Biomedical subjects

K Hacene

Publications and source records attributed to K Hacene.

At least 37 records · Page 2Linked to original sources

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

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

[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↗

PubMed1987

[An expert system of aiding decision making in breast pathology connected to a clinical data base].

The René Huguenin Cancer Center holds a medical file for each patient which is intended to store and process medical data. Since 1970, we introduced computerization: a development plan was elaborated and simultaneously a statistical software (Clotilde--GSI/CFRO) was selected. Thus, we now have access to a large database, structured according to medical rationale, and utilizable with methods of artificial intelligence towards three objectives: improved data acquisition, decision making and exploitation. The first application was to breast pathology, which represents one of the Center's primary activities. The structure of the data concerning patients is by all criteria part of the medical knowledge. This information needs to be presented as well as processed with a suitable language. To this end, we chose a language-oriented object, Mering II, usable with Apple and IBM 4 micro-computers. This project has already allowed to work out an operational model.

Breast Neoplasms↗

PubMed1986

Competitive prognostic value of clinicopathologic and bioimmunologic factors in primary breast cancer.

Fourteen clinical, pathologic, and pretreatment bioimmunologic variables were evaluated for their significance in predicting the survival or the length of disease-free interval of 55 patients with primary breast cancer. The variables studied were: patient age; clinical stage of disease according to the International Union Against Cancer TNM classification; number of involved nodes; sedimentation rate; peripheral lymphocyte, leucocyte, and monocyte counts; serum levels of immunoglobulins IgG, IgA, and IgM; percentages of E-, "active" E-, and EAC-rosettes; and finally, the lymphoblastic transformation test value (PHA-LTT). A multivariate analysis using the Cox proportional hazards regression model was carried out, in a stepwise manner, to identify those variables most highly related to survival or to the length of disease-free interval. The Cox analysis showed that clinical stage, number of involved nodes, percentage of EAC-rosettes, sedimentation rate, and T-lymphocyte reactivity, (i.e., the T-lymphocyte sensitivity to PHA, expressed as the ratio between the PHA-LTT in counts per minute and the percentage of E-rosettes) were the significant prognostic factors for survival, whereas the number of involved nodes and the sedimentation rate were independent of importance in predicting the length of disease-free interval. The results obtained from this analysis proved the importance of some immunologic parameters in the estimation of prognosis. In addition, a prognostic score for summarizing multiple factors with potential use in stratification was derived from the multivariate analysis.

Blood Sedimentation↗

PubMed1986

Tissue glycolytic enzymes in primary breast cancer patients receiving adjuvant chemotherapy.

Primary breast cancers from 85 patients undergoing post-surgical adjuvant chemotherapy were analyzed for five glycolytic enzymes: lactate dehydrogenase (LDH); phosphohexose isomerase (PHI); glucose-6-phosphate dehydrogenase (G-6PD); pyruvate-kinase (PK); and 6-phospho-gluconate dehydrogenase (6-PGD). The purpose of this study was to determine whether biochemical parameters could offer a prognostic index to determine outcome of therapy. The patients were followed up to a maximum of 54 months; during this period 30 of them developed recurrent or metastatic disease. The enzyme activities were expressed by the three following reference parameters: units/g proteins, units/g tissue weight and units/mg DNA. Two methods of analysis were compared: firstly, univariate analysis using life tables; and secondly, multivariate analysis using the Cox's model, where enzyme levels were tested for each mode of expression in addition to node status, histological features, receptor and menopausal status. Life table analyses appear limited when subsets of patients were studied because the sample size tends to become too small to warrant firm conclusions. Using the Cox's model, a prognostic index 1 was proposed, including the number of involved nodes and the product of logarithms of G-6PD and 6-PGD expressed as units/mg DNA. Compared to the number of involved nodes, this index gives a slightly better discrimination of the patients at 2 yr after mastectomy.

Adult↗

PubMed1986

Breast cyst fluid proteins and breast cancer.

