Minimal breast cancer: a clinically meaningful term?
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Biomedical subjects
Publications and source records attributed to G Contesso.
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The dosage of estrogenic receptors (ER) was performed on 80 cytosols of human breast carcinomas "immediately operable", by using a methode consisting of a single saturating dose (5 nM) with carbon-dextran and a new immuno-enzymatic method commercialized by ABBOTT laboratories using anti-ER monoclonal antibodies. The concordance is excellent between the two methods in terms of positivity. The results are significantly higher with the ER-IEA method than with the biochemical method (p. less than 1.10(-5]. The regression of the ER-IEA method as compared to the biochemical method is linear with a regression line: Y (ER-IEA) = 0.82 X (ER-Biochem) + 0.76 (logo10 conc. fmoles/g tissue). The correlation is good between the two methods (r = 0.90). A significant relationship (p less than 0.01) has also been observed with the histological grade of the carcinoma. Finally, the immuno-enzymatic technique seems particularly well adapted to small biopsies and slightly positive tumors.
1,271 patients with breast cancer treated at the Institut Gustave Roussy between 1967 and 1972 and with a minimum follow-up of 10 years, have been studied in order to analyse the risk factors for bilateralization. Patients with metastases at presentation (160) who have an incidence of bilateralization at two years of 20% have been excluded since the contralateral tumor is regarded as part of the metastatic process. For 1,111 patients, non-metastatic at presentation, the following factors have been studied: age, T-stage, N-stage, tumor grade, tumor growth rate (doubling tumor size in less than six months) and the presence of inflammatory signs. Of these factors, only advanced T stage, fixed axillary lymphadenopathy and the presence of inflammatory sign were associated with a significantly increased risk of bilateralization. For patients presenting with T1 tumors the incidence of bilateralization is 19% at 10 years but this is probably because relatively more of these patients lived long enough to develop a second cancer. A more detailed histopathological study was performed on 682 patients whose tumors were operable at presentation and for whom the following histological characteristics are known: type, grading (Scarff and Bloom), number of axillary nodes involved by tumor and anatomical size of the tumor. None of these characteristics was found to increase the risk of bilateralization. Comparing the two breast tumors (and excluding those with a diffuse infiltration in either breast) in 74 patients in whom the exact tumor site was known, in only 7, was the second tumor a "mirror-image" of the first. Overall, MO patients with bilateral tumors have a decreased survival compared with those with unilateral tumors. For those patients operable at presentation, the 10 year survival is 51% and 63%. The conclusions of this study are that there are two populations of patients with bilateral breast cancer: Those in whom the controlateral tumor is part of a generalized metastatic process and occurs particularly in those with a poor prognosis (metastases at presentation, inflammatory carcinomas, fixed lymphadenopathy). Those in whom there is a relatively long interval (5-10 years) between the development of the two tumors who have not any metastases. This population particularly comprises patients with T1 tumors thus for whom continuing clinical and mammographic follow-up is justified.
The possibly prognostic value of elastosis in breast carcinoma has usually been visually evaluated, using subjective gradings whose variability has led to contradictory conclusions. We used a Magiscan 2 automated image analyzer to perform objective measurements on elastosis on a set of 52 slides that were also subjectively evaluated. The wide range of parameters measurable by the automated system seemed likely to successfully deal with the lack of homogeneity of elastosis that causes problems in subjective evaluations. The homogeneity parameters (percentage distributions of elastosis in each slide) were processed by factorial analysis. On the plane defined by the first two factors, the principal components analysis produced a clustering of cases that was, on the whole, in concordance with the subjective evaluation.
Forty-eight, computed tomography (CT) examinations undertaken in 30 patients with osteosarcoma of long bones were studied in detail, their diagnostic information being compared with that obtained from corresponding plain films. The latter were of more value in assessing peripheral bony involvement, by cortical extension and periosteal reaction, while the former, in general, permitted more accurate observation of extensions into adjacent soft tissues. Recognition of such extensions, however, was vitiated when they arose in relation to the proximal ends of the tibia, fibula, and humerus and when a haematoma had developed as a result of a biopsy. Plain films were also of more value in appreciation of response to chemotherapy. On the other hand CT is the only examination which permits a satisfactory study of intramedullary extensions of the tumour and in consequence is invaluable in determining the exact sites required for local resection. No cases of skip metastases were observed in our series, although similar appearances due to nutrient vessels or bony ridges, remote from the primary tumour, were noted on several occasions. Differentiation of these densities proved to be easy, particularly in the case of nutrient vessels when examination of the contralateral bone showed them to be symmetrical. Several authors have described the role of CT in the evaluation of local extensions. This paper reports the difficulties and errors encountered by us.
Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.
This is a clinicopathologic study of 6 cases of alveolar soft-part sarcoma. The patients age ranges from 8 to 47 years. All patients are women. In 5 cases the localization of the primary tumor is the lower extremities. Histologically the tumors have a distinctive organoid pattern outlined by thin-walled capillaries and are composed of nests of large polyhedral cells with abundant finely granular, acidophilic cytoplasm. Two tumors, among the 4 tested cases, have cytoplasmic PAS positive diastase-resistant crystalline structures. Electron microscopic study of one tumor shows intracytoplasmic glycogen, small membrane-bound electron-dense granules, Golgi lamellae and crystalline structures. Immunoperoxidase study performed in one case reveals a positivity with antikeratin and anti-enolase (NSE) antibodies. The prognosis of this tumor is poor. The main metastasis are in the lung and in the brain. Often the patients develop metastasis before detection of the primary tumor. The histogenesis of alveolar soft part sarcoma and the identity of the characteristic crystalloids remain open for discussion.
"Le Centre de Prolifération d'Aschoff" (CPA) has many synonyms: radial scar, benign sclerosing ductal proliferation, non encapsulated sclerosing lesions, fibroelastic center, fibroadenosis with fibroelastic core etc... In a retrospective study from the files of the Gustave-Roussy Institute, 88 cases were found: 18 cases between 1955 and 1959 and 70 cases more recently, between 1976 and 1981. CPA is an unusual lesion, observed in 2% of benign breast lesions, and in less of 1% of malignant breast lesions. Macroscopically, when CPA is not associated to a carcinoma, it has either a pseudotumoral feature (46% of the cases), or only a microscopic appearance (54% of the cases). In these last cases, it is always found by chance at the time of the examination of specimens of fibrocystic disease. When it is associated to a carcinoma, these two features are less well individualized. Mammographically and macroscopically, they are often problematical. They cause considerable diagnostic problems because of their pseudotumoral features, being similar to small stellate carcinomas. Two cases were misinterpreted at the time of the extemporaneous examination for a carcinoma and in 36 other cases, the diagnosis was uncertain and the definitive report was delayed. For the non-pseudotumoral form, a relationship was found in this series between previous cytological aspirations and CPA. The evolution of this lesion was difficult to evaluate because of the great number of the patients lost to follow up in this series. Although a slight trend was observed for patients to subsequently develop a breast carcinoma, no statistically significant difference was observed. From this study, close follow-up of these patients is considered necessary.
Breast sarcoma are rare, representing 1% of all malignant breast tumours. This is a retrospective study of 25 patients with a breast sarcoma, treated at Institut Gustave Roussy from 1954 to 1981. Thirty six per cent of these arose in a cystosarcoma phyllodes. A variety of histologies were found, the main one being malignant fibrohistiocytoma (44%). Nodal involvement was rare (4%) and, as in other sarcoma, hematogenous spread of metastases was more usual. Local recurrence occurred in 44% of cases and distant metastases (usually pulmonary) in 24%. The 3 year disease-free survival was 60% and the major prognostic factor was the mitotic index. Surgery is the treatment of choice of these tumours, supplemented by local irradiation in those cases where only a tumorectomy has been performed. The role of adjuvant chemotherapy remains undefined.
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A prospective study of the prognostic significance of the labelling index (LI) was undertaken in 1972. The LI of the primary tumor was measured consecutively on 128 patients with mammary carcinoma at the time of initial treatment, following in vitro incubation of specimens with tritiated thymidine. The follow-up for all patients has now extended over 10 years. Relapse-free survival and total survival are significantly higher in patients with a low LI. A multivariate analysis of the prognostic factors, carried out with Cox's model, showed that LI is the most predictive indicator with respect to survival. The size of the tumor is the second most predictive indicator, while histological grading and the number of involved lymph nodes are less predictive. These results strongly suggest that proliferative activity as assessed by LI is directly related to metastatic dissemination probability, independent of other prognostic factors.
