Histological examination of 2859 breast biopsies. Analysis of adequate sampling.
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Biomedical subjects
Publications and source records attributed to F Bonichon.
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Special techniques such as serial macroscopic sectioning (SMS) or immunohistochemical staining (IH) improve the detection rate of micrometastases but this detection is of value only if it improves the prediction of recurrence and survival. We first studied the prognosis of 120 patients with a single micrometastasis detected by SMS in a series of 1,680 primary operable breast carcinoma with a median follow-up of 7 years. A significant difference in recurrence (P = 0.005) and in survival (P = 0.0369) was found between node-negative patients and those with one single SMS micrometastasis, but SMS micrometastases were not a predicting factor by multivariate analyses according to the Cox model. We then studied the prognostic significance of patients with a micrometastasis detected by IH in node-negative carcinoma: 37 micrometastases from a series of 89 invasive lobular carcinoma (ILC) and 13 single micrometastases from a series of 129 invasive ductal carcinoma (IDC). In the ILC group, IH micrometastases had no prognostic value (median follow-up: 9.3 years). In the IDC group, IH micrometastases were correlated with recurrences (P = 0.01) and were the most significant predicting factor, but were less correlated with survival (median follow-up: 15.6 years). Three main points emerge from this study: (1) SMS micrometastases have a prognostic significance and macroscopic sectioning is recommended as a routine technique not requiring excessive work. (2) IH micrometastases in infiltrating lobular carcinoma have no prognostic significance. (3) The value of IH is debatable in infiltrating ductal carcinoma, since the technique is of principal use in predicting recurrences. It should therefore be carefully assessed vs other prognostic factors currently under study.
From 1975 to 1988, 144 patients naive of treatment, with non-metastatic soft tissue sarcoma were treated at Fondation Bergonié by surgery, followed by radiotherapy and without chemotherapy. An analysis of prognostic variables was done on this population to determine patients for whom an adjuvant chemotherapy would be relevant. Prognostic variables in overall survival (OS), metastasis-free survival (MFS), disease-free and local free recurrence survivals were analysed by univariate and multivariate analysis. In multivariate analysis using Cox's model, only tumour depth and tumour grade were significant with the MFS end point, while tumour depth, tumour grade and tumour site were significant when considering OS. A predictive stratification for patients is proposed: a favourable prognostic group with grade 1 tumour or superficial, grade 2 tumour (5-year OS: 97.8%; 5-year MFS: 100%); an intermediate prognostic group with deep, grade 2 tumour or superficial, grade 3 tumour (5-year OS: 58.8%; 5-year MFS: 48.1%); and finally a poor prognostic group with deep, grade 3 tumour (5-year OS: 31.7%; 5-year MFS: 34.1%). Patients in the intermediate and poor prognostic groups who present a high metastatic risk are to be considered for adjuvant chemotherapy trials.
From January 1985 to December 1987, 228 women with breast cancer smaller than 3 cm were treated by surgery +/- radiotherapy. All of them had axillary node involvement (N+) and/or lacked estrogen and progesterone steroid receptors (EPR-). They were randomized in an adjuvant chemotherapy trial comparing 9 intravenous CMF courses (cyclophosphamide, methotrexate, 5FU)--113 patients--to a polychemotherapy consisting of 3 courses of MTV (mitomycin C, thiotepa, vindesine) plus 3 courses of EVM (epirubicin, vincristine, methotrexate)--115 patients. Prognostic factors were well balanced between the two treatment groups. With a 59-month median follow-up, local breast relapses are more frequent in the CMF group, but regional and metastatic recurrences are the same in the two groups. Overall survival is identical. Toxicity is different: alopecia and neurotoxicity are more frequent in the MTV+EVM group, but general and digestive toxicities are equivalent. Haematologic toxicity is greater in the CMF group, requiring more frequent dosage reductions.
Thymidine kinase (TK) was assayed in the cytosol of 210 primary breast cancers to assess its predictive value for response to first line chemotherapy and hormonotherapy. We performed correlations between TK and the other prognosis factors of breast cancer. TK activity is correlated with SBR grading and estrogen receptors. It has a low predictive value for response to chemotherapy and is not useful for hormonotherapy.
The post-surgery zinc depletion reported by Hallböök in 1977 and subsequently confirmed by many authors is now well known. Our study concerns a homogeneous group of 87 female patients undergoing the same surgical procedure: simple or enlarged hysterectomy. Results confirm a mean 35% drop in serum zinc after surgery compared to initial values. The drop is mainly during the operation. A parallel zinc and albumin depletion was noted in 36 patients between the beginning and end of intervention. More systematic zinc supplementation could be proposed before surgery in patients presenting chronic zinc depletion.
