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M Brunet

Publications and source records attributed to M Brunet.

At least 19 recordsLinked to original sources
PubMed1992

Multiparametric prognostic evaluation of biological factors in primary breast cancer.

BACKGROUND: An array of biological features related to tumor cell differentiation status, growth rate, and invasive potential have been identified as potential prognostic factors in breast cancer. We were interested in determining their relative importance in predicting patient survival. PURPOSE: We evaluated the relative weight of the following four biological factors in predicting survival of patients with breast cancer: tumor cell DNA content (determined by flow cytometry), tumor cell proliferation rate (determined by thymidine kinase activity), expression levels of cathepsin D and urokinase plasminogen activator, and several "classical" clinical and histological factors. METHODS: Selected from a prospectively updated database, the study population consisted of 319 primary breast cancer patients who received treatment and follow-up care (median, 6 years) in the Centre René Huguenin. To determine the profile of biological factors for each patient, we used frozen tumor specimens and (except for the flow cytometric DNA content assay) commercially available assay kits. We determined by Cox multivariate analysis the relationships of the biological factors to each other, to classical prognostic factors, and to disease-free and metastasis-free survival. RESULTS: In the overall population, disease-free survival was best predicted by node status (P = .004), clinical tumor size (P = .02), and cathepsin D expression (P = .01), whereas metastasis-free survival was best predicted by node status (P = .0004), clinical tumor size (P = .009), and urokinase plasminogen activator expression (P = .04). In node-negative patients, thymidine kinase activity was the only factor selected for disease-free (P = .04) and metastasis-free (P = .05) survival. In node-positive patients, the number of positive axillary lymph nodes was the only factor selected for disease-free (P = .0008) and metastasis-free (P = .00017) survival. CONCLUSIONS: Our retrospective analysis has identified protease expression and tumor cell proliferation rate as important biological prognostic factors in breast cancer. Prospective clinical trials should be undertaken to confirm these results.

Adult↗
PubMed1992

Enzyme-linked immunosorbent assay of pS2 in breast cancers, benign tumors, and normal breast tissues. Correlation with prognosis and adjuvant hormone therapy.

An enzyme-linked immunosorbent assay using monoclonal and polyclonal antibodies against recombinant pS2 was devised. It was used to measure pS2 concentration in the cytosol of 339 breast cancer, 15 fibroadenomas, 16 cases of benign breast disease, and 6 normal breast tissues. The mean value of pS2 concentration was higher in cancer, but the protein could be detected readily in benign tumors and even in normal breast. The concentration of pS2 was significantly lower in postmenopausal women and tumors of differentiation Grade 3. The pS2 concentration was correlated strongly with the presence of estrogen receptors (ER) and progesterone receptors (PR). No correlation was observed with the size, histologic type of the tumor, and lymph node status. The prognostic value of pS2 appeared relatively limited. It was clear cut only for a relatively small group of patients (approximately 15%), who had low concentrations of pS2 (less than or equal to 0.32 ng/mg of protein). These patients had a shorter disease-free interval and overall survival time. The most striking correlation was observed with the outcome of adjuvant hormone therapy. pS2 concentration was shown to be the most potent prognostic factor, preceding even ER.

Adult↗
PubMed1991

[Cancer of the ovary after cancer of the breast. 45 cases].

Forty-five patients who had primary cancer of the breast had a laparotomy when a second cancer appeared in the ovaries. There were no other peritoneal metastases to suggest that it was disseminated breast cancer. Twenty-eight had primary ovarian cancer and 17 metastases from breast cancer. The study comparing the two groups shows that: there are few clinical or paraclinical features that make it possible to arrive at a differential diagnosis; ovarian metastases occurring in patients who have primary breast cancer carry a more serious prognosis; if the cancer is a primary ovarian cancer (and not a secondary) the chances of survival are less poor; in primary ovarian cancer the results justify our attitude for carrying out surgery; screening systematically for ovarian involvement by using CA 125 or by routine ultrasound does not seem to us to be effective.

Adult↗
PubMed1990

Predicting distant metastases in operable breast cancer patients.

