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A Fourquet

Publications and source records attributed to A Fourquet.

At least 37 records · Page 2Linked to original sources
PubMed2001

Comparative image and flow cytometric TUNEL analysis of fine needle samples of breast carcinoma.

The assessment of apoptosis in solid tumors is of interest because of its biological role in tumor evolution and response to therapy. A commonly used method for apoptosis measurement is the TUNEL 3' end-labeling technique, which has shown wide variations in results when applied to solid tumors. Thirty-one fine needle breast carcinoma samples were analyzed by fluorescent TUNEL assay and DNA content using image analysis and flow cytometry. TUNEL positivity, seen both in cells with apoptotic morphology and in a subset of morphologically normal cells, was categorized into five staining patterns and quantitated. Values for patterns of TUNEL-positive cells were compared with TUNEL positivity measured by flow cytometry. Flow cytometric quantitation showed a mean of 24.3% positive cells, which correlated (P < 0.02) with total positive cells (all patterns) measured by image (22.4%). Image analysis quantitation of morphologically apoptotic cells (4.2%) did not correlate with flow cytometric TUNEL positivity and the majority of TUNEL-stained cells were morphologically normal (17%). Image analysis allows discrimination of TUNEL-positive morphologically apoptotic and nonapoptotic cells, which are included in the total number of TUNEL-positive events measured by flow cytometry.

Apoptosis↗
PubMed2001

Salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ of the breast.

BACKGROUND: The purpose of the current study is to evaluate the outcome of salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. METHODS: An analysis was performed of 42 patients with local only first failure (n = 41) or local-regional only first failure (n = 1) after breast-conserving surgery and radiation treatment had been given for DCIS of the breast. Surgical treatment at the time of local recurrence included mastectomy (n = 37; 88%) or excision (n = 5; 12%). Adjuvant systemic therapy at the time of local recurrence was chemotherapy (n = 3; 7%), tamoxifen (n = 8; 19%), both (n = 1; 2%), none (n = 29; 69%), or unknown (n = 1; 2%). The median interval from the time of initial treatment to local recurrence was 4.8 years (range = 1.0-15.2 yrs). The median follow-up after salvage treatment was 4.5 years (range = 0.2-12.8 yrs). RESULTS: At the time of the local recurrence, 22 patients (52%) had invasive ductal carcinoma, 18 patients (43%) had DCIS, 1 patient (2%) had invasive lobular carcinoma, and 1 patient (2%) had angiosarcoma. After salvage treatment, the rate of overall survival and the rate of cause specific survival for all 42 patients were 92% at both 5- and 8-years after treatment. The rate of freedom from distant metastases was 89% at 5 and 8 years. Favorable prognostic factors after salvage treatment were DCIS as the histology of the local recurrence and mammography only as the method of detection of the local recurrence. CONCLUSIONS: The results of salvage treatment in the current study demonstrated that local recurrences were salvaged with high rates of survival and freedom from distant metastases. These results support the use of breast-conserving surgery and radiation for initial management of DCIS of the breast.

Adult↗
PubMed2001

Phytoestrogens after breast cancer.

The current extension of the indications for adjuvant chemotherapy, which predisposes to early menopause, and the media coverage of the benefits of hormone replacement therapy (HRT) have led patients with a history of breast cancer to seek treatments for estrogen deprivation. In breast cancer survivors, most physicians avoid HRT because of concern regarding the potential promotion of growth of occult malignant cells by estrogens, due to the estrogen dependence of breast cancer. Soy phytoestrogens are being promoted as the 'natural alternative' to HRT and have been available without restrictions for several years as nutritional supplements. In this paper, data on the complex mammary effects of phytoestrogens in epidemiological studies, in in vitro studies, as well as in in vivo studies on animal carcinogenesis are reviewed. The potential benefits and risks of phytoestrogens are analyzed, and the prescription of phytoestrogens to postmenopausal women after breast cancer and the coprescription with the anti-estrogen tamoxifen are discussed. The absence of controlled trials and technical checking of extraction and titration in these preparations on 'free sale' raise a new problem in terms of public health and justify close reasoning and a cautious attitude of physicians, as well as straight information given to women, especially after breast cancer.

Animals↗
PubMed2000

Familial invasive breast cancers: worse outcome related to BRCA1 mutations.

