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K Hacene

Publications and source records attributed to K Hacene.

At least 19 recordsLinked to original sources
PubMed2006

CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study.

BACKGROUND: CA 125 assays enable treatment-response monitoring in ovarian cancer. PATIENTS AND METHODS: A multicentric study of CA 125 kinetics under induction chemotherapy was performed in 631 patients. CA 125 half-life was calculated by mono-compartmental logarithmic regression. Nadir CA 125 concentration and time to nadir were also studied. Survival analyses for disease-free survival (DFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox) models. RESULTS: For 553 stage IIC-IV patients, 459 (83.0%) relapsed and 444 (80.3%) died from cancer. Median (range) follow up time was 32 months (2-214 months). Median (range) for CA 125 kinetics were: 263 kU/l (5-52000 kU/l) before 1st course, 15.8 days (4.5-417.9 days) for CA 125 half-life, 16 kU/l (3-2610 kU/l) for nadir and 85 days (0-361 days) for time to nadir. Pre-chemotherapy CA 125, its half-life, nadir concentration and time to nadir all had a univariate prognostic value for DFS and OS (P<0.0001). In Cox models, CA 125 half-life, residual tumour (P<0.0001 for both), nadir concentration (P=0.0002) and stage (P=0.0118) were the most powerful prognostic factors for DFS. For OS, the significant variables were similar, with age ranking last (P=0.0319). CONCLUSION: Among well-established prognostic factors in ovarian cancers, CA 125 half-life and nadir concentration bear a strong and independent prognostic value.

Adult↗
PubMed2005

Management and clinical outcomes of pregnant patients with invasive cervical cancer.

BACKGROUND: The objective of this study was to evaluate the clinical outcomes and to discuss the management of women presenting with an invasive cervical cancer during pregnancy. PATIENTS AND METHODS: We retrospectively reviewed patients treated for an invasive cervical cancer diagnosed during pregnancy between 1985 and 2000 in our institution. RESULTS: Twenty-one pregnant patients among a total of 487 women were treated. Thirteen, five, two and one, respectively, were diagnosed during the first, second and third pregnancy trimester and post-partum. The FIGO stage was IB in 15 cases, IIB in five cases and IVA in one case. Mean follow-up was 64 months (range 2-165). Overall and disease-free survival at 5 years were 82% and 79%, respectively. All five patients diagnosed in the second trimester were alive. Two of the 13 patients and one of the two patients diagnosed during the first trimester and the third trimester, respectively, died of their disease. No difference was observed between the nine patients whose treatment was delayed or not. CONCLUSIONS: Invasive cervical cancer during pregnancy is rare but is a dilemma for women and their physicians. The present study and review of the literature suggest that pregnancy does not seem to influence the prognosis of cervical cancer. Delayed treatment could be proposed to selected patients diagnosed at the end of the second trimester or at the beginning of the third trimester, with a small tumor (<2 cm) and negative nodes, after a multidisciplinary approach.

Adult↗
PubMed2001

ERBB2 status and benefit from adjuvant tamoxifen in ERalpha-positive postmenopausal breast carcinoma.

We examined the relation between ERBB2 gene expression (as determined by a real-time quantitative RT-PCR assay) and the response to adjuvant tamoxifen therapy in a well-defined cohort of 125 ERalpha-positive postmenopausal patients with breast cancer. Although ERBB2 overexpression was associated with shorter relapse-free survival in univariate analysis (P=0.00029), ERBB2 did not persist as an independent prognostic factor in multivariate analysis. Nevertheless, when we analyzed the ERBB2 mRNA level as a continuous variable, the higher the ERBB2RNA level, the poorer the outcome (P=0.00036). The results point to the need for a quantitative ERBB2 expression assay for use in future studies of ERBB2-based clinical management of breast cancer.

Aged↗
PubMed2000

[Sem: a suitable statistical software adaptated for research in oncology].

