Search

A rabbit-specific polyclonal antibody was obtained raised to a synthetic peptide corresponding to the 1238-1255 C-terminal predicted sequence of the c-erbB-2 protein. This antibody was used in an immunohistochemical procedure to detect the c-erbB-2 protein on a series of 88 paraffin-embedded human breast carcinomas. In 14/88 cases (16%) the c-erbB-2 protein was found to be overexpressed (immunohistochemical score > 1) with a good concordance with the previously determined mRNA level (79/88 cases: 90%). Prognostic significance of c-erbB-2 protein overexpression as detected by immunohistochemistry was tested by the log-rank test. The relative risk of relapse is higher for patients with an immunohistochemical score > 1 (p = 0.00002). In a multivariate analysis of the c-erbB-2 immunohistochemical score was the only powerful parameter (p < 1 x 10(-3). In conclusion, this antibody seems to be a valuable tool in estimating the c-erbB-2 protein regarded in our series as a parameter able to identify a subgroup of operable breast cancer patients with a high risk of relapse.

In order to determine the prognostic value of c-erbB-2 protein and Epidermal Growth Factor Receptor (EGF-R), we used an immunohistochemical procedure with specific antibodies on paraffin-embedded material from a series of 73 operable breast cancer carcinomas. c-erbB-2 protein (c-erbB-2 score > 1) was overexpressed in 10/73 cases (14%) and EGF-R (EGF-R ratio > 1) in 42/73 cases (58%). c-erbB-2 overexpression was correlated with tumour size (P < 0.02) and lymph-node involvement (P = 0.05) whereas EGF-R overexpression did not correlate with any of the variables tested. The relative risk of relapse was respectively 1 vs 4.5 (P = 0.001) for patients with a negative (0-1) or positive (> 1) c-erbB-2 score and 1 vs 3 for patients with an EGF-R ratio < or = 1 and > 1 (P = 0.03). Moreover, c-erbB-2 protein overexpression is more specifically an early factor of poor prognosis whereas EGF-R overexpression is a long-term factor of poor prognosis. Patients with an early good prognosis (c-erbB-2 score = 0-1) are found to relapse with time when EGF-R is overexpressed. In a multivariate analysis including axillary lymph-node status, histological grade, tumour size, ER status, c-erbB-2 score, EGF-ratio and hormonal treatment, c-erbB-2 overexpression was the most powerful parameter (P = 0.001) followed by EGF-R overexpression (P = 0.02). We concluded that, in our series, the combined determination of c-erbB-2 protein and EGF-R appeared to be a prognostic indicator whereby both early and long term prognosis could be determined in breast cancer patients.

To date, no five year survival rates have been reported for patients with hepatic metastases (HM) from breast origin treated by chemotherapy or hormone therapy. This study was done to evaluate whether or not surgical excision of such metastatic disease associated with chemotherapy has any effect on such a poor prognosis. Between May 1985 and September 1988, 22 patients with a diagnosis of isolated (solitary or multiple) HM have been surgically treated. The therapeutic approach also included systemic preoperative and postoperative chemotherapy. Laparotomy findings for those 22 patients are presented. There were benign hepatic lesions in four patients (four different histologic types) and hepatectomy was done in two patients. Diffuse metastatic disease contraindicated any attempt at hepatic resection in six patients. Hepatectomy was possible in 12 patients. There was no postoperative mortality and minimal morbidity. One-half of the patients with metastases had one or more positive lymph nodes at the hepatic pedicule. Median survival time for 12 patients treated by hepatectomy was 37 +/- 9 months after hepatectomy and 42 +/- 3 months after the discovery of HM. Eleven patients had other metastases after an average period of 11.8 months after hepatectomy, and the liver was the first site of recurrence in eight. One patient underwent a hepatectomy twice. Two patients were free of disease 29 to 46 months postoperatively in spite of poor prognostic features on the excised specimen. Although the median survival time was two times better than with usual treatment, we believe this procedure is of doubtful benefit. In this situation, hepatectomy acts as cytoreductive surgical treatment, with the main limiting factor being the relatively low effectiveness of chemotherapy. This type of therapy can be applied only to a restricted number of patients, and if we decide to proceed with this study, we will have to modify the protocol of chemotherapy radically.

