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Biomedical subjects

R D Bulbrook

Publications and source records attributed to R D Bulbrook.

At least 55 records · Page 3Linked to original sources

Thyroid function and the incidence of breast cancer in Hawaiian, British and Japanese women.

Serum-free thyroxine (FT4) concentrations are lower in Hawaiian and Hawaiian Caucasian women than in Hawaiian Japanese, Hawaiian Filipino, Hawaiian Chinese, and English and Japanese mainland women. There is a high inverse correlation between FT4 and risk of breast cancer in these ethnic groups. Thyroid-stimulating hormone (TSH) concentrations, which are inversely correlated with FT4, generally show the same relationship.

Adult↗

The prevention of breast cancer.

The case for treating women at high risk of breast cancer with the anti-oestrogen tamoxifen is presented. This is a logical extension of a screening programme and is scientifically based on the effectiveness of tamoxifen in established disease, the relation between free oestradiol (and other hormone-related factors) to the risk of breast cancer, and the lack of side-effects from tamoxifen treatment. Choice of a high-risk group is critical; a specific trial protocol is outlined.

Adult↗

Salivary oestradiol and progesterone levels in premenopausal women with breast cancer.

The concentrations of oestradiol and progesterone have been measured in salivary specimens collected daily over a complete menstrual cycle in 12 patients with operable breast cancer and 12 normal control volunteers. There was no significant difference (P greater than 0.05) for either hormone between these two groups. Both showed a mid-cycle rise in oestradiol levels followed by a smaller but sustained increase during the luteal phase. The progesterone concentration increased markedly during the luteal phase of the cycle. Total or non-protein bound oestradiol levels measured in blood samples from 19 normal women were both linearly correlated (P less than 0.001) with the concentration of oestradiol in matched saliva samples. The amount of free oestradiol in blood was about twice that found in saliva.

Adult↗

Serum prolactin levels in women with breast cancer and their relationship to survival.

Serum prolactin (HPr) has been measured in 459 patients 1 day before (HPr-1) and in 433 patients 10 days after (HPr-2) treatment. These came from an unselected sequence of 739 patients with operable breast cancer who had been referred to Guy's Hospital over a period of 5 yr. In addition HPr was measured in 100, or more, women at 3, 6 or 12 months after mastectomy. The median levels of either HPr-1 or HPr-2 were higher in pre-menopausal compared with postmenopausal patients (P = 0.03 and 0.06, respectively). Mastectomy was associated with increased serum HPr in both pre- and post-menopausal patients (P less than 0.001 in both cases). Average levels at 3 months, or after, were similar to those found before treatment. Nulliparous women had a higher median amount of HPr-1 than parous which was significant in premenopausal patients (P less than 0.008) whilst HPr-2 levels were not related to parity. Thus the rise in HPr associated with surgery was greater in parous than nulliparous women. Prolactin levels were not related to nodal status or tumour size. However, the amounts of HPR-2 were significantly greater in women with histological grade 3 tumours than those with grade 1 or 2. Standardising for either nodal status, tumour size or histological grade seven situations were found in which HPr-1 or HPr-2 levels were of prognostic significance. Although some of these significant associations could be fortuitous all shared a common feature that the least favourable prognosis was associated with the highest HPr levels.

Adult↗

A prospective study of mammographic parenchymal patterns and risk of breast cancer.

Breast parenchymal patterns have been assessed by the method of Wolfe in a prospective study in Guernsey. Women with P2 or DY grades had approximately four times the risk of developing breast cancer compared with those with N1 or P1 grades. Age, weight, parity and age at birth of first child are all related to the distribution of mammographic patterns. The combination of these variables with Wolfe grades may identify subsets of the population at very high risk.

Adult↗

Identification of women at high risk of breast cancer.

Prospective studies of risk factors for breast cancer have been carried out since 1961 on a normal population which now comprises some 15,000 women. Classical (anamnestic) factors such as ages at menarche, menopause, or at first child, post-menopausal weight and high parity are not strong determinants of risk. Measurements of various aspects of endocrine function are more successful in identifying women at risk, as is assessment of mammographic parenchymal patterns but, again, these variables are not effective enough to make an intervention strategy imperative. However, the combination of classical, endocrinological, and radiological factors appears to achieve this aim. A substantial sub-set of women who have a four-fold risk of breast cancer may be identifiable.

Adult↗

Influence of reproductive history on age at diagnosis of breast cancer and prognosis.

The effect on age at breast cancer diagnosis of age at menarche, age at first baby, parity and age at menopause has been determined for 739 unselected patients diagnosed between 1975 and 1980 as having operable breast cancer. Age at diagnosis was significantly and positively associated with ages at menarche, first baby and menopause. The average number of children significantly declined with increasing age at diagnosis. This was largely due to a change in the proportion of patients who were nulliparous (15% in women aged 41-50 years compared to about 30% in those over 60 years). A group of 1,989 normal women whose reproductive history was also collected between 1975 and 1980 showed similar trends between age and age at menarche, age at first baby and parity as the patients. Thus it appears that these reproductive parameters do not alter the time of onset of breast cancer but could be explained by temporal changes in reproductive patterns. There was no significant correlation between age at menopause and age at diagnosis for patients whose age at menopause was no more than 54 years and age at diagnosis no less than 55 years, respectively. It is therefore unlikely that age at menopause affects age at diagnosis. Postmenopausal patients with 3 or more children had a significantly shorter disease-free interval and lower survival rate than those with less children. None of the other parameters was associated with prognosis.

