Long term effects of tamoxifen on blood lipid values in breast cancer.
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Biomedical subjects
Publications and source records attributed to P E Preece.
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The effects of fine needle aspiration on subsequent mammography were studied in a group of women who were referred with palpable breast lumps. Fifty-two women aged between 36 and 73 (median 53) years underwent mammography before and within 5 days of needle aspiration. Preaspiration and postaspiration mammograms were examined 'blind' by one radiologist. In ten cases, a difference was seen between the preaspiration and postaspiration films. In seven (aged 36-50 years) this was due to aspirated cysts. In three the differences were unexpected and were more significant, although the radiological diagnosis was not altered. If this proportion is extrapolated for a large number of patients then significant numbers of artifacts from fine needle aspiration might be seen on mammograms. It is possible that some might be interpreted falsely as malignant and some small cancers might be obscured. Women accepted mammography more readily before aspiration than after.
We have measured the levels of tamoxifen and three of its metabolites in the blood of patients receiving tamoxifen alone or combination therapy with tamoxifen and medroxyprogesterone acetate. Our results indicate that addition of the progestogen significantly alters the metabolism of tamoxifen over a six-month period. We suggest that the interaction between these drugs may involve additional sites (probably hepatic) besides the desired target tumour.
One hundred and thirteen women aged 70 years or more with locoregional breast cancer were treated with tamoxifen alone as primary treatment. They were followed for a minimum of 5 years. Complete response occurred in 38 women, partial response in 17, no change in 34 and progressive disease in 24. Where progressive disease occurred, or where patients relapsed after an initial response, the most suitable conventional therapy was given. The actuarial 5-year survival rate was 49.4 per cent for all patients and was much higher (92 per cent) in those showing an initial complete response. Seventy patients (61.9 per cent) were not controlled by tamoxifen alone to death or most recent follow-up. Tamoxifen provides an alternative treatment for operable breast cancer in older women in the short term and may be particularly suitable for those with concurrent disease or who are unwilling to undergo surgery. The low morbidity rate from tamoxifen must be balanced against the need to maintain close follow-up. In the medium to long term, sole primary treatment by tamoxifen delays more definitive therapy.
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Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone.
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A clinic specialising in breast disease has been surveyed over a decade. Detailed information has been collected on 3,500 women with benign breast disorders and 950 with breast cancer. Over this time, the demand for and utilisation of this facility has increased steadily. Over the ten years, there has been a trend for a higher proportion of breast cancers to be smaller in size and for fewer cancers to be locally advanced or metastatic at presentation. Critical appraisal of referral and consultation patterns indicates that the original aims of establishing this clinic have not been maintained. Paradoxically, this is a result of the success of the exercise. Measures which might lead to a higher proportion of patients with breast cancer being managed at the Breast Clinic rather than a General Surgical Outpatient Clinic are discussed.
The tumour marker CA 15-3 has been assayed in 130 patients with breast cancer and correlated with stage of their disease at presentation. The median value of CA 15-3 (43 kU/l) in 26 patients with stage IV disease was significantly higher than the median for 97 patients classified as stage I or II (17 kU/l). Values were elevated in 18 of 21 (86%) patients with bone metastases at presentation. For the 41 patients with stage I or II disease presenting with levels of CA 15-3 of greater than 20 kU/l, the disease-free interval and survival were significantly less than for 56 patients presenting with levels of less than 20 kU/l. CA 15-3 provides additional information to conventional staging tests for patients presenting with breast cancer and may also have a role as a prognostic indicator. This may be particularly useful in the selection of patients for neoadjuvant therapy.
A 10-year experience using ovarian ablation and prednisolone as adjuvant therapy for premenopausal patients with breast carcinoma, emphasizing tolerability and morbidity is reported. Thirty patients (15 aged less than 45 years, 15 aged greater than or equal to 45 years; range 28-54 years) underwent mastectomy/lumpectomy with axillary clearance (with or without local irradiation) followed by ovarian irradiation and prednisolone therapy (2.5 mg three times daily for 5 years). Patients were reviewed every 3 months for the first 3 years and every 6 months thereafter. Follow-up was between 1.5 and 10 years (median 5 years). Twenty-four patients are still alive. Three patients stopped therapy because of side-effects. There was a mean(s.e.m.) weight gain of 8.46(1.69) per cent on therapy. Nineteen patients have been weaned off prednisolone over a period of 0.5-7.5 months (median 2 months) and the median length of time off steroids is now 3 years (range 0.5-5 years). This regimen appears to be associated with an acceptable level of patient tolerability and a low chronic morbidity rate and should be considered as an alternative to adjuvant systemic cytotoxic therapy.