PURPOSE: Although all studies confirm that BRCA1 tumors are highly proliferative and poorly differentiated, their outcomes remain controversial. We propose to examine, through a cohort study, the pathologic characteristics, overall survival, local recurrence, and metastasis-free intervals of 40 patients with BRCA1 breast cancer. PATIENTS AND METHODS: A cohort of 183 patients with invasive breast cancer, treated at the Institut Curie and presenting with a familial history of breast and/or ovarian cancer, were tested for BRCA1 germ-line mutation. Tumor characteristics and clinical events were extracted from our prospectively registered database. RESULTS: Forty BRCA1 mutations were found among the 183 patients (22%). Median follow-up was 58 months. BRCA1 tumors were larger in size (P =.03), had a higher rate of grade 3 histoprognostic factors (P =.002), and had a higher frequency of negative estrogen (P =.003) and progesterone receptors (P =.002) compared with non-BRCA1 tumors. Overall survival was poorer for carriers than for noncarriers (5-year rate, 80% v 91%, P =.002). Because a long time interval between cancer diagnosis and genetic counseling artificially increases survival time due to unrecorded deaths, the analysis was limited to the 110 patients whose diagnosis-to-counseling interval was less than 36 months (19 BRCA1 patients and 91 non-BRCA1 patients). The differences between the BRCA1 and non-BRCA1 groups regarding overall survival and metastasis-free interval were dramatically increased (49% v 85% and 18% v 84%, respectively). Multivariate analysis showed that BRCA1 mutation was an independent prognostic factor. CONCLUSION: Our results strongly support that among patients with familial breast cancer, those who have a BRCA1 mutation have a worse outcome than those who do not.

Adult↗
PubMed2000

The influence of patient, tumor and treatment factors on the cosmetic results after breast-conserving therapy in the EORTC 'boost vs. no boost' trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups.

PURPOSE: To analyze the influence of different patient, tumor, and treatment parameters on the cosmetic outcome after breast-conserving therapy at 3-year follow-up. A subjective and an objective cosmetic scoring method was used and the results of both methods were compared. PATIENTS AND METHODS: In EORTC trial 22881/10882, 5569 early-stage breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential fields irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. A total of 5318 patients, having a microscopically complete tumorectomy, were randomized between no further treatment and a boost of 16 Gy to the primary tumor bed. The cosmetic result at 3-year follow-up was assessed by a panel for 731 patients, and by digitizer measurements, measuring the displacement of the nipple, for 1141 patients. Univariate and multivariate analyses were used to evaluate the correlation between various patient, tumor, and treatment factors and cosmesis. RESULTS: The factors associated with a worsened cosmesis according to the panel evaluation were: an inferior tumor location, a large excision volume, the presence of postoperative breast complications, and the radiotherapy boost. According to the digitizer measurements, a central/superior tumor location, a large excision volume, an increased pathological tumor size, an increased radiation dose inhomogeneity, and an increased bra cup size resulted in an increased asymmetry in nipple position. It appeared that the evaluation of the nipple position (whether by panel or by digitizer) is only moderately representative of the overall cosmetic outcome. CONCLUSION: To achieve a good cosmesis, it is necessary to excise the tumor with a limited margin, to avoid postoperative complications, to assess the need for a boost in the individual patient, and to give the radiation dose as homogeneously as possible. As far as the method of evaluation is concerned, the panel evaluation is the most appropriate method for giving an overall impression of the cosmetic result after breast-conserving therapy (BCT). The use of the digitizer is recommended for comparing the cosmetic outcome of two different approaches to BCT or for analyzing cosmetic changes over time.

Adult↗
PubMed2000

ERBB2 overexpression in breast carcinomas: no positive correlation with complete pathological response to preoperative high-dose anthracycline-based chemotherapy.

The predictive value of ERBB2 amplification/expression to doxorubicin use is controversial. Preoperative chemotherapy, followed by the pathological assessment of tumour response to treatment provide optimal conditions for the evaluation of the predictive value of biological parameters. We report here data on the predictive value of ERBB2 in a series of 54 cases of breast cancer treated by preoperative high-dose anthracycline-based chemotherapy. Our series consisted of 26 women presenting an inflammatory breast cancer (IBC) and of 28 women with poor prognosis primary cancer (PPPC). Patients received a total of four cycles with doxorubicin (75 mg/m(2) for IBC or 70 mg/m(2) for PPPC) and cyclophosphamide (6 g/m(2) for IBC or 1400 mg/m(2) for PPPC), every 21 days. ERBB2 expression was determined by immunohistochemistry (clone CB11) performed on a tumour biopsy taken before chemotherapy. All patients underwent surgery as a second step of treatment, and the tumour response was assessed on pathological specimens. A complete pathological response was observed in 24 of the 54 cases (44%) (95% confidence interval (CI), 31-57). Pathological complete response was positively correlated with high histological grade (P=0. 02) and with the absence of oestrogen (P=0.003) or progesterone (P=0. 02) receptor expression. ERBB2 overexpression was found in 18 of the 54 cases (33%). A complete pathological response was observed in 33% of these cases (6/18). This figure was not significantly different from the 50% rate of complete response observed for tumours with no detectable ERBB2 expression (18/36). In this small series, ERBB2 overexpression was not a significant predictive marker of the pathological response to high-dose doxorubicin-based chemotherapy.