Risk factors for distant metastases following mastectomy and axillary node dissection for breast cancer were analyzed in a review of 1022 women. From diagnosis until the end of the adjuvant treatment, six stages were identified that corresponded well to patient data acquisition. At each stage, a prognosis study based on the Cox model was carried out using all acquired information from the first stage. The results demonstrated that tumor size, nuclear pleomorphism, mitotic index, and nodal status at the top of axilla were stable independent risk factors in predicting metastasis-free survival (MFS). These analyses also revealed those factors that were significantly related to MFS at one or several stages and losing their significance at a subsequent stage. This was the case with clinical node status, age, and vascular tumor emboli. Other factors such as estrogen, progesterone, histologic grade, and clinical stage were never identified as independent factors at any stage. The four major stable risk factors were used to define a stratification of reference. The results demonstrated that the mere knowledge of clinical information such as tumor size, clinical node status, and age would enable 51% of the patients to be universally well classified according to that stratification. Knowledge of additional factors, such as nuclear pleomorphism and mitotic index, would bring the rate up to 61%, and then to 64% if supplementary information such as vascular tumor emboli were acquired. These percentages did not appear high enough to claim that the physician may make a reliable prognosis of operable breast cancer patients before acquiring information from the axillary node dissection. However, it was proven that there exist some subsets of patients with stable prognosis, i.e., subsets of patients who will belong permanently to the same risk group through the stages.

Adult↗
PubMed1990

[Epidemiologic and prognostic factors of cancer of the breast].

Breast cancer is the most common of all cancers affecting women in France; its frequency increases in countries with a high standard of living. A family history and certain types of mastosis are unquestionable risk factors, although their weight has not yet been well established, but there is no absolute proof that feeding habits (notably fats and alcohol), which have been blamed by some authors, play a role in the genesis of breast cancer. Among the classical prognostic factors, which are necessary for surgical decisions, the size of the tumour, its histological grade and above all the number of axillary lymph nodes involved are the most important. However, a better knowledge of breast cancer biology has yielded factors that seem to be more promising than hormonal receptors, notably the DNA content of tumoral cells and the presence or absence of a protease, procathepsin 52 K, which reflects tumoral aggressiveness. As for the study of oncogens described elsewhere in this monograph, it will provide a better definition of high risk subjects and more precise information on the progress of the cancer.

Adenocarcinoma↗
PubMed1990

Epidermal growth factor receptors and prognosis in primary breast cancer.

A retrospective study was performed on 109 human breast tumors stored in liquid nitrogen in order to assess the prognostic value of epidermal growth factor receptor (EGF-R) (median patient follow-up 5 years). A significant inverse relationship was observed between EGF-R and both estrogen (ER) and progesterone receptors (PR). Univariate analysis showed a trend towards a shorter metastasis-free survival both in the overall population and in node-negative patients with EGF-R positive tumors. Multivariate analysis of the overall population showed that lymph-node involvement and PR status were the only significant variables in predicting metastasis-free survival. However, in patients receiving no adjuvant treatment (hormone therapy or chemotherapy). EGF was the only significant variable in the multivariate Cox analysis. No c-erbB-1 amplification was detected in these tumors.

Adult↗
PubMed1990

Survival effect of systemic therapy on patients developing metastatic breast carcinoma.

A multivariate analysis was performed to assess the effect of post-relapse systemic therapy on a series of patients with metastatic breast cancer who at initial presentation had no detectable metastases (Mo), were less than or equal to 70 years of age, presented with unilateral localized disease and no other associated malignancy, and were treated between 1965 and 1984 with successive protocols for primary disease and subsequently developed distant metastasis. All 760 patients analyzed relapsed with at least one metastasis, and were studied retrospectively with no selection criteria according to any specific protocol. All had recorded clinical data on menopause, stage, clinical tumor aggressiveness (PEV), initial chemo or hormonal therapy, and time to relapse, and had ongoing follow up at our Center, with salvage chemotherapy and/or hormonal therapy having been given to some but not all patients. A brief metastasis-free survival (p less than 0.000001), and factors associated with electing pre-relapse chemotherapy (p less than 0.000001) were associated with shortened post-relapse survival, while post-relapse therapy (chemo p less than 0.0001, and hormonal p less than 0.00001, replacing chemotherapy in the model) apparently increased post-relapse survival in the group overall. This result was similar in the inoperable patient group [with inflammatory breast carcinoma an additional risk factor (p less than 0.0005)], as well as the operable group. However, in the operable group, when the pathologic criteria of histologic grade and nodal status were introduced into the analysis, post-relapse therapy was not seen to be an important factor for survival in any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The concentration of glucose in the culture medium determines the effect of suramin on the growth and differentiation of the human colonic adenocarcinoma cell clone HT29-D4.

Suramin, a drug currently used for advanced malignancy, induces the differentiation of the human colonic adenocarcinoma cell clone HT29-D4 and this process is correlated with a decreased glycolytic activity. We investigated the effects of suramin on HT29-D4 cells in the presence of various glucose concentrations. The main result of this study is that suramin has only an effect on HT29-D4 cell growth and differentiation when the concentration of glucose is above 10 mM. Therefore the efficiency of suramin as an anticancer drug may be greater on poorly differentiated tumoral cells with a high proliferative capacity.

