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D Stoppa-Lyonnet

Publications and source records attributed to D Stoppa-Lyonnet.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Inserm ad hoc committee: Recommendations for the management of women with a genetic risk for developing cancer of the breast and/or the ovary].

BACKGROUND: Almost 10% of breast and ovarian cancer are inherited, and the majority are linked to BRCA1 and BRCA2 germline mutations. Despite the uncertainty, consensus guidelines were defined to assist practitioners', and patients' decisions about the health care decisions to be made. METHODOLOGY: The ad hoc committee consisted of 14 experts designated by the French National Institute for Health and Medical Research. They all attended eleven workshops at which a systematic analytical review of more than 3,500 articles was carried out. Five additional experts critically analyzed the first version of the report. PROCESS: Two thresholds were defined on a probability scale giving the risk of developing breast or ovarian cancer, to serve as a means of deciding as whether an intervention is worthwhile. The first threshold is that above which an intervention can be envisaged or recommended; the second is that under which an intervention can be ruled out; between the two, the decision has to be made on a each by case basis. SCREENING AND PREVENTIVE STRATEGIES ANALYZED: About breast cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning and chemoprevention); 3) screening (breast self-examination, clinician breast examination, tumor markers, imaging); 4) prophylactic mastectomy. About ovarian cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and tumor markers); 3) prophylactic oophorectomy. MAIN CONCLUSIONS: With each strategy the following points were dealt with: the information to be delivered to the consult and, the procedure and the indications. The committee's opinion about BRCA mutation screening is that population-based or even large scale implementation are not justified. The committee feels that specific management is indispensable and advocates the use of defined and evaluated procedures, and involvement in clinical trials.

Age Factors↗
PubMed1999

[INSERM-FNCLCC collective expertise. Recommendations for medical management of women with genetic risk of developing breast and/or ovarian cancer].

BACKGROUND: Almost 10% of breast and ovarian cancer are inherited, and the majority are linked to BRCA1 and BRCA2 germline mutations. Despite the uncertainty in the management of women gene carriers, consensus guidelines were defined to assist practitioners', and patients' decisions about the health care decisions to be made. METHODOLOGY: The Ad Hoc Committee consisted of 14 experts designated by the French National Institute for Health and Medical Research. They all attended eleven workshops at which a systematic analytical review of more than 3500 articles was carried out. Five additional experts critically analysed the first version of the report. CRITERIA AND DECISION PROCESS: Two thresholds were defined on a probability scale giving the risk of developing breast or ovarian cancer, to serve as a means of deciding as whether an intervention is worthwhile. The first threshold is that above which an intervention can be envisaged or recommended; the second is that under which an intervention can be ruled out; between the two, the decision has to be made on a each by case basis. STRATEGIES ANALYZED: About breast cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning and chemoprevention); 3) screening (breast self-examination, clinician breast examination, tumor markers, imaging); 4) prophylactic mastectomy. About ovarian cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and tumor markers); 3) prophylactic oophorectomy. MAIN CONCLUSIONS: With each strategy the following points were dealt with; the information to be delivered to the Consultant, the procedure and the indications. In addition, the Committee's opinion about BRCA1 and BRCA2 mutation screening is that population-based or even large scale implementation are not justified. Although no scientific evidence is available, the Committee feels that specific management is indispensable and advocates the use of defined and evaluated procedures, and involvement in clinical trials.

BRCA1 Protein↗
PubMed1998

Marker segregation information in breast/ovarian cancer genetic counseling: is it still useful? Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer.

The use of mutation screening of BRCA1 and BRCA2 genes as a genetic test is still to a certain extent limited and the oncogeneticist may want to use complementary approaches to identify at-risk individuals. In a series of 23 families with at least three breast or ovarian cancer cases, screened for mutations at BRCA1 and BRCA2 and typed for markers at both loci, we investigated the usefulness of marker segregation information at two levels: 1) to what extent can the indirect approach identify the mutation carrier status of screened cases and their first-degree relatives, and 2) in what way does it help to identify the gene implicated in a family in which neither BRCA1 nor BRCA2 mutation has been detected? Using the indirect approach, the carrier status of the screened case could be determined with quasi certainty in three families and with a high probability in eight families. This status could be inferred in unaffected first-degree relatives as almost certain in one family and as highly probable in six families. Fourteen mutations were found concurrently in our series. Among the nine mutation-negative families, we were able to conclude that a BRCA1 mutation most probably segregated in one and that a mutation other than BRCA1 and BRCA2 was probably involved in two families. Our results show that, in small families, little help is to be expected from linkage data and mutation screening is the only way of identifying the origin of a genetic predisposition in a family. Marker segregation information may be useful in some large breast/ovarian cancer families in which no BRCA1 or BRCA2 mutation has been detected.

BRCA1 Protein↗
PubMed1998

Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations.

BACKGROUND: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. METHODS: Specimens of tumor tissue (5-microm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. RESULTS: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. CONCLUSIONS: Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.

Adult↗
PubMed1998

Inactivation of the ATM gene in T-cell prolymphocytic leukemias.