Many softwares have been adapted for medical use; they rarely enable conveniently both data management and statistics. A recent cooperative work ended up in a new software, Sem (Statistics Epidemiology Medicine), which allows data management of trials and, as well, statistical treatments on them. Very convenient, it can be used by non professional in statistics (biologists, doctors, researchers, data managers), since usually (excepted with multivariate models), the software performs by itself the most adequate test, after what complementary tests can be requested if needed. Sem data base manager (DBM) is not compatible with usual DBM: this constitutes a first protection against loss of privacy. Other shields (passwords, cryptage...) strengthen data security, all the more necessary today since Sem can be run on computers nets. Data organization enables multiplicity: forms can be duplicated by patient. Dates are treated in a special but transparent manner (sorting, date and delay calculations...). Sem communicates with common desktop softwares, often with a simple copy/paste. So, statistics can be easily performed on data stored in external calculation sheets, and slides by pasting graphs with a single mouse click (survival curves...). Already used over fifty places in different hospitals for daily work, this product, combining data management and statistics, appears to be a convenient and innovative solution.

Clinical Trials as Topic↗
PubMed1997

Comparison of a new microplate oestrogen receptor (ER) enzyme immunoassay with other ER detection methods.

In a study involving 50 breast cancer tumours, we compared two oestrogen receptor (ER) detection methods developed by us--a microplate immunoenzymometric assay (EIA96) and an immunohistochemistry kit (HistoCIS-ER)--with the radioligand assay (RLA), the Abbott immunoenzymometric assay ER-EIA and the reverse transcriptase polymerase chain reaction technique (RT-PCR). Among the three ER protein cytosolic assays (EIA96, ER-EIA and RLA), the two EIAs showed the best agreement (y = 1.086x - 7.840; r2 = 0.876). At the calculated optimal cut-off values (8 and 14 fmol mg(-1) protein for EIA96 and RLA respectively), EIA96 was more sensitive than RLA (0.94 for EIA96, 0.88 for RLA), but slightly less specific (0.82 for EIA96, 0.94 for RLA). The Cox logistical regression model applied to EIA96, RLA and RT-PCR showed that EIA96 discriminated the best between ER-EIA+ and ER-EIA- samples. The RT-PCR technique and HistoCIS-ER both had a positivity-negativity concordance of 86% with EIA96.

Adenocarcinoma↗
PubMed1996

Prognostic factors for patients with localized primary malignant fibrous histiocytoma: a multicenter study of 216 patients with multivariate analysis.

BACKGROUND: The purpose of this study was to determine the independent prognostic variables in a well documented subset of 216 patients with localized primary malignant fibrous histiocytomas (MFH). METHODS: Between the years 1980 and 1989, 216 patients with localized, primary (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC] Stage I-IVA) MFH were evaluated and treated in 10 participating centers of the sarcoma group of the French Federation of Cancer Centers (FNCLCC). Clinicopathologic factors were collected retrospectively and entered into a cooperative database. Tissue slides of all cases were jointly reviewed microscopically by the pathology subcommittee. Surgical treatment was performed on all but 6 (3%) patients. One hundred ninety-five patients (90%) were free of gross disease, with complete local control at the end of the initial treatment. The adjuvant treatment was radiotherapy in 78 patients (36%), chemotherapy in 19 patients (9%), and both in 61 patients (28%). RESULTS: The median follow-up was 3.5 years (range, 45 days to 12 years). Five-year actuarial rates of disease specific (DSS), metastasis free (MFS), and local recurrence free (LRFS) survival were 70%, 63.3%, and 62.7%, respectively. Multivariate analyses showed that the adverse prognostic factors independently associated with decreased disease specific survival were UICC/AJC Stage III + IVA (P < 0.00001; relative risk [RR], 3.27; 95% confidence interval [CI], 1.6-6.58), residual macroscopic disease following primary local therapy (P = 0.00024; RR, 3.99, CI, 2.04-7.82), deep tumor location (P = 0.0045; RR, 3.37; CI, 1.21-9.38), non-myxoid histology (P = 0.0056; RR, 9.28; CI, 1.03-83.41), and age older than 50 years (P = 0.037; RR, 2.19; CI, 1.04-4.61). Two factors were significantly related to MFS in the patients with the poorest prognosis: histopathologic Grade 3 (P < 0.0001, RR, 3.46; CI, 2.02-5.91) and tumor size greater than 8 cm in largest dimension (P = 0.0012; RR, 2.78; CI, 1.36-3.66). With regard to LRFS, patients who did not undergo radiotherapy had reduced local control (P = 0.0043; RR, 2.36; CI, 1.46-3.83). CONCLUSIONS: Resection of all macroscopic disease was independently associated with improved disease specific survival and adjuvant radiotherapy significantly decreased the local relapse risk. Histopathologic grade was the most important prognostic factor for DSS and MFS.

