Summary An antibody, 21 N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein has been used immunocytochemically in a retrospective study of formalin fixed paraffin embedded breast biopsies. Fourteen out of 103 infiltrating ductal carcinomas exhibited positive membrane staining. Fifty-four of these tumours had lymph node involvement of which nine contained stained cells. These were all cases where the primary tumour was positive. In this series there was no correlation between c-erbB-2 overexpression and lymph node status. In five of the positive cases studied there was an associated in situ component which was also positively stained. Ten out of 24 pure intraduct carcinomas showed membrane staining, but none of the 149 benign conditions studied, which included 22 radial scars and 13 cases of atypical ductal proliferation, demonstrated the pattern of staining associated with overexpression. It is concluded that the c-erbB-2 protein is overexpressed in a minority (-14%) of infiltrating ductal carcinomas and only in cells that are cytologically malignant. Overexpression of c-erbB-2 is considered in relation to pathogenesis.
Summary The influence of the prototype aromatase inhibitor Aminoglutethimide (AG) and its analogue Rogletimide (RG) on peripheral aromatisation were investigated in 13 postmenopausal women with advanced breast cancer. Seven patients received AG 1,000 mg daily plus Hydrocortisone (HC) cover and six received.RG as dose escalation of 200 mg bd, 400 mg bd and 800 mg bd. In vivo aromatase inhibition was investigated using the double bolus injection technique with [4-14C] oestrone ([4-4C]E1) and [6,7-3H] androstenedione ([6,7-3H] 4A) followed by a 96 h urine collection. The labelled urinary oestrogens were separated and purified by chromatography and HPLC. Plasma oestradiol (E2) was also measured.AG Hormonal manipulation is an effective treatment modality in 30% of post-menopausal women with advanced breast cancer (Stoll, 1981). The majority of endocrine treatments for metastatic breast cancer are aimed at oestrogen deprivation of the cancer cell, either by oestrogen receptor blockade as with tamoxifen or by inhibition of peripheral oestrogen production by the aromatase system of enzymes. Peripheral aromatisation is the main source of post-menopausal oestrogens (Grodin et al., 1973). Its inhibition was first shown to be an effective clinical treatment by (Hall et al., 1969) using Aminoglutethimide (AG) and since by many others (Santen et al., 1981;Harris et al., 1982). AG is still the only widely available and used aromatase inhibitor. However at doses greater than 500 mg a day its inhibition of cholesterol side chain cleavage in the early steps of steroidogenesis and the partial blockade of Ilp-, 18-and 21-hydroxylases in the adrenal necessitates its administration in conjunction with hydrocortisone to avoid hypoaldosteronism (Lonning & Kvinnsland, 1988). AG has other side effects ranging from self limiting rashes to serious bone marrow suppression. Neuro-toxicity can be a particular problem in the elderly, limiting its use in a group of patients ideally suited to aromatase inhibition for palliating advanced disease. These problems have encouraged the development of new, more specific second generation aromatase inhibitors (Goss et al., 1986;Harris et al., 1988;Stein et al., 1990aStein et al., , 1990bDowsett et al., 1990).Rogletimide (RG) is a non-steroidal analogue of AG which during early development showed similar in vitro aromatase potency (Foster et al., 1985). In vivo animal studies revealed a lack of toxic metabolites and CNS effects and volunteer/patient studies confirmed its ability to suppress E2 (Haynes et al., 1991). RG did not inhibit cortisol production either by interaction with cholesterol side chain cleavage or with the 21-and 11P-hydroxylases and therefore does not require cortisone replacement . Pharmacokinetic data showed that RG induced its own hepatic metabolism similar to AG Patients, materials and methods
PatientsThe protocol was approved by the hospital ethical committee and all patients gave informed consent. ARSAC clearance was obtained for the use of radio-isotopes in patients. Thirt...
Xeromammography did not enhance the diagnostic accuracy of clinical examination and aspiration cytology in patients presenting with a breast lump and, as a procedure with potential hazard, the benefit of routine xeromammography is qtuestionable when an efficient cytological service is available.
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