Thermorhythmometry of the breast: a review to 1981.
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Biomedical subjects
Publications and source records attributed to K Griffiths.
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Quantitative values if oestradiol receptor were determined in the primary breast cancer of 526 patients, 106 of whom have so far required hormonal therapy for metastatic disease (premenopausal patients-oophorectomy; postmenopausal patients-tamoxifen 20 mg twice daily). The rate of response to treatment was significantly higher in patients with receptor-positive primary cancers, and the likelihood of response further increased in proportion to the measured receptor concentration. Preliminary data also suggest that patients with high receptor values in the primary tumour will enjoy a longer remission than those with low measured values. Assays of oestradiol receptor were also carried out on biopsy specimens of accessible metastases, largely skin and lymph-node recurrences, in 24 patients who were treated mainly with local measures. Receptor status was the same in both the primary and the secondary tumour in only 18 patients.
Oestrogen receptor status was related to survival in 414 patients with primary breast cancer. Women with oestrogen receptors in their tumours survived significantly longer than those without receptors; this was true for both premenopausal and postmenopausal women and also when the patients were subdivided into those with and without axillary metastases. Patients with axillary metastases and no oestrogen receptors in their tumours had the worst prognosis, while women with axillary metastases and oestrogen receptors had a death rate similar to that of women with no axillary metastases and no receptors. Patients without oestrogen receptors and with no axillary metastases were identified as a high-risk group, and it would seem appropriate to include such patients in future trials for adjuvant therapy in early breast cancer.
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The immunocytochemical detection of four pituitary protein hormones in tissue from 13 patients with benign prostatic hyperplasia has been described. There have been marked differences in the distribution and intensity of reaction product attributable to the various hormonal antisera. The intracellular presence of endogenous prolactin and FSH in the epithelial cytoplasm has been suggested together with the stromal localization of growth hormone and prolactin. Minimal diffuse staining over most cellular components was observed with the LH antiserum. This technique has provided an invaluable means of studying the potential involvement of pituitary protein hormones in the control of prostatic function and disease.
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The oestrogen receptor (RE) status of the primary tumour has been assessed in 466 of a consecutive series of 550 patients with primary operable breast cancer. All patients were followed up (without treatment) until the development of recurrence or metastases. Distant metastases have so far occurred in 124 patients and 82 have had symptomatic local or regional recurrence. A significant correlation exists between the RE status of the primary tumour and subsequent patterns of metastasis. Symptomatic metastases to regional lymph nodes are more common with RE- cancers. There is no significant difference in either time of onset or total incidence of distant metastases between patients with RE+ and RE- tumours. Distribution of distant metastases is influenced by RE status: RE+ tumours tend to recur in bone, RE- tumours show affinity for viscera.
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Estrogen receptors have been assayed in a series of primary breast cancers from postmenopausal women; 59% of which were estrogen-receptor positive. These patients survived for a significantly longer period of time than those whose tumors were estrogen-receptor negative. The effect of estrogen-receptor status was only seen (and then markedly accentuated) in patients who had lymph-node invasion at the time of mastectomy. Such determinations also appear to be of value in preselecting those patients who, on recurrence, will benefit from tamoxifen therapy.
Circadian breast skin temperature rhythms were characterised throughout the menstrual cycle, for various locations on the left breast of ambulatory women. All subjects exhibited highly significant circadian rhythms (P less than 0.001). Changes in rhythm parameters, such as the mesor, amplitude and acrophase, were observed during the menstrual cycle. No consistent trend in these rhythm parameters was observed between subjects in relation to menstrual cycle stage. Experimental and statistical techniques used to characterise circadian rhythms in pre-menopausal women were applied to a post-menopausal woman with primary breast cancer. Comparison of rhythm parameters associated with the tumour area and corresponding site on the contralateral breast showed abnormal thermal characteristics such as elevated mesor values, decreased amplitude as well as changes in the timing of the acrophase. These properties may be exploited for the early detection of breast cancer. The project also involved the design and testing of an ambulatory device, known as the 'chronobra', for the measurement of breast skin temperature. The performance of the chronobra was in close agreement with reliable, conventional equipment. The chronobra now allows studies of breast skin temperature rhythms associated with breast disease to be extended.
The specific retention of androgens and oestrogens by cytoplasmic components of human ovarian tumours was investigated. High-affinity, low-capacity binding of androgens was observed in 88% of tumour specimens and oestrogen binding in 32%. Retention of oestrogens did not occur in the absence of androgen binding. The androgen-binding component, of sedimentation coefficient 7.5-8.5S, showed specificity for 5 alpha-dihydrotestosterone and 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881). In some instances, competition for R1881-binding sites indicated the presence of progesterone receptor-like binding. The data presented suggest strongly the existence of androgen and oestrogen receptors in some ovarian tumours and may be relevant to histopathological classification and therapeutic rationales.
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A specific radioimmunoassay has been developed for diethylstilbestrol (DES), using an antiserum raised against DES monocarboxymethyl ether and a tritium-labeled radioligand. Prior to radioimmunoassay, a fraction enriched in DES is obtained from a dichloroethane extract of plasma using Sephadex LH-20. The specificity of the assay is good, and the sensitivity (130 pg/ml) is adequate for accurate determination of DES in plasma from prostatic cancer patients treated with the drug. The precision is satisfactory, with an interassay coefficient of variation of approximately 10% at concentrations of approximately 1 ng/ml, and the blank values are negligible. Excellent agreement (r = 0.96) is observed between data obtained by radioimmunoassay and those obtained by a procedure using gas chromatography-high-resolution mass spectrometry. DES concentrations in the plasma of six treated (1 mg DES three times daily) patients were in the range 0.15 to 6.0 ng/ml. Increases in plasma concentration were observed within 2 hr of administration, with secondary rises occurring 5 to 6 hr later. Plasma testosterone concentrations were low in four of the patients; in a single subject, relatively high levels of testosterone were further elevated following administration of luteinizing hormone-releasing hormone.
The performance of routine analytical laboratories is assessed, inter alia, by the use of appropriate internal quality control techniques. Despite evidence that the cumulative sum technique is generally superior to Shewhart-type control charts and many others, its use has been limited by the popular misconception that it is inferior to Shewhart's in detecting large variations and/or outliers in quality control data. The application of computer simulation methods has enabled us to answer this criticism and has provided the basis for further improvements in the design of the appropriate control scheme for general use in clinical chemistry.
For a minimum of 3- months, 250 women who underwent mastectomy for primary breast cancer have been followed up. ER status has had a pronounced effect upon disease-free interval and survival: in patients with node involvement ER-positive (ER+) tumors carry a better prognosis. Of patients with ER-positive primary tumors, 43% underwent objective response to their secondaries for a minimum period of six months. This compares with a response of only 18% for ER-negative (ER-) tumors. In patients who had previously received endocrine therapy and on relapse were treated with cytotoxic chemotherapy, objective response rate to chemotherapy was better in patients in whom the primary tumor had been ER-, but not significantly so.