Actuarial Analysis↗
PubMed1994

Anti-colony-stimulating factor-1 antibody staining in primary breast adenocarcinomas correlates with marked inflammatory cell infiltrates and prognosis.

BACKGROUND: Clinical studies have shown that a marked lymphoplasmocytic reaction in breast tumors is associated with poor prognosis. Such findings raise the possibility that an inflammatory cell reaction might be a tumor-induced response that tends to promote tumor growth. PURPOSE: We assessed the expression of colony-stimulating factor-1 (CSF-1) as well as the prevalence of specific tumor-infiltrating lymphocytes and monocytes in breast tumors. METHODS: Tissue sections were obtained from archival paraffin blocks from 196 breast cancer patients. Seventy-eight percent of the women had been treated by mastectomy and 22% by lumpectomy. Median age of the patients was 54 years, and median follow-up was 7.3 years. Immunohistochemical and in situ hybridization techniques were used to characterize the specimens. RESULTS: Markedly high numbers of CD45RO-positive T- and L26-positive B-cell infiltrates were found in 13% and 17% of the tissue specimens, respectively. CSF-1 receptor-positive monocytes were detected in 48% and CD68-positive monocytes in 90% of the tumors. In turn, tumors with large fractions of CD68-positive monocytes also showed CSF-1 receptor-positive monocytes (P < .0001). CSF-1 was expressed significantly in 74% of the tumors and the CSF-1 receptor in more than 50% of the tumors. Tumors with high percentages of CSF-1 expressing cells also had marked monocyte infiltrates (P = .035). The presence of marked CD45RO-positive T-cell infiltrates and apparent nuclear staining of CSF-1 in tumor cells were associated with the more frequent occurrence of metastases (P = .02 and P = .04, respectively) and with poor survival (P = .02 and P = .03, respectively). CONCLUSIONS: Large numbers of CD45RO-positive (activated memory but noncytotoxic) T cells as well as a predominant nuclear staining pattern for CSF-1 are associated with a poor outcome in breast cancer patients. IMPLICATIONS: Nuclear retention of CSF-1 could reflect CSF-1 turnover and function in tumor cells, but new approaches are needed to establish the significance of these observations. Secreted CSF-1 appears to cause monocyte recruitment and activation, thereby modulating immune functions and potentially the expression of the CD45RO phenotype in T cells.

Adenocarcinoma↗
PubMed1994

[Difficulties encountered in the evaluation of prognostic criteria of breast cancer: apropos of the experience of the René Huguenin center].

The use of prognostic factors to help select breast cancer patients for adjuvant therapy is of considerable concern to the oncology community. This need for selection of prognostically less favorable cases is stimulating investigators to identify new and more powerful prognostic factors. Unfortunately however, this identification process is becoming more confusing because of a lack of guidelines for investigators to use to study new factors and for reviewers and readers to use to evaluate papers on this topic. In this paper, we will describe across our experience the main problems encountered in the study of biological prognostic studies. Considering evaluation criteria to be developed in the future, it appears that only multicentric and multidisciplinary structures are able to define decisional trees based on technically and clinically validated parameters in particular patients subgroups. Such a structure exists at the european level ("Receptor Study Group" of the EORTC) and a similar structure has now been created in France to answer these questions.

Breast Neoplasms↗
PubMed1993

Sequential identification of factors predicting distant relapse in breast cancer patients treated by conservative surgery.