A specific breast cyst fluid protein was purified by the following steps: ultracentrifugation, gel filtration, DEAE and Con A chromatography, and gel filtration with guanidine, 6 M. The protein was pure, having a molecular weight of 17,800 daltons on SDS-PAGE and 68,000 daltons on gel filtration. The GCDFP 17,800 is immunologically distinct from other breast cyst fluid components and known milk and plasma proteins. A specific radioimmunoassay was developed and used to determine GCDFP 17,800 in 158 samples of breast cancer cytosol. The GCDFP 17,800 levels were significantly different between grade I tumors (mean of 813 ng protein per mg +/- 430 SEM) and grade III tumors (mean 184 ng protein per mg +/- 59 SEM) and were correlated with progesterone receptor values in postmenopausal women (Spearman's correlation, p = 0.03) but not in premenopausal women. The value of GCDFP 17,800 did not differ between the pre- and the postmenopausal women. By immunocytochemistry the intracellular localization of the GCDFP 17,800 was also found in relation to tumor grading and in correlation with PR values. GCDFP 17,800 appears as a hormone-induced protein of the breast cells. Its intracellular detection by means of radiolabeling allows a more sensitive and precise evaluation of the hormone-dependence of the breast cancer cells and emphasizes the heterogeneity of the tumor cell population.

Amino Acids↗

PubMed1985

Immunohistochemistry of a component protein of the breast cystic disease fluid with mol. wt 15,000.

A specific protein from the liquid of a mammary cyst with a molecular weight of 15,000 (GCDFP 15) was studied in normal and pathological mammary tissue using an immunohistochemical method (peroxidase-anti-peroxidase complex). An immunoreactivity of the GCDFP type was found in normal idrosadenoid glands having an apocrine secretion. Histologically normal mammary tissue was not immunoreactive. In benign breast tissue the GCDFP was found particularly in epithelium undergoing apocrine metaplasia (55/55) and in atypical lobular epithelial hyperplasia (8/10). Of the adenocarcinomas of the breast 136/161 (84%) were immunoreactive, especially lobular carcinoma (13/13). The proportion of tumors with a high percentage of immunoreactive cells (76-100%) was greater for Bloom's grade I (1/29: 34%) than for grade III (10/66: 15%). A significant correlation was found between the percentage of immunoreactive cells and the cytosolic concentration of progesterone receptors. The morphological intracellular identification of GCDFP (due to its greater sensitivity) and its correlation with progesterone receptors allowed a more precise evaluation of the functional state and the hormonal dependency of the breast cells by underlining the heterogeneity of the tumoral cell population.

Apocrine Glands↗

PubMed1985

[Cancer of the prostate. Epidemiologic evaluation, incidence, and trends, especially in France].

With 7,172 deaths in 1982, prostatic cancer is a frequent cancer in France observed among old men, coming just after the lungs cancers and representing 9.6% of male mortality from malignant disease. Its incidence in the French regional population based on departmental registries is about 25/100.000 (age adjusted to the world standard population). The geographical distribution throughout the world shows a high incidence rate among the black american, the Scandinavian countries and low rates in the south-east of Asia. As well as incidence as for mortality low trends of increase all over the world are observed. In the clinical data from the "Enquete Permanente Cancer" (E.P.C.) the high proportion of metastatic dissemination (48%) at initial time of diagnosis, and also the high proportion of epithelial cancer (92%) emerge from a series of 1,223 prostatic cancer registered between 1975 and 1982. The 9 year-survival relative rate (32%) for the whole group lets appear a level of cure observed after the 8 years of follow-up. Few risk factors have been yet recognized so that it is not easy to identify risk population and propose them any preventions.

Adenocarcinoma↗

PubMed1984

Immunohistochemical detection of alphalactalbumin in breast lesions.

Alphalactalbumin was investigated in breast cells using the immunoperoxidase technique with a specific anti-alphalactalbumin serum. In 50 benign tumors alphalactalbumin immunoreactivity was demonstrated in the epithelium of fibroadenomas and in fibrocystic disease showing apocrine metaplasia. Alphalactalbumin immunoreactivity, investigated in 124 breast cancers, was present in all cells of lobular tumors but in only 76% of other cancers where the pattern was heterogeneous. Perineoplastic mammary tissue of normal appearance was not labeled with the anti-alphalactalbumin antiserum except where lobular hyperplasia was present. The presence of alphalactalbumin-type immunoreactivity was not correlated with the histopathological staging of Bloom and Richardson, nor with menopausal status. The incidence of positivity was 90% when estrogen and progesterone receptors were present in the tumor. The demonstration of alphalactalbumin using immunoperoxidase could be used to complement the histological classification of breast cancers.

