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  • Title: The prediction of hormonal dependency of mammary cancer.
    Author: Block GE, Jensen EV, Polley TZ.
    Journal: Ann Surg; 1975 Sep; 182(3):342-52. PubMed ID: 169754.
    Abstract:
    The estrogen receptor protein (estrophilin) was determined in specimens from 359 primary breast cancers and from metastatic tumors of 214 patients. Ninety-eight patients were eventually treated by some form of endocrine therapy: 82 patients were treated by ablative therapy, and 16 by hormonal additive treatment. The records of 81 of the 98 patients whose tumors were characterized for estrogen receptor content and who had received some type of endocrine therapy were reviewed by a peer review group that assessed the objective data for these patients regarding objective remission or failure to treatment. A positive estrophilin determination was defined as receptor content greater than 250 fmole per gram of tumor for premenopausal females and greater than 750 fmole per gram of tumor for postmenopausal and previously castrated patients. Estrogen receptor determinations may be made from tumor specimens as small as 200 mg. Sixty-nine patients underwent some form of ablative therapy. Twenty-seven of these patients were found to have significant receptor determinations. Of those patients in whom a definite determination was made of their post-treatment response, roughly two-thirds experienced objective remissions. None of the 42 patients with negative estrogen receptor determination experienced an objective remission to ablative endocrine therapy. Only one of 6 patients with negative determinations benefited from additive hormonal therapy; 4 of 6 patients with positive determinations benefited from additive therapy. Not all women with receptor containing mammary cancer will respond favorably to endocrine therapy, but those patients whose tumors lack a critical amount of estrophilin have little chance of benefit from either endocrine ablation or hormone administration. The estrogen receptor content of the primary tumor indicates the hormonal dependency of the tumor and may be used to predict the response to endocrine treatment when recurrent disease appears. Less than half of premenopausal patients with mammary cancer and even fewer postmenopausal patients have tumors that respond to endocrine ablation. The level of estrogen receptor protein (estrophilin) in the mammary cancer tissue provides an indication of the hormone dependency of the tumor and may be sued to predict the response to endocrine treatment when recurrent disease appears. Metastatic growths usually have a similar content. This is a report of an investigation of the estrophilin content of specimens of tumors from patients with metastatic and recurrent mammary cancer for correlation with their response to endocrine changes. Primary tumors were also studied for future clinical use if needed. The estrophilin was determined in specimens from 214 metastatic growths and 359 primary breast cancers. The uptake of estradiol in an in vitro system and the blocking effect of specific inhibitors provided a means of distinguishing between estrogen responsive tissues which contained receptor proteins and non-estrogen-responsive tissues which did not contain these receptors. Some form of endocrine manipulation was used in 82 patients. Of these, 69 had ablative therapy. Of the 69, significant receptor levels were present in 27 and 2/3 of them had remissions. Of the 42 with negative e strophilin determinations, none had a remission after ablation. Therefore, the absence of significant amounts of estrophilin in breast cancer tissue indicates that the patient has little chance of responding to endocrine manipulation and should be spared this method. In 16 others, hormonal additive treatment was used. Only 1 of 6 patients with negative determinations benefited temporarily from the additive hormone therapy. Discussion and questions by others followed presentation of this paper. Other hormones as possibly important were suggested. Combining chemotherapy with adrenalectomy was suggested. It was stated that some noncancerous breast tissues also contain estrogen binding proteins. Dr. Block answered questions and added comments. He stated that estrophilin is present in many tissues but in very low amounts. It is a quantitative difference that is important.
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