Epidermal growth factor receptors in breast cancer: comparison of radioligand and immunocytochemical assays.

Epidermal growth factor receptors (EGFR) are part of second generation biological factors that clinicians caring for breast cancer patients wish to evaluate for their prognostic value. This aim requires the standardization of methods: the radioligand assay (RLA) for the quantification of EGF binding sites was performed on membrane pellets from 261 breast cancer samples (ligand binding and hydroxylapatite separation as recommended by the EORTC Receptor Study Group); the immunocytochemical assay (ICA) for the staining of EGFR antigenic sites was performed on fine needle aspiration (FNA) cytology or touch imprints from 97 surgical specimens. The percentage of EGFR positivity by RLA (specific binding higher than 1% of total radioactivity) and the EGFR positive rate by ICA (more than 5% of stained cells) were respectively 43% and 38%. For 61 cases assayed on the same patient both methods revealed a concordance of 85%. Our results show that both methods are complementary and give quantitative data and information on tumor heterogeneity when they are performed in parallel. The next step of this study will be to determine the prognostic value of EGFR in these subpopulations of tumors for the adjustment of adjuvant treatment.

Expression of mdr1 gene in human breast primary tumors and metastases.

Expression of mdr1 gene has been evaluated in 34 tumor samples obtained from breast cancer patients who were classified according to their treatment, and clinical follow-up. No gene amplification was found. mdr1-RNA was never detected in 29 primary breast tumors including 5 samples from patients previously treated by 6 courses of 5-fluorouracil, epirubicin, cyclophosphamide (FEC). On the other hand, mdr1-RNA expression was detected in 1 local recurrence and 2 out of 3 metastases, all of them being treated and exhibiting a poor evolution. A second, untreated local recurrence remained negative. Clinical follow-up for 7 to 48 months in patients receiving chemotherapy showed that absence of mdr1-RNA could not be an accurate factor of satisfactory response to chemotherapy. But, all the patients with detectable mdr1-RNA exhibited a poor evolution and response to treatment. In conclusion, evaluation of mdr1-RNA seemed to be of little interest in primary breast tumors. However, the concomitant presence of an mdr1-RNA and a metastatic phenotype could give a new insight into the relationship between invasive and resistance properties of cancer cells. Such situations would need to be analyzed very carefully for a better utilization of chemotherapy.

Argyrophilic nuclear organiser region counts in locally advanced breast carcinoma treated by chemotherapy before surgery.

The value of argyrophilic nuclear organiser region (AgNOR) counts in assessing histologically the effects of combination chemotherapy given to eleven patients with locally advanced breast cancer before mastectomy was studied. AgNOR counts were significantly reduced (P less than 0.001) in the post-chemotherapy, surgically excised residual tumour specimens compared with the initial diagnostic biopsy specimens. AgNOR counts could be used to monitor the effects of chemotherapy on breast cancer.

[Evaluation of two serum isoenzyme phosphatases as bone metastasis markers]. / Evaluation de deux isoenzymes sériques des phosphatases comme marqueurs des métastases osseuses.

Serum activities of bone alkaline phosphatase (b-ALP) and of tartrate resistant acid phosphatase (tr-ACP) were evaluated in 271 cancer patients; 120 of them had bone metastases (BM) and 151 had none. Correlation coefficients, specificities, sensitivities, negative and positive predicting values were computed. They showed the important contribution that these isoenzymes can bring to the diagnosis of BM in 80 patients with prostate cancer, and to the followup of 191 patients with breast cancer. The assay results were analysed in parallel with bone scan and radiography. They were also compared to those of serum antigens: PSA and PAP for prostate cancer, and CEA and CA15.3 for breast cancer. These results clearly indicate that both isoenzymes are better correlated with BM than antigens, these antigens being markers of the whole tumor burden--primary tumor, metastases, recurrence--whereas b-ALP and tr-ACP are specific markers of bone metabolism.

Isoenzymes of alkaline and acid phosphatases as bones metastasis marker in breast cancer patients.

Bone alkaline phosphatase (B-ALP) and tartrate resistant acid phosphatase (TR-ACP) are markers of osteoblastic and osteoclastic activities respectively. During a period of up to two years, these isoenzymes have been assayed in the sera of 191 breast cancer patients; 80 had bone metastases (BM). In BM bearing patients, B-ALP activity was 261 IU/l and 63 IU/l for patients without BM; TR-ACP was respectively 6.6 and 3.3 IU/l. Specificity and sensitivity were calculated according to several criteria. These isoenzyme serum levels were well correlated with those of two breast cancer markers (CEA and CA15.3) and radiograph.

Phase II trial of idarubicin (4-demethoxydaunorubicin) in advanced breast cancer. The Clinical Screening Group of the European Organization for Research and Treatment of Cancer.

A phase II trial of idarubicin (IDR-4 demethoxydaunorubicin) was carried out in patients with advanced breast cancer. A dose of 45 mg/m2 was given orally once every 3 weeks. A total of 66 eligible patients were entered into the trial, 56 of whom were evaluable for response (65 were evaluable for toxicity at least). Therapeutic activity was demonstrated with an overall objective response rate of 21% (95% CI: 11-32%). When used as a first-line treatment, the response rate was 33% (95% CI: 9-57%) but this dropped to 17% when the treatment was administered after chemotherapy. Nausea-vomiting was the most frequent and severe non-hematological toxicity observed (WHO grade 3-4: 29%). Loss of hair was noticed in 48% of the patients but only 4% suffered from complete alopecia. Moderate myelotoxicity was reported but no cardiac dysfunction was noticed. IDR could be very advantageous as compared to other anthracyclines, due to its simplicity of administration associated with the lack of risk of extravasation or chemical phlebitis and also the possibility of it being able to reduce cardiotoxicity. Even if the equiefficacy of IDR and DXR has not, as yet, been clearly demonstrated, IDR should be chosen with preference to DXR when administration is not suitable.

Simultaneous microscopic and biochemical findings in breast carcinoma. Preliminary results.

Intratumoral protein and glucose phosphate isomerase (GPI) content as well as median nuclear DNA amount were determined in breast carcinoma that could be classified by Bloom's grading. These data were analyzed in comparison with TNM classification. Higher protein contents have been displayed in T2 or N+ breast cancers than in T1 or N- tumors. Bloom's grading is strongly correlated to median nuclear DNA content and to some extent with protein and GPI amount. With these results, we have to think about the value of prognostic cytologic criteria. The relationship between intratumoral protein content and prognostic clinical or histological data requires our attention. This would seem to dictate a need for caution in expressing the results of some variables in function of protein content.