T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature leukemia that occurs both in adults as a sporadic disease and in younger patients suffering an hereditary condition, ataxia telangiectasia (AT). The ATM gene, located in the 11q22-23 chromosomal region, is consistently mutated in AT patients. The strong predisposition of AT patients to develop T-PLL and the high frequency of T-cell leukemias/lymphomas observed in atm-deficient mice, together with the known functions of the ATM protein, led us to evaluate the ATM gene as a potential tumor suppressor gene involved in T-PLL. Paired leukemic and nonleukemic cells were obtained from a series of 15 patients suffering sporadic T-PLLs, allowing loss of heterozygosity (LOH) analysis. LOH of the 11q22-23 region was detected in 10 of these 15 cases (67%). The minimal deleted region was defined as an approximately 2.5 Mb interval that contained the ATM gene. No ATM rearrangement or biallelic deletion was detected by Southern blotting in the T-PLL series. However, in five T-PLLs with LOH of the 11q22-23 region, Western blot analysis showed either undetectable (3 cases) or decreased levels (1 case) of ATM protein, whereas ATM was present at high levels in cases without LOH. The protein truncation test (PTT) was then used to search for mutations in the ATM gene. Four mutations (1 nonsense, 2 aberrant splicings, and 1 missense) were detected in patients with LOH and none in patients without LOH of the region. The acquired character of these ATM mutations was demonstrated in three patients. Altogether, allelic ATM inactivations by large deletions or mutations were found in approximately two thirds of T-PLL. ATM is thus a tumor suppressor gene whose inactivation is a key event in the development of T-cell prolymphocytic leukemias.

Adult↗
PubMed1998

Mutations at BRCA1: the medullary breast carcinoma revisited.

BRCA1-associated breast cancers (BRCA1-BCs) frequently harbor a high histoprognostic grade, p53 alterations, and estrogen receptor negativity. Although these parameters predict a poor outlook, the overall survival in BRCA1-BCs is equivalent to or even better than that in sporadic cases. These features are reminiscent of what is observed for breast carcinoma of the medullary type, a high-grade tumor with a particular favorable course. To explore a possible relationship between this phenotype and BRCA1 mutations, we first compared 32 BRCA1-BCs and 200 consecutive cases of breast cancer without familial history for the prevalence of typical medullary breast carcinoma (TMC) using the criteria given by Ridolfi et al. [R. Ridolfi et al, Cancer (Phila.), 40: 1365-1385, 1977]. Second, we searched for BRCA1 mutations in a set of 18 cases of TMC, using denaturing gradient gel electrophoresis and Cleavase fragment length polymorphism scanning. Six of 32 (19%) BRCA1-BCs were of the TMC type, compared to 0 of 200 controls (P < 0.0001). Among the 18 TMCs, 2 BRCA1 nonsense mutations were found. This corresponds to almost 7 times the contribution of BRCA1 mutations in the general population. Two additional missense mutations were identified. Together, these results suggest that, although TMC and BRCA1-BCs are not strictly coincidental, an important connection between the two populations does exist.

BRCA1 Protein↗
PubMed1998

Recommendations for medical management of hereditary breast and ovarian cancer: the French National Ad Hoc Committee.

BACKGROUND AND PURPOSE: Almost 10% of breast and ovarian cancers are familial, and the majority are linked to BRCA1 and BRCA2 germline mutations. Despite uncertainty about the management of female gene carriers, consensus guidelines have been established to assist practitioners and consultees in making health care decisions. METHODOLOGY: The Ad Hoc Committee was composed of 14 experts appointed by the French National Institute for Health and Medical Research, all of whom attended eleven workshops at which more than 3500 articles were systematically analyzed. Five additional experts critically analysed the first version of the report. CRITERIA AND DECISION PROCESS: On a probability scale of the risk of developing breast or ovarian cancers, two thresholds were defined for use in determining whether an intervention would be worthwhile. The first is the threshold above which an intervention can be envisaged or recommended, and the second is the one below which an intervention can be ruled out; between the two, the decision has to be made on a case-by-case basis. SCREENING AND PREVENTIVE STRATEGIES ANALYZED: With respect to breast cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning and chemoprevention); 3) screening (breast self-examination, clinician breast examination, tumor markers, imaging); 4) prophylactic mastectomy. With respect to ovarian cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and tumor markers); 3) prophylactic oophorectomy. MAIN CONCLUSIONS: For each strategy the following points were addressed: the information to be given to the consultee, the procedure and the indications. In addition, the committee's opinion about BRCA1 and BRCA2 mutation screening is that population-based, or even large-scale, implementation are not justified. Although no scientific evidence is available, the committee feels that specific management is indispensable and advocates the use of defined and evaluated procedures, and participation in clinical trials.

Breast Neoplasms↗
PubMed1998

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study.