A group of 74 patients with advanced breast cancer received elliptinium as second- or third-line treatment (100 mg/m2/week). The objective response rate was 19% (30% in soft tissue metastases), lasting from 3 to 12 months. This drug appears to have no marrow toxicity. Mild to moderate nausea and mouth dryness were the most frequently encountered side effects. Hemolysis occurred in five patients who had an IgM antibody and represents the dose-limiting toxicity. Cumulative renal toxicity (World Health Organization, grade 2) was observed in one of ten patients who had received greater than 2000 mg of elliptinium.

Five year survival of 683 mammary carcinomas would confirm the prognostic value of T.N.M. classification (UICC), of tumor particular characteristics (size, fixation to neighbouring structures) and presence or absence of clinical nodes. A clinical-histological relationship was studied for axillary nodes: in our experience, clinical determination is more reliable for estimation of N0 and N2 than N1. Three groups of age were considered; the age, T and N corrected five year survival show a higher mortality for patients older than 60 years with T3-T4, N greater than 0 carcinomas. The study of this prospective computerised register confirms the prognostic value of developping growth tumors (PEV) described by P. Denoix. In fact, inflammatory carcinomas (PEV 2-PEV 3) show a poor 5 year survival and PEV 1 is an intermediate pronostic group between stable and inflammatory carcinomas. PEV 1 was showed to be an independant clinical factor from T and N characteristics.

Estrogen receptors measurement was assayed in human mammary tumors as well as corresponding fine needle aspiration biopsies (95 cases). Correlations between these two determinations were highly significant just as correlations between aspiration biopsies of the same tumor. Some factors may disturb the quality of aspiration biopsy results particularly: 1) a low number of tumoral cells expressed by the cell density, 2) ratio: sample weight-cytosol volume lower than 1/17 corresponding to a too grent dilution, 3) a sample weight lower than 20 mg.

The determination of progesterone receptors (RP) was performed on 80 benign and malignant human breast tumors with a single saturating dose method (10 nM) using dextran-coated charcoal (PR-Bio) and an enzymo-immunoassay (PgR-EIA). There was a significant correlation between the 2 methods qualitatively (P less than 0.001) and quantitatively (r = 0.79). However the results were significantly higher using the PgR-EIA method than the PR-Bio method (P = 0.04) with a regression line Y = 0.81 x +0.58.

The results of 2 chemotherapeutic regimens used in 170 cases of inflammatory breast cancer were compared with those obtained in 60 historical controls treated with radiotherapy and hormonal therapy. Inflammatory breast cancers could be divided into evolutive phase 2 with limited signs of inflammation and evolutive phase 3 where inflammation involved the whole breast. The 60 controls had been treated between 1967 and 1974 with radiotherapy (45 Gy plus an extra dose of 20 or 30 Gy); premenopausal patients underwent ovarian irradiation. The 91 patients treated with regimen A between 1976 and 1980 received a DVM-type induction chemotherapy (doxorubicin 40 mg/m2 on day 1, vincristin 1 mg/m2 on day 2, and methotrexate 6 mg/m2 on days 3, 4, 5) every 3 or 4 weeks, and a VCF-type maintenance chemotherapy (vincristin 1 mg/m2 on day 1, cyclophosphamide 200 mg/m2 on days 2, 3, 4 and 5-fluorouracil 300 mg/m2 on days 2, 3, 4) every 4 weeks. Premenopausal patients had their ovaries irradiated; postmenopausal patients received tamoxifen. The therapeutic sequence was: 3 DVM - 45 Gy - DVM - 15 Gy - 4 DVM - 4-12 VCF. The 79 patients treated between 1980 and 1982 with regimen B received a DVCMF-type induction therapy (doxorubicin 50 mg/m2 on day 1, vincristin 0.6 mg/m2 on day 2, 5-fluorouracil 300 mg/m2 on days 3, 4, 5, cyclophosphamide 200 mg/m2 on days 3, 4, 5 and methotrexate 10 mg/m2 on days 3, 4, 5) every 4 weeks. Hormonal therapy was the same as with regimen A. The sequence was 3 DVCMF - 45 Gy - DVM - 20-25 Gy - 4 DVM - 4-12 VCF. The survival rate at 3 years was 42% in controls, 53% in regimen A patients and 74% in regimen B patients (P less than 0.05). The relapse-free survival rates in these three groups at 3 years were 15%, 32% and 54% respectively (P less than 0.0008). These results suggest that a multidisciplinary approach and initial chemotherapy are useful in this type of breast cancer. The value of prolonged maintenance treatment is discussed.

