Jean-Claude Delarue

Epidermal growth factor receptor in human breast cancers: Correlation with estrogen and progesterone receptors

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<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<0.05). EGFR is present therefore in poorly differentiated tumors and associated with other factors of poor prognosis. Ourin vivo analyses confirm results found in tissue culture derived from human breast carcinoma cells.

Epidermal growth factor receptors and prognosis in primary breast cancer.

A retrospective study was performed on 109 human breast tumors stored in liquid nitrogen in order to assess the prognostic value of epidermal growth factor receptor (EGF-R) (median patient follow-up 5 years). A significant inverse relationship was observed between EGF-R and both estrogen (ER) and progesterone receptors (PR). Univariate analysis showed a trend towards a shorter metastasis-free survival both in the overall population and in node-negative patients with EGF-R positive tumors. Multivariate analysis of the overall population showed that lymph-node involvement and PR status were the only significant variables in predicting metastasis-free survival. However, in patients receiving no adjuvant treatment (hormone therapy or chemotherapy), EGF was the only significant variable in the multivariate Cox analysis. No c-erbB-1 amplification was detected in these tumors.

Estrogen receptors (ER) in human breast cancer. The significance of a new prognostic factor based on both ER protein and ER mRNA contents

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.

Is the negative prognostic value of high oestrogen receptor (ER) levels in postmenopausal breast cancer patients due to a modified ER gene product

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.

Markers in breast cancer: Does CEA add to the detection by CA 15.3?

Abstract211 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<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.

Use of a Polyclonal Antibody for the Determination of the Prognostic Value of c-erbB-2 Protein Over-Expression in Human Breast Cancer

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.

Inflammatory Tumors of the Human Breast: Determination of Estrogen and Progesterone Receptors

The clinically inflammatory tumors are considered to be very severe carcinomas characterized by a particularly low rate of survival at 5 years [6, 14]. In the present study, we have simultaneously determined estrogen receptors (ER) and progesterone receptors (PgR) in these tumors and compared the results with those obtained in primary operable carcinomas. The prognostic value of ER has also been studied.

Characterization of two monoclonal antibodies against the COOH-terminal part of the human epidermal growth factor receptor and potential clinical use

Two monoclonal antibodies of the IgG2 subclass, designated A 01 and B 11, were prepared against two synthetic peptides corresponding to the COOH-terminal sequence of the human epidermal growth factor receptor (EGF-R), in order to detect EGF-R in a radioimmunometric assay and by immunohistochemistry. Characterization of these Mabs showed that they recognized two different eptiopes on the original peptides with Kd of 1.7 x 10(-8) M and 1.3 x 10(-7) M, respectively, without crossreaction. The A 431 antigen recognized by A 01 and B 11 had an apparent molecular weight of approximately 170,000 and was able to specifically link to EGF. Thus, A 01 and B 11 are directed against an antigenic site on the human EGF-R. With Western blot analysis and immunostaining, A 01 was shown to be EGF-R specific. In addition to the EGF-R, B 11 recognized two unidentified soluble proteins present in the cytoplasm of the SKBR-3 cell line but different from the c-erb B-2 oncoprotein expressed by these cells. Mabs A 01 and B 11 were used in an IRMA for the determination of EGF-R using the A 431 cell line as a source of EGF-R. Mab A 01 was also shown to be a useful tool for immunohistochemical detection of EGF-R.

Human breast tumors: A comparison between the biochemical method of measuring estrogen and progesterone receptors and that of an immunohistochemical method

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.