Biomedical subjects
Publications and source records attributed to R D Bulbrook.
Earlier studies of the serum concentration of progesterone during the luteal phase in women with benign breast disease have produced conflicting results. Serum progesterone profiles were therefore measured in relation to cyclical breast pain and in biopsied benign disease. No evidence of progesterone deficiency was found.
Serum profiles of both oestradiol and prolactin were measured during the luteal phase in normal women, in women with cyclical breast pain and in women with recently biopsied benign breast disease. The results suggest that, in women with benign breast disease, the concentration of both hormones may be increased, when compared to the normal controls, during the evening in the latter part of the luteal phase.
In a prospective study of 5,004 women in Guernsey, plasma samples were collected and stored. Retinol, beta-carotene and vitamin E levels were later measured in the samples from 39 women who subsequently developed breast cancer and from 78 controls who did not develop cancer. Plasma retinol levels were not related to the risk of breast cancer, mean levels among cases and controls being 485 micrograms l-1 and 479 micrograms l-1 respectively. Plasma vitamin E levels showed a clear association, low levels being associated with a significantly higher risk of cancer. The mean vitamin E levels among cases and controls were 4.7 mg l-1 and 6.0 mg l-1 respectively (P less than 0.025), and the risk of breast cancer in women with vitamin E levels in the lowest quintile was about 5-times higher than the risk for women with levels in the highest quintile (P less than 0.01). beta-carotene levels showed a tendency to be lower in women who developed cancer than in controls (36 micrograms l-1 among cases compared with 50 micrograms l-1 among controls) but the difference was not statistically significant.
Various plasma hormones were measured in 13 pre- and 20 post-menopausal women with advanced breast cancer before and for 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice a day, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day. These patients were taken from a larger clinical trial which demonstrated a higher response to primary endocrine therapy when prednisolone was added. Levels of dehydropiandrosterone sulfate were depressed in patients receiving prednisolone, confirming adrenal suppression. Estradiol levels were reduced in all patients, while luteinizing hormone and follicular stimulating hormone increased after ovarian irradiation, but all three hormones fell during tamoxifen administration; no further changes were caused by the addition of prednisolone. Prolactin and thyroxine remained constant throughout the study. There were no differences between responders and nonresponders in hormone profiles or in changes in the profiles after treatment.
Explore the source record for details and available documents.
The three major urinary androgen metabolites, dehydroepiandrosterone (DHEA), androsterone (ANDRO), and aetiocholanolone (AETIO) were measured in 1,484 volunteer women between 29 and 60 years of age on the island of Guernsey from 1962-1967. Twelve of these women subsequently developed ovarian cancer after a median interval of 130 months and a minimum interval of 19 months. All three androgen levels in these women were lower than those in controls matched for age and menopausal status. The results were most striking for DHEA, where half of the cases were below the 27th percentile of their matched controls (p = 0.007, two-sided). The results for ANDRO were of marginal significance (p = 0.06), and those for AETIO were not significant (p = 0.33).
370 patients who had carcinoma of the breast with involved axillary lymph-nodes were randomised after total mastectomy and axillary clearance to receive either no additional treatment or melphalan 6 mg/m2 daily for 5 days every 6 weeks for sixteen cycles. There was a trend towards longer relapse-free survival (RFS) in patients treated with melphalan, but this was not significant either in the whole series or in sub-groups according to menopausal status or extent of nodal involvement. In patients receiving melphalan RFS was not significantly affected by either the occurrence of amenorrhoea or the dosage of melphalan received. Overall survival did not differ significantly between the two groups. The results of this trial suggest that there is no place for the use of melphalan as adjuvant therapy in the management of early breast cancer.
Histopathologic features of the primary tumor and axillary lymph nodes from 97 consecutive patients with breast cancer from Japan were compared with those from 164 patients from England. Between the two groups, there were statistically significant differences in the morphology of the primary tumors regarding nuclear grade and patterns of tumor infiltration. In axillary lymph nodes, sinus histiocytosis was much more common in Japanese cases than in British cases, and was related to a diminished frequency of axillary node metastases. Germinal centers were also more common in the nodes of Japanese patients and were similarly associated with diminished frequency of metastases.
Explore the source record for details and available documents.
