Six-year results of a multimodality treatment strategy for locally advanced breast cancer.

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5-fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow-up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at greater than 9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long-term survival (10 years), excellent local control, but substantial toxicity.

Significance of quantitative assessment of estrogen receptors for endocrine therapy in advanced breast cancer.

The predictive significance of quantitative assessment of estrogen receptors in tumor tissue was analyzed in women with advanced breast carcinoma. Receptor concentration was measured by the 3H-estradiol binding capacity of the cytosol fraction of biopsies taken before initiation of the treatment. The E. O. R. T. C. criteria for the assessment of the patients' response were used. In a total of 34 assessments, 25 biopsies contained receptors; the remaining ones were negative. Objective remission to various endocrine therapies was recorded in only eight of the receptor-positive patients. Responses occurred along the whole scale of receptor concentrations with an apparent crowding in the region of the higher values. Linear logistic regression analysis revealed that among 12 variables of known prognostic value, receptor concentration was the most significant in relation to therapeutic response. Other significant variables were bone involvement and age. Computations yielded formulas that are presented in graph form and provide an estimate of the probability of a given patient to respond to endocrine treatments. On the other hand, the results suggest that all patients are possibly hormone dependent, although to variable degrees. The latter concept has very definite therapeutic implications.

Oestrogen receptors in male breast cancer.

Eleven samples from 7 primary and 4 metastatic male breast cancers were analysed for cytoplasmic oestrogen receptors. Two samples of metastatic cancers were obtained from a same patient 6 months apart. Receptors were assayed by measuring the binding affinity of cytosol fractions for 3H-oestradiol- 17beta. Saturable binding sites were obtained in 6 primary and 1 metastatic cancers. The dissociation constant of the binding reactions were within the range reported for the specific oestrogen receptors from female breast cancers. When present, receptor concentrations varied from 59 to 532 fmoles/mg tissue protein. Competition studies of the binding of 3H-oestradiol- 17beta by excess amounts of unlabelled steroid hormones or antihormones revealed that the receptors were specific for oestrogens and antioestrogens. By all these criteria, receptors from male mammary cancer were identical to those from female breast cancer. Chromosome analysis was performed in 6 patients. All had normal 46 XY male pattern indicating that no conspicuous genetic abnormalities such as those of the Klinefelter syndrome seemed responsible for the presence of the receptors.

Oestrogen receptors in breast cancer: a changing concept.

Oestrogen receptors were found in 156 (73%) out of 214 primary breast cancers and in 98 (58%) out of 168 metastatic deposits. These proportions reached 82% and 70% respectively in the second half of the study. Receptors were not found in samples of normal breast tissue but small amounts were present in tissue from some hyperplastic lesions and in male gynaecomastia. Receptor concentrations in the malignant samples were evenly distributed over a wide range of values, suggesting that even "negative" tumours might contain trace amounts undetectable by the method used. Each tumour was characterized by a given level of receptor concentration. In most cases the amounts found in the invaded axillary nodes and their corresponding primary tumours were the same. We suggest that quantitative rather than qualitative assessment should provide an appropriate criterion for studies of biochemical and clinical correlations.

[Hormonal receptors of malignant breast tumors]. / Les récepteurs hormonaux des tumeurs malignes du sein

Tissue samples from 166 primary and 136 metastatic breast cancers were analysed for the presence of estrogen receptors. It was found by measuring the affinity of the cytoplasmic fraction of these samples for 3H-estradiol-17 beta that receptors were present in 72 p. 100 and 54 p. 100 of primary and metastatic cancers respectively. Receptor concentration varied among sample in an apparently continuous distribution from zero to 2,080 femtomoles per mg tissue protein. This suggests that mammary tumors are different from one another more in a quantitative than in a qualitative way. Detectable amounts of receptors were found in samples from mammary dysplasia, fibroadenomas as well as from one papilloma; none was detected in samples from non-tumorous mammary gland, nipple areola or skin. At mastectomy, no correlation was found between presence or absence of receptors in the primary tumors, and presence or absence of metastatic axillary nodes. On the other hand both the primary and its axillary metastases almost always displayed the same characteristic as far as presence or absence of receptors was concerned. Analysis of clinical studies reported seems to indicate that women with advanced breast cancer respond in a fair proportion of cases to various endocrine treatments when tumor tissue biopsies contain estrogen receptors whereas the probability of a response is very low in their absence.