Adenocarcinoma↗
PubMed1990

[Long-term results of radio-surgical treatment of operable carcinoma of the cervix uteri].

Four hundred and fifteen women, treated in our institution from 1961 to 1987 for operable carcinoma of the cervix stage I or II, had a radical hysterectomy with pelvic node dissection. Radiotherapy was associated with this surgery in most cases: 90% of the patients received endocavitary radiation, and 30% external radiotherapy, either pre- or post-operatively, in the case of bad prognostic factors. Median follow up was 7 years; overall survival was 77% at 10 years; the rate of local failure is low (36 cases/415 = 8.7%). Multifactorial analysis, using the Cox model, assessed the following independent prognostic factors, significant for the risk of local recurrence (size of the tumor, N +/- , FIGO stage) and for the risk of metastases and death (parametrium invasion, stage, tumor size). Post-operative mortality was 1.2%. Early surgical iatrogeny was easily treated with no long-term sequela, whereas severe complications, due to the association with pelvic irradiation, occurred in 24 out of 124 patients, leading to 7 "illegitimate" deaths.

Adult↗
PubMed1989

Cathepsin D: an independent prognostic factor for metastasis of breast cancer.

122 patients with primary breast cancer were followed-up for a median of 4.6 years after surgery. The concentration of cathepsin D in tumour cytosol was strongly related to both metastasis-free survival and disease-free survival and was independent of nine conventional prognostic indices. Cathepsin D assay may prove particularly useful in identifying women who, though without lymph node involvement at presentation, are at high risk of metastatic disease.

Adult↗
PubMed1989

Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas.

We did a multivariate analysis of 1262 patients with operable, invasive ductal breast carcinoma to assess the prognostic value of the Scarff-Bloom-Richardson (SBR) histologic grading system. Nodal metastasis and SBR were the two most important factors for metastasis-free survival (MFS), P = 10-9 and P = 10-5, respectively, for total study time. In patients who were node negative, the SBR and International Union Against Cancer (UICC) stages were the most important for MFS (P = 4 X 10-4 and P = 0.03). In order to try to improve the SBR prognostic value, we first studied the three components of the SBR separately: ductoglandular differentiation proved the least predictive and nuclear pleomorphism and mitotic index the most predictive. A rearrangement of the two nuclear scores alone produced higher risk values and better risk separation of patient subpopulations than SBR, and eliminated the SBR from the multivariate model. This rearrangement, modified SBR (MSBR), defined five new risk subgroups with statistically different risk ratios for MFS (P = 3 X 10-8). SBR grade II (55% of patients) was separated into three MSBR groups significantly different according to MFS (P = 0.008). In the patients who were node negative, MSBR replaced the SBR and was the most important factor for prediction of relapse of MFS (P less than 0.00001). The MSBR is more accurate and predictive than the standard SBR grade and is particularly useful when the nodal status of the patient is negative or unknown.

Adult↗
PubMed1989

Nuclear characteristics as indicators of prognosis in node negative breast cancer patients.

Nine clinical, biologic and histologic variables were evaluated for their significance in predicting the metastasis free survival (MFS) and the overall survival (OS) of 650 histologic node negative breast cancer patients. The variables studied were: menopausal status, UICC clinical stage of disease, Scarff-Bloom and Richardson (SBR) grade and its 3 components, estrogen and progesterone receptors, and anatomic tumor size. Multivariate Cox analyses revealed that histologic grade and clinical stage were the only significant prognostic factors for both MFS and OS. In the SBR grading system, grades I and III clearly have defined those patients with low and high risk for relapse, respectively. However, it is well known that more than 50% of the patients fall into the intermediate risk category, grade II, which provides essentially no useful prognostic information for those patients. To improve the assignment of patients to specific risk groups, a modified grade (MSBR), with five categories ordered according to the degree of malignancy, has been built from the nuclear pleomorphism and the mitotic index of the SBR grade. In combination with clinical stage, MSBR was found to be a prognostic indicator with high discriminatory power and caused the SBR grade to lose its significance. The first three categories of this MSBR may be gathered to designate low risk patients, whereas the last two categories, once combined, contain all the SBR grade III plus 57% of the SBR grade II tumors, and reliably identify high risk node negative patients. We suggest that a systemic adjuvant therapy should be discussed in this high risk group.

Adult↗
PubMed1989

Prognostic value of estrogen and progesterone receptors in primary infiltrating ductal breast cancer. A sequential multivariate analysis of 1262 patients.