Serum 'free thyroxine' was measured as a thyroid function index (TFI) in 238 women with early breast cancer and 107 normal controls. The mean TFI was significantly lower in the cases compared with controls. The TFI was not related to pathological stage but correlated with histological grade, with the highest values found in well-differentiated (grade I) and the lowest in anaplastic tumours (grade III). A similar result was obtained with the urinary and androsterone:aetiocholanolone (5 alpha:5 beta) ratio in that the ratio was significantly lower in patients with grade III than in those with grade I tumours. These results indicate that thyroid hormones may be involved in tumour cell differentiation. Patients with low 5 alpha/5 beta ratios had significantly faster recurrence rates than those with high ratios. A similar trend was found for the TFI. The TFI decreases after mastectomy and at 12 months after operation is still below the pre-operative basal level.
Mammograms were obtained from 44 women aged over 30 years with bilateral primary breast cancer, 60 women with unilateral breast cancer, matched for age and menopausal status with the bilateral cases, and 937 normal women, again all aged over 30 years. The mammograms were classified according to Wolfe's criteria. Both groups of cancer patients were found to have a significantly (p less than 0.05) greater proportion of pre-menopausal women with the DY type of breast parenchymal pattern compared with the normal pre-menopausal women. No association was found between the P2 mammographic pattern and breast cancer. The study failed to show any difference in the distribution of mammographic risk categories in women with bilateral disease and those with unilateral cancers only.
Normal Japanese women had significantly more of their blood 17 beta-estradiol (E2) bound to sex hormone-binding globulin (SHBG) (53%) than British women (30%) and conversely less bound to albumin. While the proportion of SHBG-bound E2 increased with SHBG capacity and while binding fell as weight increased, the differences between the races do not appear to be explicable in terms of SHBG capacity or weight. At a given SHBG capacity, the Japanese women had more E2 bound to the protein than the British women. Where weights in the 2 populations overlapped, the Japanese women still had more of their E2 bound to SHBG than did the British women. Our results suggested that the affinity of albumin for E2 is lower in Japanese women.
Antibodies reacting with the host protein p53 were found in the sera of patients with primary or secondary carcinoma of the breast. Fourteen out of the 155 sera from breast cancer patients tested were positive for anti-p53 antibodies (9%) and no positives were detected among 164 control sera from normal women tested. The locations of the first metastasis in patients with positive sera were unusual, with more lung metastases and fewer bone metastases than expected. The detection of anti-p53 antibodies indicates that p53 is altered in amount, type or presentation in breast tumors so that it becomes immunogenic.
Explore the source record for details and available documents.
In premenopausal women with breast cancer, total serum oestradiol (E2) concentrations are normal but nonprotein-bound E2 concentration are significantly raised. This is not due to low sex-hormone-binding-globulin (SHBG) binding capacities which are within the normal range and is unlikely to be due to the small but significant decrease in albumin concentrations. In post-menopausal patients, both total and non-protein-bound E2 are significantly raised: this may be explained partially by lower SHBG binding capacities. In patients and controls there is a highly significant correlation between non-protein-bound E2 and SHBG but, for a given SHBG binding capacity, the patients have more non-bound E2 than controls. It is concluded that the breast in women with breast cancer may be exposed to elevated levels of biologically active E2 although the reasons for this remain obscure.
A prospective study has been carried out to compare the response rates to endocrine therapy of Japanese and British women with breast cancer. Premenopausal women were treated by ovarian ablation, patients who were up to five years postmenopausal were prescribed androgen therapy and patients who were more than five years postmenopausal were treated with oestrogens. No differences in response rate, response time or survival could be detected in the three categories of patients. Significantly more Japanese patients presented with pulmonary metastases in the pre- and postmenopausal groups. In postmenopausal Japanese patients treated with oestrogens, those with pulmonary metastases survived significantly longer.
Androsterone and aetiocholanolone were measured in urine specimens obtained from 218 women with early breast cancer. Patients who excreted less than the median amount of these steroids had a significantly higher recurrence rate (P less than 0.005) than patients excreting more than the median value. The relationship between androgen excretion and recurrence is stronger in pre-menopausal women that in the post-menopausal group. The androgen assays are still associated with recurrence rates when patients are stratified by pathological stage, but no clear relationship was found with histological grade.
Serum sialyl transferase (SST) was measured in 49 female patients with advanced breast cancer and 60 female controls. The mean SST level was significantly raised in patients with advanced breast cancer. There was no correlation between specific sites, or numbers of sites of metastatic disease and SST levels. The patients with advanced breast cancer were all treated with chemotherapy; in 13/21 responders there was a significant fall in SST and in 2 responders a significant rise in SST. The 6 patients who died after one course of chemotherapy had a significantly higher mean SST than those surviving longer. SST appears to lack sufficient specificity to be of practical value as a marker of response in patients with breast cancer treated by chemotherapy, though constant measurement of changes in SST may be of use in monitoring drug response. Raised SST at the commencement of chemotherapy may signify poor prognosis.