Adult↗
PubMed2000

Low expression of bcl-2 in Brca1-associated breast cancers.

Little data are available concerning the molecular mechanisms of action of Brca1 and Brca2 in breast oncogenesis. Recent experimental results suggest that Brca1 plays a role in the regulation of apoptosis. In order to determine whether the analysis of human tumours would provide data supporting this hypothesis, we have assessed the expression of the antiapoptotic bcl-2 and of the proapoptotic p53 genes in Brca1 - and Brca2 -associated breast carcinomas. The levels of expression of these genes were compared to those observed in controls and to the mitotic and the apoptotic indexes. Our series were composed of 16 cases of breast carcinoma in women with a germline Brca1 gene mutation, and of four cases with Brca2 mutation. A group of 39 patients aged under 36 years and for whom the search for Brca1 gene mutations was negative, and a group of 36 cases of sporadic cancers without data on their Brca status were used as controls. Immunohistochemistry was used to detect p53 and bcl-2 gene products. Mitotic and apoptotic indexes were higher in Brca1 -associated tumours than in controls. No significant difference in p53 immunostaining was observed between the four groups of patients. In contrast, the rate of bcl-2 -positive tumours was lower (31%) in Brca1 -carcinomas than in carcinomas without Brca1 mutation (90%) (P< 10(-3)). A strong Bcl-2 expression was found in the four cases of Brca2 -associated carcinomas. No significant correlation was observed between p53 and Bcl-2 immunostainings, either in cases or in controls. The association between Brca1 status and Bcl-2 expression remained significant after adjustment for the oestrogen receptor status. Our study shows that a low expression of bcl-2 characterises most Brca1 -associated breast carcinomas, a biological trait which seems not to be shared by Brca2 -associated tumours nor to be related to oestrogen receptor and/or p53 status. bcl-2 might thus be one of the target genes involved in the oncogenesis related to Brca1 and its down-regulation may account for the increased apoptosis and the high proliferative rate observed in Brca1 -associated carcinomas.

Adult↗
PubMed2000

LMCE3 treatment strategy: results in 99 consecutively diagnosed stage 4 neuroblastomas in children older than 1 year at diagnosis.

PURPOSE: To tailor postinduction therapy for stage 4 neuroblastoma in children who are older than 1 year at diagnosis according to status after induction. PATIENTS AND METHODS: From March 1987 to December 1992, 99 patients who were consecutively admitted were included in the Lyon-Marseille-Curie East of France (LMCE)3 strategy. After induction with the French Society of Pediatric Oncology NB87 regimen and surgery, patients who were in complete remission immediately proceeded to consolidation therapy with vincristine, melphalan, and fractionated total-body irradiation (VMT). All other patients underwent a postinduction strategy before VMT, either an additional megatherapy regimen or further chemotherapy with etoposide/carboplatin. RESULTS: The progression-free survival (PFS) is 29% at 7 years from diagnosis, which compares favorably with that of a similar cohort of 72 patients previously reported by our group (LMCE1; PFS of 20% at 5 years and 8% at 14 years, P =.004). In the multivariate analysis, only age younger than 3 years at diagnosis (P =.0085) and achievement of complete or very good partial remission after NB87 and surgery (P =.00024) remained significant. The PFS of the 87 patients who were included in the postinduction strategy was significantly better than that of the comparable 62 patients on the LMCE1 study (32% v 11% at 7 years; P =.005). CONCLUSION: The progressive improvements in the LMCE results over the last 10 years suggest that improvements in supportive care measures and increases in each component of this strategy (induction, postinduction, consolidation) may all contribute to increased survival rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Standards, Options and Recommendations (SOR) for endocrine therapy in patients with non metastatic breast cancer. FNCLCC].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for endocrine therapy in patients with non metastatic breast cancer. METHODS: Data have been identified by literature search using Medline, Embase, Cancerlit and Cochrane databases - until july 1999 - and the personal reference lists of the expert group. Once the guidelines were defined, the document was submitted for review to 125 independent reviewers. RESULTS: The main recommendations for the endocrine therapy of patients with non metastatic breast cancer are: 1) Endocrine therapy modalities depend on menopausal status or age of women: ovarian suppression for premenopausal women, antiestrogen drug therapy for postmenopausal women (standard). 2) Tamoxifen (20 mg/d - 5 years) is beneficial to women with positive estrogen receptor tumor (standard, level of evidence A). There is no indication of tamoxifen treatment for women with negative estrogen receptor tumor (standard, level of evidence A). 3) For postmenopausal women with positive estrogen receptor tumor, tamoxifen is the standard adjuvant treatment (level of evidence A). For postmenopausal women with negative estrogen receptor, adjuvant chemotherapy has to be considered (option, level of evidence A). No adjuvant treatment has to be considered for women with poor health condition (option). 4) For premenopausal women with estrogen receptor tumor, results of clinical trials of chemotherapy versus endocrine therapy, suggest a benefit for endocrine therapy. However, there is no sufficient evidence to consider endocrine therapy alone as a standard adjuvant treatment. 5) For premenopausal women, chemotherapy + ovarian suppression or chemotherapy + tamoxifen are not better than chemotherapy alone (level of evidence A). 6) For postmenopausal women, administration of chemotherapy plus adjuvant tamoxifen versus the same tamoxifen alone, is of additional benefit in reducing recurrences but not in prolonging overall survival (standard, level of evidence A). 7) Balance of known benefits (delay to recurrence and death) and risks (side-effects of therapy) for adjuvant chemoendocrine therapy has to be taken into consideration before decision making. Chemoendocrine therapy can be indicated for women at high risk of developing metastatic disease (recommendation, experts agreement).