From 1963 to 1988, 281 patients with newly diagnosed follicular lymphomas were treated and followed at the Foundation Bergonié. Distribution of stages was: 72 I, 61 II, 83 III and 65 IV. Within stage III, two subgroups were retrospectively defined: stages III1 (32 cases) included patients with less than 8 involved sites, only 1 or 2 above diaphragm, and no spleen or mediastinal enlargement. Stage III2 (51 cases) included the remaining stage III cases. Median follow-up was 9 years. Complete remission (CR) rate was 82%. 10-year overall survival (OS) and time to treatment failure (TTF) rates were, respectively 38% and 29.5%. 10-year time to relapse (TTR) rate was 36%. Statistical analyses showed concordant results with two main prognostic factors: age (less than 60/greater than 60) and stage (I to III1/III2 and IV). Age was the most important factor for OS analysis and stage for CR and TTR analysis. This leads to only three prognostic groups with different outcome. The first includes younger patients (less than 60 years) with limited stages (less than or equal to III1); the second, patients either older than 60 or with advanced stages; the last, elderly patients with advanced stages. CR rates of these three groups were, respectively 97%, 75% and 57%. 10-year OS were, respectively 73.5%, 27% and 0%; 10-year TTR were 54%, 22% and 0%. These results have lead to data which are easy to handle and which can help to establish a rationale for further prospective trials.
In Bordeaux University (France), oncology teaching was individualized in 1972, and an optional oncology course devoted to general practice was created in 1980. To evaluate the adequacy of these two oncology classes for general practitioners and so to adapt our current teaching, we sent to each of 1,219 general practitioners (GP's) of Gironde (county of the southwest of France) an anonymous questionnaire about oncology teaching in prevention, screening and cancer detection, cancer management, and curriculum balance. We received 688 (56.4%) responses. GPs said that as undergraduates, they were insufficiently instructed about screening programs (65%), pain control (80%), palliative care (50%) and fundamental or biological data (greater than 55%). This situation, which showed signs of improvement from 1975 on, has improved even more since 1985. General practitioners, as well as undergraduates, are not yet adequately educated about cancer for general practice, so we have to adapt better our current teaching for undergraduates and those in continuing medical education.
In order to reduce, if not completely suppress, late complications of combined chemotherapy and radiotherapy in Hodgkin's disease (HD), MOPP regimen (mechlorethamine, vincristine, procarbazine and prednisone) was replaced by ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Ninety-four patients with HD clinical stages I to IIIA with no staging laparotomy were treated by three courses of ABVD followed by radiotherapy. Irradiation was performed on extended fields in 41 cases and on involved fields in 53 others. Consolidation chemotherapy was planned in 67 cases with at least one unfavorable prognostic factor, but achieved only in 33 cases. Seventeen patients relapsed within 1 to 46 months after the beginning of treatment. Ten patients died, 7 of HD and 3 of intercurrent diseases or accident. Disease-free survival rate with a median follow-up of 60 months is 80%. This study showed, on the one hand, many digestive and general side-effects after ABVD and, on the other, a satisfactory hematological tolerance. Furthermore, mediastinitis or cardiovascular complications were not more frequent than with MOPP. These results point out the development and use of better tolerated regimens for initial chemotherapy in HD, without jeopardizing the good results of the treatment.
The purpose of this report is to assess whether phenotyping by three monoclonal antibodies routinely used in paraffin sections (Ber-H2-Leu-M1-EMA) and shown to be the most useful for diagnosis may be a predictive factor for recurrences. Among 563 patients diagnosed as having Hodgkin's disease (24% of whom had recurrence), we selected 153 patients with and without recurrence, with matching clinical stage. For all of these cases, histologic material was tested by immunostainings with satisfactory control samples. No phenotype was specific for Hodgkin's disease, although the phenotype Ber-H2-Leu-M1-EMA was predominant. No phenotype was found to be a predictive factor for recurrences, and none was unchanged during the clinical course, except when recurrence occurred as non-Hodgkin's lymphoma.
In June 1982, the Direction of the French Hospitals introduced the project for the medicalisation of the system of information (PMSI) derived from the American Fetter system. The aim of this project was the collection of basic data necessary to the establishment of a national minimum data set base (MDS). Since 1985, a french regional cancer center, the Foundation Bergonié, has collected MDS by computer. Now, we give the results of the analysis concerning 28,379 MDS collected from 1986 to 1988. However, 11,127 (39%) MDS have not yet been analyzed by PMSI as they are connected with external activity or ambulatory care. It is possible to form a diagnosis related group (DRG) from the MDS to analyze the management of hospitals and utilization of means. 279 DRG were formed from 12,252 MDS, in our Institute. In fact, only 30 DRG with a sufficient number of MDS (over 100) were studied. This descriptive study shows that a few DRG maintain homogeneity in terms of length of hospitalisation especially in the surgical sector. It seems necessary to incorporate new criteria for MDS in order to improve the study of DRG; however groups sufficiently large for statistical analysis must be maintained.