BACKGROUND AND METHODS: Predictors of distant relapse following conservative surgery for breast cancer were studied in a review of 425 women. Five steps of breast cancer patient management were defined in which increasing amounts of information, potentially relevant to prognosis for metastasis-free survival (MFS), were available: (1) clinical, (2) biopsy, (3) tumorectomy, (4) axillary dissection, and (5) adjuvant treatment. At each step, a prognosis study based on the Cox model was carried out using all acquired information from the first step. RESULTS: Among the 21 studied variables, 5 were independent stable risk factors in predicting MFS: (1) clinical node status, (2) modified Scarff-Bloom-Richardson (MSBR) histoprognostic grade, (3) progesterone receptor (PR), (4) anatomic tumor size, and (5) histologic lymph node status. These factors were progressively identified throughout the successive prognostic analyses and kept their significance at the reference step (axillary dissection step where all information is acquired). According to the prognostic score based on the significant variables, a stratification of the patients had been built at each step, identifying three risk groups (low, moderate, high). Even at biopsy step, the mere knowledge of clinical information, such as clinical node status, and biopsy information, such as MSBR grade and PR status, would enable 68% of the patient to be well classified according to the stratification of reference. Knowledge of an additional factor, such as anatomic tumor size, would bring the rate up to 88%. Some subsets of patients with stable prognosis throughout the steps were identified and their profiles were described. It is noticeable that 95% of the patients, classified low risk at the biopsy step, were patients that were stable. CONCLUSIONS: The early recognition of patients, highly curable by local therapy alone, would obviate aleatoric neoadjuvant treatment.

Adult↗
PubMed1993

Immunoradiometric assay of pro-cathepsin D in breast cancer cytosol: relative prognostic value versus total cathepsin D.

In breast cancer cell lines, the maturation of pro-cathepsin D into enzymatically active cathepsin D is altered, leading to its increased secretion. In order to specifically assay pro-cathepsin D (52 kD form) in breast cancer cytosol, we monitored a solid phase sandwich radioimmunoassay using D9H8 and D7E3 monoclonal antibodies raised against human pro-cathepsin D from MCF7 cells. Pro-cathepsin D was assayed in 108 primary breast cancer cytosols in which total cathepsin D was previously found to be correlated with metastasis. Pro-cathepsin D concentrations were found to be correlated with total cathepsin D and with lymph node invasion, and was slightly higher in premenopausal patients. By contrast, Cox multiparametric analysis showed that pro-cathepsin D status had no prognostic value for survival, or metastasis free survival contrary to total cathepsin D status. This first study shows the technical validity of the pro-cathepsin D assay but indicates that it has less value as a prognostic marker than total cathepsin D. This study also shows that the proportion of pro-cathepsin D recovered in vivo (1-6%) is much less than that produced in cell lines and suggests that the secreted pro-enzyme might be activated in the tumour extracellularly or following its reinternalisation.

Biomarkers, Tumor↗
PubMed1993

Immunohistochemistry of pS2 in normal human breast and in various histological forms of breast tumours.

Expression of pS2 was studied by immunocytochemistry in normal breast tissue (n = 20), benign tumours (n = 9) and 145 breast cancers representative of the different histological types. pS2 immunostaining was scored as negative (D1 = 0-5% stained cells), positive (D2 = 5-75% stained cells) or highly positive (D3 > 75% stained cells). pS2 protein was evident in all normal breast samples examined. Six of nine benign lesions showed pS2 staining. In both cases, immunostaining was weaker than in breast cancers. Of breast cancers, 77/145 (53.1%) were pS2 positive, including 33.1% with intense staining. The presence of pS2 was not correlated with the age of patients, the size of the primary tumour, or lymph node status, but was correlated with histological grading and nuclear grading. pS2 expression was also correlated with menopausal status and oestrogen receptor status (59% of receptor-positive tumours were pS2 positive), but not to progesterone receptor status. pS2 expression in breast carcinomas is not a characteristic of specific histological types. Although this protein is predominantly expressed in oestrogen receptor-positive and differentiated tumours, it shows oestrogen-independent expression in about 30% of cases.

Aged↗
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↗
PubMed1992

Association between restriction fragment length polymorphism of the L-myc gene and lung metastasis in human breast cancer.