Cytosolic receptors for estrogens and progesterone are studied using an exchange method in various types of benign breast diseases: fibroadenomas, fibrocystic mastosis, phylloid tumors and gynecomastias. The results show clearly that, contrary to breast carcinomas, receptors are generally not present in benign tumors. These results are statistically significant for all the women studied. Studying the pathological aspects of the tumors, it can be noted that the presence of receptors, is correlated with proliferation forms with large epithelial components. Furthermore, these results show that receptors are not found in gynecomastia. In conclusion, the physician should follow up very carefully the patients with a benign tumor, when hormono-receptors are present.

We have performed a quantitative analysis of steady-state levels of ER-mRNA for 88 untreated, primary breast carcinomas. We compared the amount of specific mRNA with the amount of ER receptor measured, through ligand binding activity, by calculating the ratio R = [ER-protein/ER-mRNA]. This analysis showed that the relative level of ER-mRNA displayed a large range of values partly related to the concentration of ER-protein. We found a greater percentage of tumors with a high R ratio value in the tumor population containing elevated levels of ER-protein. A statistical analysis performed on a homogeneous population of 63 patients shows no correlation between the R ratio, lymph-node involvement and histological grade. However, R appears to be significantly related to the risk of relapse within a relatively short period of time following the first observation. An R value higher than 1.5 appears to constitute a significant and early prognostic factor of recurrence (P = 0.003).

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.

The authors present the results obtained from a series of 511 operable adenocarcinomas (were excluded sarcoma, non infiltrating carcinoma and tumours too small for dosage). Estrogen (ER) and progesterone (PR) receptors were determined on the cytosol with a single saturating-dose method (5nM). The cut-off between positive and negative tumours was 100 fm/g tissue with a border area (100-200 fm/g). Correlation between ER, PR and the followed histological characters were studied: 1) Anatomic size of the tumour: no correlation was found. 2) Histological type: there was a significant correlation (p less than 0.001) between ER, PR and current histological types: among the infiltrating ductal carcinoma, the highly differentiated ones were more often ER+, PR+ (69%) than the atypical one (33%). This correlation remained according to the hormonal status of the patients. The particular types but infiltrating lobular carcinoma were mainly without receptors. 3) Histological grading: there was a significant correlation (p less than 0.001) between this character and the (ER, PR) rate of the tumour: 25% of the tumours of grade III were (ER+, PR+) against 57% of the grade I. As for the histological type, this correlation remained according to the hormonal status of the patients. 4) Stromal reaction: there was a significant correlation between (ER, PR) and inflammatory reaction (p = 0.002) or elastosis (p = 0.002) respectively. Inflammatory reaction was more often reported in tumours without receptors (73% in ER-, PR- tumours against 56% in ER+, PR+ ones). On the opposite, elastosis was correlated with the presence of receptors (52% in ER+, PR+ tumours against 34% in ER-, PR- ones). 5) Lymph-nodes involvement: no correlation was found with hormonal receptors (47% ER+, PR+ in the N- cases against 48% in the N+ cases).

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.

The authors study estrogen (RE) and progestogen (RP) receptors by an exchange technique in 8 cases of male breast carcinoma and 7 cases of gynaecomastia. Tumours are considered receptor positive when the binding sites concentration exceeds 100 fmol/g tissue. Using this as a base all the carcinoma are RE+ and 7/8 are RP+. Gynecomastia are always RE- and RP- except for one case which is RP+. RE and RP levels are correlated with the degree of differentiation of the carcinoma, as determined histologically.