Antineoplastic Agents, Hormonal↗
PubMed2000

[Radiotherapy of cancer of the breast. Technical problems and new approaches].

Technical problems often arise during irradiation to the breast, chest wall, and regional lymph nodes. The following are among the most frequently encountered problems: avoidance of normal tissues (heart and lungs) during chest wall, internal mammary nodes, and large breast irradiations; dose heterogeneity in large breasts; under- or overdosage at field junctions (breast medial tangent and internal mammary fields in particular). Various technical solutions have been offered: modified treatment positions, field inclinations, and conformal irradiation. Many are currently under evaluation. These new technical approaches in breast cancer irradiation require modern facilities for imaging, simulation, and dosimetry, which help to individually design treatment planning.

Breast Neoplasms↗
PubMed1999

The influence of the boost in breast-conserving therapy on cosmetic outcome in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer.

PURPOSE: To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy (BCT). METHODS AND MATERIALS: In EORTC trial 22881/10882, 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. Patients having a microscopically complete tumor excision were randomized between no boost and a boost of 16 Gy. The cosmetic outcome was evaluated by a panel, scoring photographs of 731 patients taken soon after surgery and 3 years later, and by digitizer measurements, measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later. RESULTS: There was no difference in the cosmetic outcome between the two treatment arms after surgery, before the start of radiotherapy. At 3-year follow-up, both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result. The panel evaluation at 3 years showed that 86% of patients in the no-boost group had an excellent or good global result, compared to 71% of patients in the boost group (p = 0.0001). The digitizer measurements at 3 years showed a relative breast retraction assessment (pBRA) of 7.6 pBRA in the no-boost group, compared to 8.3 pBRA in the boost group, indicating a worse cosmetic result in the boost group at follow-up (p = 0.04). CONCLUSIONS: These results showed that a boost dose of 16 Gy had a negative, but limited, impact on the cosmetic outcome after 3 years.

Adult↗
PubMed1999

Longitudinal clinical and functional pulmonary follow-up after megatherapy, fractionated total body irradiation, and autologous bone marrow transplantation for metastatic neuroblastoma.

BACKGROUND: A prospective follow-up was undertaken to document longitudinal changes in lung function in children with neuroblastoma treated with the Lyon-Marseille-Curie-East of France Group protocol, consisting of high-dose chemotherapy schedules in combination with total body irradiation (TBI) and autologous bone marrow transplantation (ABMT), to determine the extent and timing of any changes seen and to describe late clinical and functional pulmonary sequelae. PROCEDURES: Eighteen children (1.5-6.9 years of age at TBI) performed pulmonary function tests (PFTs). These included measurement of functional residual capacity (FRC) to assess lung growth and dynamic lung compliance (CLdyn) and lung transfer factor for CO (TLCO) for evaluation of distal bronchi and/or interstitial abnormalities. RESULTS: The clinical follow-up showed that bronchopulmonary symptoms occurred in 12 children. Three of them were clinically severely incapacitated. Serial PFTs showed an initial decrease of all mean values 6 months after TBI, with improvement in mean values of FRC and TLCO at 1 year. Thereafter, a significant decrease of mean FRC and CLdyn was observed from 2 years to 4 years after TBI with preservation of TLCO, suggesting restrictive ventilatory defects rather than pulmonary fibrosis. Individual analysis showed PFT defects in 100% of children 4 years after TBI. There was a higher incidence of lung pathology after two blocks of high-dose chemotherapy than after one block (100% versus 40%) and more severe sequelae. However these children had residual disease present after induction associated with lower baseline PFT. CONCLUSIONS: PFT defects were found in all children 4 years after TBI-ABMT, but they remained within acceptable limits except in very young children.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Analyzing prognostic factors in breast cancer using a multistate model.

