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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.

Pamidronate is a potent biphosphonate which modulates tumour-induced osteolysis (TIO) by inhibiting osteoclast-mediated bone resorption. In a phase II trial, 69 breast cancer patients with symptomatic progressive bone metastases were given infusions of pamidronate 60 mg over 1 or 4 h every 2 weeks for a maximum of 13 infusions or until progressive disease (PD) at any site. No other systemic anticancer therapy was allowed. Pain was measured using a visual analogue scale, mobility using a detailed eight-point questionnaire and analgesic intake using a six-point scale. Improvements in pain, mobility and analgesic scores occurred in 61, 50 and 30% of patients, respectively, with 33, 21 and 16% achieving a 40% improvement for > or = 8 weeks. At trial discontinuation, baseline levels of pain and mobility had improved by 27% (P = 0.001) and 20% (P = 0.004), respectively, despite a one category reduction in analgesic intake in 27% of patients. Using this relatively high dose of pamidronate, symptomatic response was independent of the number of bone metastases and also of infusion rate. The infusions were well tolerated with no major toxicities reported. Pamidronate infusions provide useful palliation for breast cancer patients with symptomatic bone metastases.

Recently, it was found that, among post menopausal breast cancer patients receiving no adjuvant therapy, the highest oestrogen receptor (ER) levels (ER++) as opposed to the intermediate ER levels (ER+) indicated a poorer prognosis in terms of recurrence-free survival (Thorpe et al. Eur J Cancer 1993, 29A, 971-977). In the present study, we confirm, in a series of 218 node negative, postmenopausal patients in whom ER was determined using a one-dose saturating method, that ER+ tumours have a more negative effect on disease-free survival (DFS) than ER+ tumours (P = 0.02). In another series of 87 ER positive, postmenopausal patients, we found a significant correlation (P = 0.04) between the ER level and ER+R ratio (ER protein/ER-specific mRNA): the higher the ER level, the more numerous the high ER+R ratio cases (ER+R > 1.5), reflecting an imbalance between the ER protein level and ER-specific mRNA. From these results, we hypothesise that high ER levels related to a high ER+R ratio suggest the presence of a modified ER gene product.

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.

Purpose: A phase I/II trial of vinorelbine (VRL) administered by continuous infusion (CIV) was conducted in advanced breast carcinoma (ABC) patients to determine the maximum-tolerated dose (MTD) and to evaluate the toxicity pattern and antitumor activity of this alternative administration schedule to the currently recommended weekly short intravenous (IV) administration., Patients and Methods: Between February 1990 and July 1991, 64 consecutive, eligible patients with ABC were treated; 33 had received one or two previous palliative chemotherapy combinations and 31 had not received chemotherapy for metastatic disease. VRL was administered, after an initial IV bolus of 8 mg/m2 on day 1, by a 4-day CIV at five different 24-hour dose levels (DLs) to be repeated every 21 or 28 days: DL1, 5.5 mg/m2; DL2, 7 mg/m2; DL3, 8 mg/m2, DL4, 9 mg/m2; and DL5, 10 mg/m2., Results: The limiting noncumulative toxicity was neutropenia, with the MTD established at 8 mg/m2 bolus plus 10 mg/m2/d for 4 days (total dose per cycle, 48 mg/m2). At DL3 and DL4, we observed mucositis (14% of patients; five percent of cycles > grade 2), alopecia, and asthenia. By contrast, neurotoxicity was minor. The toxicity was otherwise predictable and manageable. Pharmacokinetic data obtained at DL1 and DL3 showed a mean VRL plasma concentration of 967 +/- 331 ng/mL after the initial 8 mg/m2 IV bolus dose, which declined rapidly thereafter to reach mean steady-state levels of 12 ng/mL (n = 5) for the 30-mg/m2 dose and 8 ng/mL (n = 2) for the 40-mg/m2 dose. These levels were maintained over the 96-hour CIV. The mean residence time (MRT) was 29 +/- 7 hours (terminal half-life [t1/2], 23 hours), the total-body clearance (CL) was 24 +/- 11 L/hr/m2, and the volume of distribution at steady-state (Vss) was high at 1,832 +/- 359 L/m2. Two patients achieved a complete response (CR) and 21 a partial response (PR), for an objective response rate of 36% (95% confidence interval [Cl], 23 to 49). The median duration of response was 6 months. The median survival duration was 24 months (range, 3 to 37). A relationship between given dose-intensity and objective response rate was found, with an overall response (OR) rate of 13.3% (two of 15) for 8 to 10 mg/m2/wk, 35.4% (11 of 31) for 10 to 12 mg/m2/wk, and 55.5% (10 of 18) for 12 to 14.5 mg/m2/wk., Conclusion: This trial, while confirming VRL activity in ABC, shows the feasability of a CIV administration schedule. A decrease of the administrated total dose per 3- to 4-week cycle to less than the weekly schedule with the same therapeutic activity suggests a better therapeutic index. The data are also suggestive of a dose-response relationship and a dose-intensity/activity correlation.