Nine prognostic variables were evaluated for their significance in predicting the overall survival (OS), the length of disease-free survival (DFS) and the length of metastasis-free survival (MFS) of 1262 patients with primary breast cancer. The variables studied were: UICC clinical stage; menopausal status; histologic grade; number of involved nodes; anatomic tumor size; estrogen and progesterone receptors; local and adjuvant therapies. Three sequential multivariate analyses, at 2, 5 and 10 years, using the Cox proportional hazard regression model, were carried out to identify those variables most highly related to the criteria studied (overall, disease-free, metastasis-free survivals) and especially to fully evaluate the effects of hormonal receptors on prognosis and their stability over time. Our results showed that number of involved nodes and histologic grade were the most significant prognostic factors for all periods of time and whatever the criterion studied; ER had no predictive value while PR was an independent prognostic factor for metastasis-free survival at 2 years (P = 0.01) and 5 years (P = 0.02) but lost its significance at 10 years (P = 0.06). In the subgroup of 261 patients who received prolonged post-operative adjuvant chemotherapies, PR was the main prognostic factor for MFS at 2 years (P = 0.03) and the second at 5 years (P = 0.05) just after number of involved nodes. In the 1001 patients who did not receive prolonged post-operative adjuvant chemotherapies ER was significant for MFS at 5 and 10 years. The present data urge the need for a periodic redefinition of prognostic factors in primary breast cancer.

Adult↗
PubMed1989

Comparison of the efficacy of propranolol and amiodarone in suppressing ventricular arrhythmias following myocardial infarction.

The purpose of this prospective randomized trial was to compare the efficacy of propranolol and amiodarone in suppressing ventricular arrhythmias during the first 6 months following myocardial infarction (MI). 97 patients were treated with either amiodarone (n = 48) or propranolol (n = 49) starting on the 9th day following MI. Holter monitoring was carried out on four occasions: on D7, D21, D90 and D180. There was no statistical difference in the incidence of 'major' arrhythmias (an average of at least 10 ventricular premature complexes (VPCs) h-1, multiform or paired VPCs or runs) between the two groups on D7. A significant difference in favour of amiodarone became apparent at D180 (P = 0.04). Patients were also classified according to whether treatment failed or was successful. 'Success' was recorded when arrhythmias remained minor or became minor (less than 10 uniform VPCs h-1) and 'failure' when arrhythmias remained major or became major, or when patients were withdrawn because of side-effects, or lost to follow-up. The difference remained in favour of amiodarone (P = 0.03 at D21; P = 0.05 at D90; P = 0.06 at D180). Evaluation of the percentage reduction in the number of VPCs at D21, D90 or D180 compared with D7 showed superiority of amiodarone at D90 (P less than 0.01) and D180 (P less than 0.04). In this study, the overall effect of amiodarone on ventricular arrhythmias following MI was shown to be superior to that of propranolol.

Aged↗
PubMed1989

[Comparative efficacy of amiodarone and propranolol on ventricular arrhythmia in the post-infarction period].

Beta-blockers are known to be effective against post-infarction ventricular arrhythmias and amiodarone has recently been shown to have this property. The purpose of this prospective randomized study was to compare the effects of beta-blockers and amiodarone during the first 6 months following infarction. Nine days after the onset of myocardial infarction, 97 patients were put on either amiodarone (48) or propranolol (49). Holter monitoring was performed on four occasions: on the 7th post-infarction day (baseline), then on the 21st, 90th and 180th days (under treatment). On D7 the two groups were similar in age, sex, risk factors, medical history, characteristics of the infarction and type of arrhythmia. For result analysis purposes the patients were divided into two categories depending on whether their arrhythmia was "moderate" (less than 10 monomorphous and isolated ventricular extrasystoles per hour) or "severe" (at least 10 ventricular extrasystoles per hour, or polymorphous or repetitive ventricular extrasystoles). Concerning the frequency of "severe" arrhythmia, there was no statistical difference between the two treatment groups on D7 (p = 0.53), but differences in favour of amiodarone became increasingly important during the study (p = 0.08 on D21; p = 0.07 on D90; p = 0.04 on D180).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

[Percutaneous transluminal atherectomy of the femoropopliteal arteries. Technic, indications, results after 6 months].

Percutaneous atherectomy was performed in 25 patients with 30 symptomatic femoro-popliteal stenoses. Twenty-three patients were successfully treated with resolution of claudication and a mean 0.35 increase in the ankle-arm-index. Two early thromboses occurred. Residual stenosis was less-than 30% in 25 lesions, with no dissection, and no embolization. Atherectomy seems to be an effective treatment for eccentric and calcified lesions. At 6 months follow-up (17 patients, 19 lesions) clinical and Doppler improvement remained stable in 14 patients; 2 restenosis and 1 new disease occurred. Atherectomy restores a large lumen with minimal wall trauma, thereby possibly decreasing the restenosis rate.

Adult↗