In breast cancer clinical research, an important goal is to analyze how factors are seen to affect the disease process. Meanwhile, the disease progression is not fully modelled using standard analysis since transitions between intermediate events such as local-regional recurrences (LRR) or metachronous contralateral breast cancer (MCBC) are not considered. In the present study, the progression of disease was modelled using a multistate model. By this approach, we assessed transitions during the course of the disease and studied prognostic factors for each transition. The model was applied to 6,185 patients with unilateral ductal invasive breast cancer, clinical stage I through III, treated between 1981 and 1988 at the Curie Institute. At first diagnosis, high clinical stage, high histological grade, positive lymph nodes, and age less than 40 years were associated with increased risks of LRR, metastases, or death. Except age, the same factors remained predictive for metastases or death following LRR. Chemotherapy for the first cancer was associated with a decreased risk for developing MCBC. As the time interval from diagnosis of the primary tumor to that of a local or contralateral recurrence increased, the risk of metastases or death decreased. Nodal status for the first tumor and clinical stage for the contralateral tumor increased the risk of metastases or death following MCBC. Conversely, the risk decreased for patients who received adjuvant hormone therapy following MCBC. In conclusion, the multistate model offers us a much more appropriate way to study prognostic factors for each transition in breast cancer disease.

Adult↗
PubMed1999

Short and long-term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomized trial.

A potential advantage of primary over adjuvant chemotherapy in breast cancer survival had been proposed on theoretical grounds. In 1994, early results of the S6-trial comparing primary chemotherapy vs. adjuvant chemotherapy for operable breast cancer in 390 premenopausal patients had shown significant improvement in survival of the primary chemotherapy arm (p = 0.04). An updated analysis conducted in 1995 showed the disappearance of this difference between the two arms (p = 0.18). In the present analysis, we investigated the potential short and long-term benefits attributable to primary chemotherapy by applying weighted logrank tests designed to assess specifically these effects. Results were compared to those obtained with the classical logrank test. At a median follow-up of 105 months, a significant short-term survival benefit (p = 0.02) in favor of the primary chemotherapy has been shown. However, no long-term survival benefit (p = 0.36) could be documented. The classical logrank test had revealed no significant difference (p = 0.24) between the two groups but the proportional hazard assumption being rejected (p = 0.04), the efficiency of this test can be questioned. Results using the present analysis suggested that primary chemotherapy delayed early death rates, without significantly modifying long-term event rates. It emphasizes that a short-term effect which is not necessarily associated with a long-term benefit may be seen at an early evaluation and disappear later on.

Antineoplastic Agents↗
PubMed1999

Radiation dose homogeneity in an EORTC multicenter trial on breast irradiation.

The influence of the radiation dose on local control and cosmetic outcome in breast-conserving treatment for breast cancer is investigated in EORTC trial 2288110882. In this study 50 Gy is administered to the whole breast, and the effect of an additional dose to the tumor-bearing area (boost dose) is evaluated. The purpose of this analysis is to document the dose homogeneity of the radiation dose as reported in the first 1915 treatment forms, received at the EORTC Data Center. The dose to the prescription Point (A) was within 95 and 110% of 50 Gy in all but 13 (99.3%) patients (median dose 50 Gy) and the minimum and maximum doses in the central plane of the breast were within 95% and 110% of the dose to point A in 82% of patients. The dose to the tumor excision area (point B) was within the homogeneity criteria in 97% of patients, and the boost doses were consistent with randomization in 93% of cases. These data, based on one-third of the randomized patients in trial 22881/10882, demonstrate a high level of homogeneity in radiation doses, despite a number of ambiguities in the protocol, which were efficiently clarified a few months after the beginning of the trial. This high level of consistency is a remarkable achievement given the number of centers, the number of patients, and the number of countries involved in this trial.

Adult↗