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P<.001), although only 8% of the variance in age at diagnosis could be explained by the specific mutation, and there was no evidence of family-specific effects. When the age at diagnosis of the breast cancer cases was examined by OCCR, cases associated with mutations in the OCCR had a significantly older mean age at diagnosis than was seen in those outside this region (48 years vs. 42 years; P=.0005).

Adult↗
PubMed1998

Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group.

Germline mutations in the p16 and CDK4 genes have been reported in a subset of melanoma pedigrees, but their prevalence is not well known. We searched for such germline mutations in 48 French melanoma-prone families selected according to two major criteria: families with at least three affected members (n = 20) or families with two affected members, one of them affected before the age of 50 (n = 28), and one additional minor criterion. Sixteen different p16 germline mutations were found in 21 families, while one germline mutation, Arg24His, was detected in the CDK4 gene. The frequency of p16 gene mutation in our sample (44%) is among the highest rates yet reported and the CDK4 mutation is the second mutation detected in this gene worldwide. In summary, our results show frequent involvement of the p16 gene in familial melanoma and confirm the role of the CDK4 gene as a melanoma-predisposing gene.

Adult↗
PubMed1998

[INSERM-FNCLCC collective expert's report. Recommendations for management of women having a genetic risk of developing breast and/or ovarian cancer. National Federation of Centers of the Fight Against Cancer].

BACKGROUND: Almost 10% of breast and ovarian cancer are inherited, and the majority are linked to BRCA1 and BRCA2 germline mutations. Despite the uncertainty, consensus guidelines were defined to assist practitioners', and patients' decisions about the health care decisions to be made. METHODOLOGY: The Ad Hoc Committee consisted of 14 experts designated by the French National Institute for Health and Medical Research. They all attended eleven workshops at which a systematic analytical review of more than 3500 articles was carried out. Five additional experts critically analyzed the first version of the report. PROCESS: Two thresholds were defined on a probability scale giving the risk of developing breast or ovarian cancer, to serve as a means of deciding as whether an intervention is worthwhile. The first threshold is that above which an intervention can be envisaged or recommended; the second is that under which an intervention can be ruled out; between the two, the decision has to be made on a each by case basis. SCREENING AND PREVENTIVE STRATEGIES ANALYZED: About breast cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning and chemoprevention); 3) screening (breast self-examination, clinician breast examination, tumor markers, imaging); 4) prophylactic mastectomy. About ovarian cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and tumor markers); 3) prophylactic oophorectomy. MAIN CONCLUSIONS: With each strategy the following points were dealt with: the information to be delivered to the consultant, the procedure and the indications. The Committee's opinion about BRCA mutation screening is that population-based or even large scale implementation are not justified. The Committee feels that specific management is indispensable and advocates the use of defined and evaluated procedures, and involvement in clinical trials.

Anticarcinogenic Agents↗
PubMed1998

[Psychosocial impact of the first oncogenetic consultation in a familial context of cancers of the breast and the ovary].

The purpose of the oncogenetic consultation, is to respond to persons who wonder about their risk of developing a tumour and wish to learn about ways of prevention and detection. The object of this investigation is (1) to study the impact of a first consultation in genetics on the quality of life and the psychology of women with a family history of cancer, and women with or without family antecedents but who suffered themselves from breast cancer at an early age (< or = 35 years); (2) to evaluate their risk perception and their comprehension of the information after the consultation. The study was performed on 200 women attending a first consultation at Institut Curie. Fifty-nine of them had no cancer. Among the 141 consultants with cancer, 54 had developed breast cancer at an early age (< or = 35 years). Their quality of life, their psychological state and their knowledge of the risk of breast tumour were evaluated before consulting and 6-8 months afterwards. Before consulting, their quality of life was altered in some (non-relational) fields but their psychic condition was relatively maintained. Six-nine months after consulting, their quality of life had not deteriorated, but tests results on their psychological state were not as good. The initial psychic condition, itself related to the medical status of the consulting women, was the most significant predictor of their quality of life a few months after their first genetics consultation. After consulting, the women expressed satisfaction with the information delivered by the genetician and their appreciation of tumour risks was improved.

Adult↗
PubMed1997

[Genetic predispositions to breast cancer].

NEW DATA: Genetic epidemiology and position cloning techniques have made it possible to estimate the risk women with a family history of breast cancer have of developing a breast tumor. THREE PREDISPOSITION GENES: Three BReast CAncer genes (BRCA1, BRCA2 and BRCA3) have been localized on chromosomes 17 13 and 8. It is highly likely that other genes also have an influence. GENETIC TESTING: When an altered BRCA1 or BRCA2 gene is identified in a family, a gene test can be proposed to recognize predisposition in relatives. A negative test means the subject is not predisposed to breast cancer and that transmission to offspring is not possible. Inversely, the risk of breast cancer is high if the mutation is detected, raising the difficult problem of counselling, particularly in young subjects. PROBLEMS RELATED TO SCREENING TESTS: Screening tests can only be undertaken if the "candidate" is aware of the consequences of the screening results and has had enough time to make a fully informed decision. Confidentiality must be particularly strict, particularly in the field of employment and insurance.

Breast Neoplasms↗