Background: The response to endocrine therapy is not entirely predictable from the estrogen receptor (ER) and progesterone receptor (PgR) status of primary breast tumors. The authors previously proposed a new prognostic factor, ER.R, which was based on both ER protein and mRNA levels. A previous analysis of 88 primary breast carcinomas showed that ER.R permits the identification of a subset of ER-positive women with a higher risk of early relapse. The purpose of the present study was to confirm the prognostic significance of ER.R., Methods: Estrogen receptor protein levels were determined for 171 patients with primary breast cancer either by radio-ligand binding assay (ER-LBA) or enzyme immunoassay (ER-EIA). Estrogen receptor, pS2, and c-erbB-2 mRNA were measured by Northern blot analysis., Results: ER.R factor is determined by calculating the ratio of the values (ER protein in fentomoles per milligram of total proteins) to (ER mRNA in picograms per 4 micrograms of total RNA). A cutoff value of 1.5 (protein levels measured by ER-LBA) or 3 (protein levels measured by ER-EIA) discriminate the two ER.R1 (lower ratio) and ER.R2 (higher ratio) subgroups, which present a significantly lower and higher risk of early relapse, respectively. No association was found between ER.R status and either PgR status or c-erbB-2 and pS2 expression. According to a Cox multivariate analysis for disease free survival, the two stronger factors in predicting a poor prognosis were c-erbB-2 overexpression and ER.R2. In the present analysis, ER.R2 was a stronger predictor of recurrence than was ER negativity., Conclusions: In accordance with the authors' first published data, the analysis of a larger population with a longer follow-up showed that ER.R2 keeps its significance to predict a poorer outcome for a patient, regardless of which assay was used to quantify ER.

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.

Ninety-nine patients presenting with non-metastatic inflammatory breast cancer were treated with an alternating protocol of radiotherapy and chemotherapy. The alternating schedule consisted of 8 courses of combined chemotherapy, including doxorubicin, vincristine, cyclophosphamide, methotrexate and 5-Fluorouracil, and 3 series of loco-regional radiotherapy delivering a total dose of 65 to 75 Gy to the breast tumor, 65 Gy to the axilla, and 50 Gy to the supraclavicular and internal mammary chain lymph nodes. Radiotherapy was started after the third course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy-five percent of patients were in complete remission at the end of this induction treatment. The 3-year local control was 72% and the 3-year overall survival rate was 70%. An isolated local recurrence was observed in only 4% of patients. Approximately one-half of patients developed distant metastases. These results show that alternating radiotherapy and chemotherapy schedules deserve further investigation in locally advanced breast cancer.

We recently defined a new early prognostic factor, the ER+(R) status, which permits the discrimination of a group presenting a high risk of early relapse among the ER+ patients. This group was referred to as ER+(R2) in contrast to ER+(R1) which corresponded to the group of ER+ patients having a lower risk of early relapse. Taking into account the whole population including the ER- and inflammatory tumours, we have extended this view and showed that ER+(R) status is a significant predictor of disease-free survival. Determination of c-erbB-2 mRNA levels in the same series of tumours showed that high expression of c-erbB-2 mRNA is significantly correlated with ER-, inflammatory tumours and with lymph nodes involvement. Moreover, a multivariate analysis showed that c-erbB-2 mRNA overexpression was a significant predictor of early relapse (P = 0.02), as significant as ER negativity and ER+(R2). For ER+ patients a high level of c-erbB-2 mRNA constitutes a higher risk of relapse for both ER+(R1) and ER+(R2) patients. However, in the case of ER- patients, early relapses were strongly correlated with c-erbB-2 overexpression. The counterpart of this observation is that ER- patients with no overexpression of c-erbB-2 constitute a group with a relatively good prognosis.