From 1972 to 1976, 95 patients with clinical stages I-IIIA Hodgkin's disease were treated by chemotherapy with cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP) before and after extended field radiotherapy. The CVPP schedule gave: (1) a constant drug dosage for each patient independent of body surface or weight; and (2) a total drug dosage dependent on haematological tolerance, since the treatment was given for 21 days or until the leukocyte count dropped to 2 x 10(9) l-1. The drug dosage per unit body surface (or 'dose density') significantly correlates with the drop in leukocyte count (P less than 0.001) and the tumour regression at the end of the induction course (P = 0.020). Disease-free survival is significantly related to dose density (P = 0.050) but not to dose intensity calculated on the duration of treatment (P = 0.240). However, after exclusion of three marginal recurrences due to border-line radiotherapy, the dose intensity significantly correlates with the disease-free survival (P = 0.031) and with the duration of complete remission (r = 0.870).
Tumor grade is currently the most important factor in the staging of patients with soft tissue sarcomas. In previous studies, a histopathologic grading system was described and its reproducibility was tested. The current study reports the value of this grading system in spindle cell sarcomas, which represent about one half of all adult soft tissue sarcomas, the precise identification of which is often difficult. One hundred twenty-five such tumors were studied retrospectively. Malignant fibrous histiocytoma was the most frequent histologic type, followed by leiomyosarcoma, neurosarcoma, and fibrosarcoma. Tumor grade was correlated with the advent of metastases and survival, and was the main prognostic factor according to multifactorial analysis introducing clinical prognostic factors.
The purpose of a randomized trial achieved in a single centre (Fondation Bergonié, Bordeaux, France) was to compare chemotherapy alone (intravenous CMF) versus chemotherapy and hormonotherapy (CMF plus tamoxifen-30 mg per day during 2 years), for patients with stage II breast carcinoma and positive values of estrogen and/or progesterone receptor (EPR) (greater than 10 and greater than 15 fmoles mg protein-1 respectively). Three hundred and thirty four women treated by surgery +/- radiotherapy are included in this trial from 06.01.81 to 12.31.84. No patient is lost for follow-up. Eight are excluded. Three hundred and twenty six patients are evaluable with a 38 month median follow-up. For EPR assay, the dextran charcoal micromethod was used in the same centre. The two groups are identical as far as age, hormonal status, TNM, EPR values, and histological features are concerned. Analysis of results shows a significant improvement of relapse free survival (p = 0.018) and also overall survival (p = 0.04) for the CMF+ tamoxifen group.
From 1966 to 1985, 103 patients with a localized (stages I and II) follicular lymphoma (Kiel classification) were treated at the Fondation Bergonié. Clinical staging was performed using, after physical examination, chest X-rays (100%), bipedal lymphangiography (98%) and unilateral bone marrow biopsy (BMB) (51.5%). The patients were then treated by radiotherapy with or without chemotherapy. Overall survival (OS) at 5 and 10 years is 69 and 56.3%, respectively. Relapse-free survival (RFS) is 53.7 and 49%. Unifactorial analysis shows three prognostic parameters to be independently significant in terms of OS: age, stage and B symptoms. In terms of RFS, only 2 factors are significant: age and B symptoms. Multivariate analysis (Cox model) shows that age is a more important prognostic factor than stage.
From 1972 to 1976, 102 patients with stages I-IIIA Hodgkin's disease (HD) were treated by chemotherapy with cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP: two courses) associated with extended field radiotherapy. Staging included neither laparotomy nor splenectomy (clinical staging). Treatment included neither splenic irradiation nor maintenance therapy. Complete remission was achieved for 98 patients and 11 of them recurred up to 94 months after treatment. Median follow-up of this controlled study is 13 years. Disease free survival (DFS) is 87% at 6 years and 84% at 10 and 15 years. Overall survival is 77% at 10 and 74% at 15 years. Disease specific survival is better (91% at 10 and 87% at 15 years) since only 38% (10/26) deaths were due to HD. The other deaths (16/26) with no evidence of HD were due to second cancer and intercurrent disease. Prognostic analysis of DFS by log-rank test gives significance to the following factors: contiguous extra-nodal involvement (P = 0.008), more than 3 involved sites (P = 0.01), signs of compression (P = 0.02), clinical stage IIIA (P = 0.03), infradiaphragmatic stages I-II (P = 0.04). The potential risk of secondary cancer is difficult to assess.
Eighty patients with prostatic cancer have been treated with an LH-RH analogue (Zoladex). Ten had no metastasis, and hormone therapy was used as an induction treatment before curative radiotherapy. The others had metastatic disease and, in some cases, had already received some form of endocrine therapy. Patients received a monthly injection of Zoladex (3.6 mg). No progressive disease was noted among patients with nonmetastatic tumors; of the patients with metastases, those who were previously untreated had a higher response rate (14.8% complete response) and longer progression-free and overall survival. Toxicity was mild in spite of two cases of disease flare.
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