articles of this data base. Nine years have been studied (1985-1993) and the mean rise for the appearance of the word "prevention" is +25% a year. The topic "chemoprevention" is quantitatively unimportant: in 1993 0.07% of the whole corpus mentioned it, and as few as 0.8% of the prevention-related articles, however this topic has demonstrated a dramatic rise: a mean of +150% a year through the nine years studied (and +250% between 1992 and 1993). This topic of "chemoprevention" appears specially in connection with cancerology which seems to be a preferential field for this approach: more than 80% of the articles selected by "chemoprevention" refers also to "cancer". Finally, in the restrictive frame of "the upstream treatment", search on "hope" topic evokes a shift from early diagnosis to prevention.

Abstracting and Indexing↗
PubMed1995

[Medical chemoprevention of cancers. From the point of view of social sciences].

The orientation of the medical activity toward preventive strategies knows currently an important development. This movement shows various logic, which are: on one hand a rational step, a strategic choice in favour of prevention, and on the other hand a choice by elimination, when the other forms of intervention establish insufficient efficiency. Prevention had to follow the path of validity to acquire pertinence. The gold-standard is randomised blinded trials and it is this kind of procedure that has been proposed in the BCPT (Breast cancer prevention trial). By comparison with a classic therapeutic trial the main differences of prevention trial lay in: criteria of inclusion, analyses of impact larger than the simple efficiency (quality of life), on the focus on the risk (especially genetic) and the legal context. One of the main points is the question of risks induced by an intervention on healthy persons. In this context, even the passage of an uncertainty to a "certainty" concerning induced risks can not always suffice to close the controversy. Physicians cannot in this case, refer to norms and to models since this type of intervention is new.

Antineoplastic Agents↗
PubMed1995

[Methodology and legitimacy of French clinical trials in primary chemoprevention of cancers. The point of view of the National Federation of French cancer centers].

In connection with the breast cancer prevention trial (BCPT) controversy, the "Fédération nationale des centres de lutte contre le cancer" (FNCLCC) decided to clarify, with the help of various discipline experts, its position on chemoprevention trials. If in terms of inclusion, two approaches can be opposed: high relative risk versus high attributable risk, these trials share in common a considerable importance of the informed consent according to potentially prosecution. A particular attention should be given to the unambiguous definition of end-points and indicators, and to monitoring of the side effects (medical or not). Non medical actors would have to play significant interventions in the schedule, the follow-up and the evaluation of such protocols. Methodological difficulties have been pointed, for example: recruitment, observance, drop out and confounding factors. French specificity has to be taking into account for the choice of pathologies, kind of interventions and global evaluation non limited to the sole dimension of the medical efficiency.

Antineoplastic Agents↗