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.

Oestrogen (RE) and progesterone (RP) cytosolic receptors have been studied in 59 clinically inflammatory tumours of the human breast. The results were compared to those obtained in a series of 496 operable tumours. A single saturating dose of oestradiol for RE and R 5020 for RP was used and the cut-off between negative and positive tumours was 100 fmol/g tissue. A significant difference was seen (P less than 0.02) between the 2 classes of patients: (RE-, RP-) tumours were commoner among clinically inflammatory tumours (48%) than among operable ones (28%), independently of menopause. Concerning the histological type (based on an assessment of differentiation) and the histological grading (Scarff and Bloom) there was a significant difference (P less than 0.001) between the 2 populations of tumours. No significant difference was found in the distribution of RE and RP among the 3 histological types, whereas a significant correlation existed between histological grading and RE (P less than 0.02). Finally, patients with RE+ clinically inflammatory tumours constitute a lower risk group, especially when they are free of metastases at the time of diagnosis. The presence of RE therefore seems to indicate, as in the operable tumour group, a favourable prognosis.

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.

We report the largest series of induction chemotherapy for inflammatory breast carcinoma (IBC). Results of two chemotherapy protocols with radiation therapy (RT) (170 patients) are compared with results with radiation alone (60 patients) in the treatment of this disease. From 1973 to 1975, 60 patients (control, group C) received RT (45 Gy and 20 to 30 Gy boost) and hormonal manipulation. From 1976 to 1980, 91 patients (group A) were treated with induction chemotherapy: Adriamycin (Adria Laboratories, Columbus, Ohio), vincristine, and methotrexate (AVM) and RT on a cyclical schedule; and maintenance chemotherapy: vincristine, cyclophosphamide, and 5-fluorouracil (5-FU) (VCF). From 1980 to 1982, 79 patients (group B) received induction chemotherapy, Adriamycin, vincristine, cyclophosphamide, methotrexate, and 5-FU (AVCMF) and RT on a cyclical schedule and VCF maintenance. Hormonal manipulation was performed in all groups. Disease-free survival at 4 years was 15% for group C, 32% for group A, and 54% for group B (P less than .005 group C v group A, less than .00001 group C v group B, and less than .01 group A v group B). Total survival at 4 years was 42% for group C, 53% for group A, and 74% for group B (P = .17 group C v group A, less than .00001 group C v group B, and less than .001 group A v group B). Clinical assessment of tumor aggressiveness, nodal status, type of chemotherapy administered, and early response to chemotherapy (by third course) were all prognostic factors. There is an important, highly statistically significant benefit in terms of both disease-free survival and total survival observed in patients treated with the addition of chemotherapy compared with radiation alone in IBC.

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.

In a series of 94 human mammary carcinomas, the determination of total estrogen (ER) and progesterone (PR) receptors by a single saturating dose method (5 nM for ER, 10 nM for PR) using dextran-coated charcoal was compared to an immunohistochemical method utilizing ER monoclonal antibody (ER-ICA test). There was a good correlation expressed in positive terms between the ER-ICA test and the biochemical determination of ER (94% of concordance) with a statistical value of P less than 0.01 being found between the concentration of ER (biochemical) and the percentage of labeled cells (ER-ICA). The ER-ICA test complements the ER and PR (biochemical) and is particularly useful for ER determinations on small tumor specimens as no additional tissue other than that from the biopsy is required.

Epidermal growth factor receptor (EGFR), determined by the Scatchard curve method, was found in 22 cases of a random series of 100 patients with breast carcinoma. Two groups of patients were identified, one (n = 16) with a low concentration (0-50 fm/mg protein) of EGFR but with a high affinity (Kd = 3.2 nM), and the other (n = 6) with a high concentration (90-210 fm/mg protein) of EGFR but with a lower affinity (Kd = 6.3 nM). A significant inverse relationship was found between the presence of EGFR and receptors for estrogen (p less than 0.001) and progesterone (p = 0.001). EGFR was found in no (0/8) tumors with Grade I histoprognostic grade, 17% (10/58) Grade II, and 38% (11/29) Grade III (p less than 0.05). EGFR is present therefore in poorly differentiated tumors and associated with other factors of poor prognosis. Our in vivo analyses confirm results found in tissue culture derived from human breast carcinoma cells.

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.