Breast Neoplasms↗

PubMed1984

Relationship between ultrastructure and receptor content of human primary breast cancer.

The ultrastructure of 47 primary breast cancers was studied. For each tumour, the characteristics of approximately 200 malignant cells were examined. Eleven features were scored from 1 to 3 and multivariate analysis showed that seven of these could be used to define an ultrastructural index of differentiation. Differentiation at the ultrastructural level was associated with the presence of steroid receptors. Differentiated tumoral cells contained oestrogen receptor and progesterone receptor in 81.8% and 66.7% of cases, respectively. Poorly differentiated cells contained oestrogen receptors in 50% and progesterone receptor in 14.3% of cases. Comparison of histological grading by the method described by Scarff, Bloom & Richardson with the ultrastructural index of differentiation showed a rather loose correlation which was not significant in this group of 47 patients. The authors conclude that differentiation at tissue or cellular levels yields differing information, only the latter being closely correlated with steroid receptor presence.

Adenocarcinoma↗

PubMed1983

Prognostic index for clinical Stage I cutaneous malignant melanoma.

Thirteen variables were evaluated for their significance in predicting the survival of 148 patients in a retrospective study with clinical Stage I cutaneous malignant melanoma. The variables studied were histological type, tumor thickness, level of invasion, mitotic activity, pigmentation type, existence of ulceration, presence of lymphocytic infiltration, cell type, sex and age of the patient, site of melanoma, and wide local excision preceded or not by contact radiotherapy and associated or not with lymphadenectomy. When these variables were individualized, only seven were significantly related to survival: histological type; tumor thickness; level of invasion; mitotic activity; pigmentation type; existence of ulceration; and sex of the patient. Multivariate analysis based on Breslow's version of the Cox proportional-hazards model was performed on a group of 110 patients. This analysis demonstrated that 5 of the original 13 variables (i.e., mitotic activity, tumor thickness, sex, lymphadenectomy, and site of primary melanoma) could be used to develop a prognostic model. A Gompertz distribution which provided for an appropriate smoothing of the Breslow model estimates was used to derive a simple prognostic index and to predict the survival of individual patients. Fifty-four patients in a prospective study were subsequently evaluated with the Gompertz model in order to test the prognostic accuracy of the model for the five variables.

Adult↗

PubMedDate not supplied

Comparison of Cyfra 21-1 and SCC assays in head and neck tumours.

Patients with head and neck tumours (HNT) have a high risk of early locoregional relapse that is difficult to diagnose. This study evaluated the usefulness of the serum Cyfra 21-1 assay compared to squamous cell carcinoma antigen (SCC) assay for monitoring such patients. Three hundred and twelve HNT patients, including 204 newly diagnosed patients, were followed up for a median of 446 days with serial serum assays for SCC and Cyfra 21-1. Untreated patients showed SCC and Cyfra 21-1 serum levels correlated with each other: concentration was correlated to clinical stage, tumour size (as T1 + T2 vs. T3 + T4) and nodal status. Cyfra 21-1, but not SCC, was related to the presence of metastases and the primary tumour site, with a univariate prognostic value for disease-free survival (p = 0.015). Cox's regression analysis showed that only Cyfra 21-1 was associated with a risk of relapse (p = 0.027). The random coefficient growth curve model applied to serial SCC and Cyfra 21-1 measurements of 111 patients showed that only Cyfra 21-1 exhibited a significant difference between patients with and without relapses. We found Cyfra 21-1 to be more closely related to initial clinical data and disease evolution than SCC, and therefore propose the use of Cyfra 21-1 for monitoring head and neck cancers.

Adenocarcinoma↗

PubMedDate not supplied

Is adjuvant tamoxifen recommended in post-menopausal node-negative breast cancer patients with high estrogen receptor values?

The impact of ER levels on the response to tamoxifen was evaluated in 1,623 postmenopausal primary breast cancer patients treated at our center (median follow-up 8.2 years). In patients receiving adjuvant tamoxifen a significantly longer disease-free survival (DFS) was observed when ER levels were elevated (p<0.00001). Very high ER (>424 fmol/mg protein) appeared to be detrimental in node-negative patients not treated with tamoxifen.

Aged↗