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J Jacquemier

Publications and source records attributed to J Jacquemier.

At least 55 records · Page 3Linked to original sources
PubMed1999

Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes.

Deletions and amplifications are frequent alterations of the short arm of chromosome 8 associated with various types of cancers, including breast cancers. This indicates the likely presence of tumor suppressor genes and oncogenes. In the present study, we have used the expressed sequence tag (EST) map of 8p11-21 to assemble a set of available cDNAs representing genes from this region. DNA arrays were prepared for expression analysis and search for genes potentially involved in breast cancer. Underexpresion in tumoral breast cells (versus normal breast) was observed for 15 transcripts. Among these, the Frizzled-related gene FRP1/FRZB, was turned off in 78% of breast carcinomas, suggesting that the lack of its product may be associated with malignant transformation. Overexpression in tumoral breast cells was observed for 13 genes. The FGFR1 gene, that encodes a tyrosine kinase receptor for members of the fibroblast growth factor family, was identified as a good candidate for one amplification unit. Taken together, our results demonstrate that such a strategy can rapidly identify genes with an altered pattern of expression and provide candidate genes for malignancies.

Breast Neoplasms↗
PubMed1999

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.

A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.

Breast Diseases↗
PubMed1999

Association of angiogenesis and poor prognosis in node-positive patients receiving anthracycline-based adjuvant chemotherapy.

UNLABELLED: Tumoral angiogenesis has been described as associated with poor prognosis in breast cancer, particularly for node negative breast cancer. The purpose of this study was to evaluate the influence of angiogenesis in node-positive breast cancer and particularly its potential impact on adjuvant chemotherapy. PATIENTS AND METHODS: One hundred and thirty-five node-positive breast cancer patients who received anthracycline or derivative based adjuvant chemotherapy were selected from the data base of the Institut Paoli Calmettes. Angiogenesis was evaluated using CD31 antibody. Other prognosis variables studied were: hormonal status, tumor size, hormonal receptors, Elston and Ellis grade, and number of involved lymph nodes. RESULTS: In multivariate analysis, a high level of angiogenesis was independently associated with a diminution of survival (p = 0.007), and of metastasis-free survival (p = 0.003). Other variables associated with poor survival were progesterone receptor status (p = 0.003) and Elston's grade (p = 0.003), and with metastasis-free survival, progesterone receptor status (p = 0.018). CONCLUSION: Tumoral angiogenesis appears to be an independent prognostic factor for node-positive breast cancer, when treated with adjuvant chemotherapy. Adjuvant strategies for patients with a high level of angiogenesis should be discussed.

Adult↗
PubMed1999

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial).

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26-56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m(-2) - doxorubicin (D) 75 mg m(-2) cycle 1, C: 3 g m(-2) - D: 75 mg m(-2) cycle 2, C: 3 g m(-2) - D: 75 mg m(-2) - 5 FU 2500 mg m(-2) cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4-1.04) and 0.96 (range 0.25-1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% +/- 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3-9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% +/- 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome.

Adenocarcinoma↗
PubMed1999

Hormone replacement therapy and screening mammography: analysis of the results in the Bouches du Rhône programme.

OBJECTIVE: To evaluate the effectiveness of a mass screening programme for breast cancer in a French population where hormone replacement therapy (HRT) is common and where mammography is prescribed outside the programme for asymptomatic women. METHODS: From 1993 to 1996 inclusive, 41,062 women underwent a first test and 48,275 a second or third test in the Bouches du Rhône programme. Their HRT status was ascertained at the time of the test. False positive and false negative tests were identified at one year follow up. The incidence of interval cancers was estimated up to three years after the screening test. RESULTS: The odds of being detected at screening rather than as an interval cancer within one year of the test was five times greater among non-users of HRT than among users (odds ratio (OR) 5.14 (confidence interval 2.5 to 11.8)). This high reduction in sensitivity among users (71% v 92%) was associated with a very small reduction in specificity at the incident screen only. The incidence of interval cancers among HRT users was 3.5 times that of non-users within the first year after the test and 1.7 times during the following two years. CONCLUSIONS: When the early results of a programme have been used to measure its effectiveness they should be reassessed in populations where HRT is in widespread use. As interval cancers had better prognostic factors in HRT users than in non-users, the efficacy of a screening programme in such populations should be the subject of further studies.