211 patients with various stages of breast cancer were studied by both the CA 15.3 and CEA markers to assess whether the latter may increase the screening sensitivity of the former. While both markers were equally specific, CA 15.3 was seen to be much more sensitive than CEA (p less than 0.0001). Also, the addition of the CEA did not add appreciably (7%) to positive detection by CA 15.3. There appears to be no advantage to including CEA in a marker panel to follow the course of breast carcinoma.

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 have studied Estrogen (RE) and Progestin (RP) cytosol receptors in 379 human breast carcinomas: 281 tumors suitable for surgery, 26 pseudo-inflammatory tumors, 52 metastases and 20 recurrences. They have used an exchange technique with estradiol for RE and a synthetic compound, R 5020, for RP. The results point out that high rates of RE correlate with post-menopausal women and high rates of RP with pre-menopausal women. Tumours are considered receptor-positive when the binding sites concentration exceeds 100 fmoles/g tissue. Using this as a base 32% of the tumors are RE and RP negative. Considering only the positive tumors, 54% contain both receptors, 31% only RE and 15% only RP. The percentages are also given in terms of the hormonal state of the patients. The results are discussed in terms of McGuire's hypothesis that both receptors are necessary to obtain a positive response to hormonal therapy. Correlation between histology and receptors is also discussed.

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 pattern of estrogen (ER) and progesterone receptors (PR) and their relationship to histo- and cyto-pathological parameters has been studied in 97 cases of benign breast disease and benign phyllode tumors (95 women, of whom 76 were premenopausal, and 2 men). Total (cytosolic + nuclear) ER and PR were assayed by a single-saturating dose method using a tris-KCl buffer. The cut-off between positive and negative ER and PR assay was 100 femtomoles/g tissue. All specimens were processed for histological examination: epithelial and fibroblastic proliferation, epithelial/stromal ratio and presence of focal or diffuse hyalinosis. In 33% of the 46 cases of fibrocystic disease one receptor at least was present (13% ER+, 31% PR+). All the 8 cases in which infiltrating epitheliosis was present were PR+ and 4 of them were also ER+. In 72% of the 31 fibroadenomas one receptor at least was present (19% ER+, 71% PR+). In all these cases levels of receptors were lower than in malignant tumors. An inverse correlation between PR + prevalence and fibrohyalinosis was observed; on the other hand a positive relationship between PR + and fibroblastic (p less than 0.001) or epithelial (p less than 0.01) proliferation was found. In all 5 benign phyllode tumors examined PR + were present at a very high level, almost as high as in malignant tumors. Of the 15 other benign breast lesions, all but one (1 hamartoma) were ER- and PR-.

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.

Twenty-two patients with advanced colorectal cancer (CRC) (12 without prior chemotherapy) and fourteen with pretreated breast cancer (BC) were given mitozolomide (MTZ), IV infusion, every six weeks. The starting dose was 90 mg/m2. When it was well-tolerated, dose escalation was done up to 100-115 mg/m2. Toxicity was mild, limited to thrombocytopenia with a median nadir of 1.27 x 10(5) (0.20-4.86). No response was observed in these patients. MTZ, according to these schedule and dosage, does not show activity in human CRC and pretreated BC.

Serum samples taken from children bearing a wide variety of tumors were screened for the presence of circulating antibodies against the cellular tumor antigen p53. There was a significant correlation (p less than 0.001, n = 119) between the presence of such antibodies and the occurrence of cancer; 12% of the sera tested were positive. These sera were derived from children with a wide range of tumor types. In particular, 21% of the sera obtained from children suffering from a B-cell lymphoma contained anti-p53 antibodies. We were not able to establish a correlation between the secretion of p53-reactive antibodies and any other parameters, such as the age or sex of the child, presence of metastasis, stage or prognosis of disease, or treatment regimen. These results therefore show that the development of p53 immunogenicity is associated with a wide range of neoplastic diseases in children, and in particular with the presence of a B-cell lymphoma.

The complete protocol for the treatment of breast cancer at the Institute Gustave Roussy, Villejuif, France, is presented. Treatment is carried out by a multidisciplinary committee dealing with nearly one thousand new breast cancers annually. The protocol is based on initial classification by the T.N.M. system and by characteristics indicating "aggressive biological behaviour". Patients are separated into three broad groups for which the mainstays of treatment are surgery, radiotherapy, and chemotherapy. The rationale and results of the protocol are presented.