EcoRI restriction fragment length polymorphism (RFLP) of the L-myc gene was examined in leukocyte DNAs isolated from 381 breast cancer patients. No differences in the patterns of L-myc RFLP were found between breast cancer patients and healthy individuals. However, among 97 patients who relapsed, a statistical correlation was found between L-myc RFLP and lung metastases (p less than 0.05). These results are in close agreement with previous findings in patients with cancer of the lung, bone or kidney, and suggest that L-myc RFLP may be a useful marker for predicting lung metastasis in some human cancers.

Breast Neoplasms↗
PubMed1992

Prognostic significance of tumor phosphatidylcholine stearic acid level in breast carcinoma.

The involvement of lipid enzymes in the action of oncogenes at the cell membrane level has suggested that membrane lipids could play a role in modulating the growth of tumors. We previously found that breast cancer patients with a low level of polyunsaturated fatty acids in their primary tumor's phosphatidylethanolamine had a high risk of early occurrence of visceral metastasis. In the present study, we prospectively examined whether fatty acid composition of tumor membrane phosphatidylcholine had a prognostic significance in a series of 63 patients with a localized presentation of breast cancer. Membrane phospholipids were extracted from the carcinoma tissue obtained at the time of surgery, phosphatidylcholine was purified, and its fatty acids were analyzed by capillary gas chromatography. During the follow-up period, 20 patients developed metastasis. In these patients, the proportion of stearic acid containing phosphatidylcholine was significantly lower than it was in the tumors of the 43 patients who remained metastasis-free. Multivariate analysis according to Cox showed that low stearic acid level in tumor phosphatidylcholine and high mitotic index were independently predictive of subsequent metastasis. The predictive value of stearic acid level on metastasis risk was higher in node-positive patients than in node-negative patients, allowing individualization of a subgroup of low stearic acid level, node-positive patients with very poor prognosis. We concluded that stearic acid level in tumor membrane phosphatidylcholine is an independent intra-tumor marker of breast cancer prognosis. This finding is new evidence that tumor's structural lipids are linked to the growth of breast cancer.

Adult↗
PubMed1992

Prognostic value of progesterone receptor after long-term follow-up in primary breast cancer.

In a previous study of a series of 105 patients with primary breast cancer we found that the progesterone receptor (PgR) status was an important prognostic factor for early recurrences. 95 patients from the same series were followed-up for a median of 9.5 years and reassessed for the prognostic value of PgR status by univariate and multivariate statistical methods. In univariate analysis, the disease-free interval was only related to the lymph-node status. For overall survival, PgR and combined PgR-ER (oestradiol receptor) status had a prognostic value (P = 0.035 and 0.05, respectively). Moreover, PgR status was found to be discriminant for the survival of the node-negative patients (P = 0.017). In multivariate analysis, ER and PgR status were not significant, indicating that receptor status is not a powerful predictor of the course of breast cancer.

Adult↗
PubMed1991

[Reevaluation of indications for adjuvant hormone therapy in primary breast cancer with high metastatic risk].

This study concerns the correlation between ER and PR status, menopausal status and the effect of adjuvant hormonotherapy in high risk primary breast cancer patients. We have compared the results obtained in a randomized trial (Institut Paoli-Calmettes, Marseille) with those of a historic series (Centre René Huguenin, Saint-Cloud). The patients presented the same clinical and histological criteria and received identical therapeutic protocols (chemotherapy and/or hormonotherapy). Compared with patients receiving no adjuvant treatment, it appeared that: 1) in post-menopausal patients, a significant detrimental effect of tamoxifen was found in ER-negative patients, while in ER-positive patients hormonal treatment was well correlated with both the presence and level of steroid receptors; 2) in pre-menopausal patients, hormonal therapy (oophorectomy + tamoxifen) appeared to be mediated by a complex mechanism involving more than an ER-positive cell population. In the light of the published results, the present findings underline the importance of reevaluating the indications of hormonotherapy in terms of hormone receptors and menopausal status. They also indicate the importance of biological factors in the evaluation of response to therapy. They can identify, subsets of patients in whom a given therapeutic protocol is detrimental, even though it may be beneficial for the overall population. heterogeneity in response to therapy among patient subsets is one of the most important problems which confronts medical statisticians and clinical investigators.

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↗