Adult↗

Family history and bilateral primary breast cancer.

The prevalence of a family history of breast cancer was established in 54 women with bilateral primary breast cancer and 208 women with unilateral disease. Women with bilateral disease had significantly greater prevalence of family history than women with unilateral breast cancer (P less than 0.01). Compared with the unilateral cancers, a significantly greater proportion of bilateral cancers had first degree affected relatives (P less than 0.05). Moreover the affected relatives of probands with bilateral disease showed a significantly higher prevalence of bilateral breast cancer compared with the relatives of women with unilateral disease (P = 0.04). The findings suggested that bilateral disease was a characteristic of familial breast cancer.

Adult↗

Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer.

327 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after total mastectomy and axillary clearance, to receive either no additional treatment or oral cyclophosphamide 80 mg/m2 on days 1-14, intravenous methotrexate 32 mg/m2 on days 1 and 8, and intravenous fluorouracil 480 mg/m2 on days 1 and 8 (CMF), which was repeated every 28 days for twelve cycles. There was a significantly longer relapse-free survival (RFS) in patients treated with CMF. A prolonged RFS was seen in premenopausal patients, those with 1-3 nodes involved, and those with 4 or more nodes involved, but a similar trend in postmenopausal patients failed to reach statistical significance. RFS was greater in patients with CMF-induced amenorrhoea than in controls and in treated patients whose primary tumour contained progesterone receptors. Dose of chemotherapy did not have a significant effect on RFS. Survival was not influenced by treatment.

Adult↗

Nyctohemeral changes in plasma prolactin levels and their relationship to breast cancer risk.

The amount of prolactin has been determined in serial blood samples taken over 24 h from 20 pre- and 9 postmenopausal women volunteers. All women had a large increase in prolactin at night (24.00 h-03.00 h). A much smaller rise in prolactin occurred in the evening (18.00 h-20.00 h) which was just significantly different (p less than 0.05) from levels found in the afternoon. Prolactin concentrations at any given time in the 29 women were linearly correlated with corresponding levels in either of the adjacent time intervals. This correlation was highly significant (p less than 0.001) throughout 24 h, implying that a woman with a relatively high (or low) blood prolactin in the afternoon would have a similarly high (or low) concentration in the evening or at night. Premenopausal women had higher amounts of prolactin than postmenopausal volunteers throughout the day. Parity was found to be inversely related to prolactin levels in pre- and postmenopausal women; this effect was especially marked in the night peak of prolactin. In postmenopausal women an average of 33 years had elapsed since the birth of the last child, which implies that childbirth has a life-long effect on reducing prolactin levels. Thus the protective effect of early child-bearing and multiparity against developing breast cancer could be at least partly explained by these effects on serum prolactin levels.

Breast Neoplasms↗

Bilateral primary breast cancer: a prospective study of disease incidence.

A prospective study was carried out, between January 1980 and March 1982, of all women who presented to the Breast Cancer Unit, Guy's Hospital, with a second primary breast cancer. The percentage of new simultaneous tumours detected clinically or by mammography was approximately 3 per cent. Routine mammographic screening of the contralateral breasts of patients with unilateral disease increased the rate of detection, fivefold, of simultaneous bilateral cancers. The incidence of nonsimultaneous bilateral disease was 7.6 second cancers per thousand patients at risk per year. The annual rate of occurrence of second primary cancers was a constant event and showed no trend either to increase or to decrease with follow-up. However, the risk of a nonsimultaneous second cancer was strongly correlated with age at first primary. Women who developed their first breast cancers under the age of 40 years had three times the risk of developing a second breast cancer compared with those who developed their first cancer after the age of 40. The risk of a second nonsimultaneous primary was 5.9 times that of the risk of occurrence of cancer in the first breast in the general female population.

Adult↗

Urinary androgen and 17-hydroxylated corticosteroid metabolites and their relation to recurrence rates in early breast cancer.

The amounts of urinary androsterone and etiocholanolone are highly correlated with recurrence rates in patients with early breast cancer after treatment by mastectomy. A more efficient means of predicting the clinical course of the disease is obtained by using a ratio of these compounds to the amounts of individual 17-hydroxycorticosteroids in the urine. For instance, the ratio of androsterone to alpha-cortolone is particularly effective in identifying women with a high rate of recurrence, and this is largely independent of pathological stage and tumor grade.

17-Hydroxycorticosteroids↗

Serum carcinoembryonic antigen in the diagnosis and prognosis of women with breast cancer.

Serum carcinoembryonic antigen (CEA) has been measured in 628 patients before and 577 patients after treatment for breast cancer. These came from an unselected sequence of 730 women, subsequently diagnosed as having stage I or II breast cancer, referred to Guy's Hospital over a period of nearly 5 yr. CEA was also measured in serum from 238 ostensibly healthy volunteers and 65 women with benign breast disease. CEA measurements were of no diagnostic value. There were more patients with breast cancer with values in excess of 10 ng/ml measured preoperatively (7%) or after mastectomy (5%) than in controls (3%), but the difference is of marginal significance. High levels of CEA were not consistently associated with pathological stage or histological grade. Mastectomy was not associated with any significant change in the distribution of CEA levels. Patients with stage II disease and pre-operative CEA levels over 10 ng/ml has a faster recurrence rate than those with levels of less than 2.5 ng/ml. High levels were also associated with reduced survival. However, such patients comprised about 5% of women presenting with early breast cancer, so that the use of CEA measurements for prognosis is of limited value.

Adolescent↗