Aged↗
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

Local and distant recurrence after conservative management of "very low-risk" breast cancer are dependent events: a 10-year follow-up.

PURPOSE: To determine the risk factors associated with recurrence after breast-conserving treatments, and the relationship between occurrence of a local recurrence and subsequent distant metastases. METHODS AND MATERIALS: Among the 3697 patients with primary breast cancer treated at Institut Paoli-Calmettes Cancer Center, Marseille, between 1980 and 1995, we retrospectively analyzed 756 patients who had been treated with conservative surgery with uninvolved margins of excision, were node-negative, and had received uniform radiotherapy and no chemotherapy. One third of the patients received hormonal therapy via tamoxifen or surgical castration. The endpoints considered were local failures and distant metastases. All tumors were reviewed by our pathologists. The median follow-up for the 700 survivors was 62 months. RESULTS: In the multivariate analysis, histological multifocality (p = 0.0076), peritumoral vessel invasion (p = 0.0215), and young age (p = 0.0245) were associated with an increased risk of local recurrences, whereas tumor size (p = 0.0013), young age (p = 0.003), and histological multifocality (p = 0.0414) were associated with an increased risk of distant metastases. Local recurrences and distant metastases had similar yearly-event probabilities. Median time to distant metastases was shorter after a local recurrence. Early timing of local recurrences did not mark a higher risk of distant metastases. Hazard of relapsing from distant metastases was 4.4 times higher after a local recurrence. CONCLUSION: our results support the hypothesis that, in this subset of patients, local recurrences favor further dissemination of cancer cells. We are unable to clearly identify a group who would benefit from more aggressive local therapy.

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

FGF7 protein expression in human breast carcinomas.

FGFs, especially FGF7, are thought to play an important role in the stroma-epithelium interactions that take place in several tissues, including the prostate and mammary glands. Using an immunohistochemistry approach, FGF7 protein expression was measured in a series of 80 human breast carcinomas. FGF7 was found to be expressed in two-thirds of cases studied, either in the stroma or in the tumour cells. Although it did not reach significance level, a tendency was noted for FGF7 expression to be associated with the most differentiated and least aggressive tumours.

Antibodies, Monoclonal↗
PubMed1998

High-dose chemotherapy and haematopoietic stem cell transplantation for inflammatory breast cancer: pathologic response and outcome.

Inflammatory breast cancer still has a poor prognosis despite improvements related to the introduction of neoadjuvant chemotherapy. The purpose of this study was to evaluate pathologic response rate and outcome of patients receiving high-dose chemotherapy with haematopoietic stem cell support for IBC. Seventeen consecutive patients with IBC received an association of mitoxantrone (36 mg/m2), cyclophosphamide (120 mg/kg), melphalan (140 mg/m2), with stem cell transplantation (SCT) following four to five cycles of cyclophosphamide (1000 mg/m2), doxorubicin (75 mg/m2) and 5FU (500 mg/m2). Mastectomy was performed a median of 2 months (range 1.5-45) after high-dose chemotherapy and was followed by radiotherapy. Macroscopic and microscopic pathologic complete response rates were respectively 56 and 39%. With a median follow-up of 36 months (range 17-52) 10 patients remain alive free of disease and seven patients have relapsed. Two relapses occurred in the group of patients with pathologic CR and five in the group with residual tumour. These results show that high-dose chemotherapy (HDC) with alkylating agents followed by SCT allows a very high tumour eradication in inflammatory breast cancer, suggesting a possible global benefit in progression-free survival and survival which remains to be demonstrated prospectively.

Adult↗
PubMed1998

[Impact of recent oncogenetic progress on the management of high risk breast cancer patients: the example of BRCA1 and BRCA2 genes].

Evidence is mounting that hereditary breast cancers and sporadic cases harbor distinct clinical and morphological patterns that are thought to be linked to different natural histories. BRCA1-associated breast cancers appear as high grade, poorly differentiated, highly proliferating, and frequently estrogen receptor negative tumors. Surprisingly, despite these features usually associated with a poor outlook, no decrease in the overall survival is observed in hereditary cases. These elements may be of valuable help in the design of strategies in the medical management of cancer prone individuals.

Animals↗