A double-blind crossover study giving 20 mg/day of medroxyprogesterone acetate during the luteal phase was carried out in 26 women with cyclical mastalgia. Symptomatic response to this progestogen supplementation or placebo was assessed objectively by clinical examination and subjectively by linear analogue scales and breast pain charts. No significant relief of pain or tenderness was found on placebo or active treatment, irrespective of treatment order, and breast nodularity was similarly unaltered. No evidence of progesterone deficiency or prolactin abnormality was found. Side-effects were incurred in 11 patients (five on placebo, five on active treatment and one while on both) and were mostly vague premenstrual symptoms. We conclude that the therapeutic response of medroxyprogesterone acetate in cyclical mastalgia is no better than placebo and that progestogen supplementation can no longer be recommended for routine use in the management of breast pain.
Aspirate from an argyrophil carcinoma ("carcinoid") of the breast showed malignant dispersed epithelial cells. With Diff-Quik, the cytoplasm was seen to be abundant, with prominent eosinophilic granularity. The nuclei were fairly uniform, round or oval, and eccentric and had a finely stippled chromatin pattern. On histology, the tumor appeared typical for argyrophil carcinoma, and staining with Grimelius for argyrophilic granules was positive. Membrane-bound neurosecretory granules were seen on electron microscopy.
Since 1970 fine-needle aspiration cytology for breast tumours has grown in popularity and is now routinely used in the initial diagnosis of palpable breast masses in the United States and other parts of the world. Fast staining methods of the aspirate enables reporting within 10 minutes of the aspirate being performed. Training and experience is important in obtaining satisfactory smears for diagnosis, and pitfalls are false-negative and false-positive findings, which may have dire consequences for the patient if cytological diagnosis is the final arbiter. Conditions such as benign mammary dysplasia and sclerosing adenosis are the most common sources of highly cellular smears and often show marked atypia, which makes distinction from carcinoma difficult. Also, atypical papillary formations present a diagnostic problem, and biopsy is indicated to exclude a papillary carcinoma. Fine-needle aspirations very seldom cause traumatic complications, and these are usually of a minor degree. Seeding along the needle track has occurred, but in most cases with a larger-caliber (18 s.e.g.) needle. Aspiration itself has been shown to have no effect on the survival rates in breast carcinoma. Contemporary reports show that around 90% of cases of breast cancer can be detected with confidence by means of this procedure. The reduction in scar formation facilitates future evaluation of the patient as scar tissue often interferes with the interpretation of mammograms. Cost effectiveness is evident in terms of decreased use of anaesthetics and operating time and a reduction in the use of frozen section histology by about 80%.(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship between proteinase-like peptidase activities and oestrogen receptor levels and status in breast cancer tissue homogenates from 61 patients with breast cancer has been evaluated. With Spearman's rank-order correlation analysis, significant positive correlations were observed between receptor levels and the activities of cathepsin-(B + L)-like, cathepsin-H-like, trypsin-like, plasminogen-activator-like and elastase-like peptidases. In addition, the activities of all but the latter enzyme were significantly higher in patients with receptor-rich tumours than in receptor-poor tumours, and this may have implications for future treatment regimens for patients with oestrogen-receptor-rich tumours. The findings reported are consistent with the suggestion that in breast cancer there may be an association between steroid receptors and proteolytic enzymes such that the release of these enzymes may be under hormonal control.
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We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.
Needle aspiration with immediate cytological reporting has been practised in a breast clinic for one year. Patients benefit by receiving immediately the provisional diagnosis and, when indicated, appointments for metastatic surveys. Close co-operation between surgeon and cytologist has resulted in increased skill in aspiration, better preparation of samples, and greater accuracy in interpretation of reports. Since 5% of clinically benign lesions have proved malignant, even on immediate reporting, we would recommend cytological examination of all breast lumps.
To test the traditional surgical view that pain in the breast is largely an expression of psychoneurosis, the Middelesex Hospital Questionnaire was given to 317 women with mastalgia and 170 controls with varicose veins. Their scores were compared with those of 173 women psychiatric outpatients tested by the designers of the questionnaire. The results were broadly similar in the mastalgia and varicose veins groups, and where there were significant differences women with varicose veins had a higher psychoneurotic score in each case. Within the mastalgia group no difference in scores was observed between patients with cyclical mastalgia and those with mastalgia due to periductal mastitis. Both groups of surgical outpatients had significantly lower scores in major traits than the psychiatric group, except for a small group of patients with breast pain who persistently failed to respond to treatment. Patients with mastalgia are therefore no more "neurotic" than those with varicose veins, and differ greatly from patients with recognized psychoneurosis. Most patients have a physiological or pathological basis for their breast pain, and they deserve an appropriate diagnostic and therapeutic approach.