A clinical trial was conducted at the Institut Gustave Roussy between October 1972 and December 1980 to compare mastectomy with local excision plus Cobalt-irradiation, in patients with breast cancer tumors of 20 mm in diameter or less at macroscopic examination. Low-axillary dissection and extemporaneous histologic examination were carried out for all patients. If one or more positive nodes were found, complete axillary dissection was performed. The study included 179 patients. No significant difference was detected in either overall or relapse-free survival between the two groups, although the conservatively treated group showed slightly better results. The results of conservative treatment were esthetically satisfactory in 92% of the cases. The trial included a second randomization for the patients with positive axillary nodes to assess the value of nodal area irradiation; 72 patients were studied in this part of the trial. No significant differences were found between the two groups after adjustment for the number of positive axillary nodes, although the no-nodal irradiation group showed better results and less complications than the nodal irradiation group.
The results of a randomised trial of polyadenylic-polyuridylic acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow up period of 87 months. Of the 300 patients included in the original trial, 145 had been allocated to conventional treatment alone and served as controls. At the time of review the overall survival of the group given polyadenylic-polyuridylic acid was significantly improved (p less than 0.05) as compared with that of the controls given conventional treatment alone. Significant benefit (p less than 0.02) was also observed among patients with evidence of disease in lymph nodes, the best results occurring in those with up to three invaded nodes, who showed a significant increase in both overall and relapse free survival. No evidence of toxicity was recorded. These findings confirm the value of polyadenylic-polyuridylic acid as adjuvant treatment for operable breast cancer. Results in an experimental model and in patients receiving the adjuvant suggested a possible role of interferon and natural killer (NK) cells in the mechanism of action.
The pathological features of 155 adult patients with soft-tissue sarcomas were studied retrospectively, in an attempt to set up a grading system for these tumors. As the first step, seven histological criteria (tumor differentiation, cellularity, importance of nuclear atypia, presence of malignant giant cells, mitosis count, pattern of tumor necrosis and presence of vascular emboli) were evaluated in a monofactorial analysis. Five of these (tumor differentiation, cellularity, mitosis count, tumor necrosis, and vascular emboli) were correlated with the advent of metastases and with survival. A multivariate analysis, using a Cox model, selected a minimal set of three factors (tumor differentiation, mitosis count, and tumor necrosis) the combination of which was necessary and sufficient to retain all the prognostic information. A grading system was elaborated, which turned out to be correlated with the advent of metastasis and with patients' survival. A second multivariate analysis introducing clinical prognostic features showed that the histological grade was the most important prognostic factor for soft-tissue sarcomas. Thus, this grading system appears to be highly interesting because of its prognostic value and the facility of its elaboration. However, its reproducibility should be tested.
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The relationship between the size of the primary tumour upon initial treatment and the incidence of distant metastasis during the course of the disease was investigated using data from 2648 breast cancers treated at the Institut Gustave Roussy between 1954 and 1972. This analysis suggests the existence for each tumour of a critical volume (threshold) at which the first remote metastasis is initiated. The correlation between the size of the primary tumour and the probability of metastatic dissemination was assessed as well as the influence on this correlation of two prognostic indicators: histological grade and number of involved lymph nodes. It was found that the threshold volume is strongly correlated with the number of involved lymph nodes and the histological grading.
We looked systematically for the presence of receptor like binding sites for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) in the cytosol from 22 breast cancers. Cytosols were centrifuged on 5-20% sucrose gradients after labeling with tritiated 1,25 (OH)2D3 (3H-1,25(OH)2D3 or 25-hydroxyvitamin D3 (25(OH)D3 alone or in the presence of a large excess of these unlabeled sterols. Binding sites for 1,25 (OH)2D3 migrating in the 3.5-3.7 S region were found in 7 out of 22 cancers, while 5.5-6.5 binding sites for 25 (OH)D3 were found in all cytosols. In a patient in whom cytosol containing a 3.5-3.7 S binding site was in sufficient amount, quantification of 1,25 (OH)2D3 binding indicated a KD of 0.28 nM and a maximal binding capacity of 0.15 pmol/mg prot. No relation was found between the presence or the absence of 1,25 (OH)2D3 binding sites and the histological type, the extension of the cancer, the presence of radiological or histological calcifications, the amount of estrogen or progesterone receptors, the plasma calcium or phosphate concentration and the emergence of metastases after 1 year. The significance of the presence of receptor-like binding sites for 1,25-(OH)2D3 in one third of breast cancers remains therefore unknown at the present time.