Search

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.

Forty-one patients with malignant pleural effusions secondary to breast cancer were randomly allocated to treatment with either intracavitary talc or intracavitary tetracycline. Of 33 evaluable patients, radiological control was achieved in 11/12 (92%) of the talc group compared with 10/21 (48%) of the tetracycline group (P = 0.022). Intracavitary talc provides effective palliation of metastatic pleural effusions secondary to breast cancer.

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.

Four hundred and forty-seven women with operable (TNM stage I or II) breast cancer in whom oestrogen receptors (ER), progesterone receptors (PgR) or both receptors had been assayed were studied. Receptor status was independent of axillary nodal status, but infiltrating duct carcinomas that were ER-, PgR- or ER-PgR- were more likely to be anaplastic (P less than 0.001). Four hundred patients with follow-up and uniform treatment were analysed for post-operative disease-free interval (DFI) and survival. No significant difference in DFI existed between patients with ER+ and ER- tumours or PgR+ and PgR- tumours, although there was a trend for longer DFI for ER+ and PgR+. DFI was longer in patients with better-differentiated (grade 1 and 2) tumours than with anaplastic (grade 3) tumours. In patients with ER+ tumours, those with grade 1 and 2 tumours had a longer DFI than those with grade 3 tumours (P less than 0.005). Survival was significantly longer in patients with ER+ tumours compared to those with ER- tumours (P less than 0.001), but there was no such association between tumour PgR and survival. Survival of patients with ER+PgR+ tumours was significantly longer than those with ER-PgR- tumours (P less than 0.025) and, in patients with no evidence of axillary nodal involvement, significantly longer than those with ER+PgR- tumours. Survival in patients with nodal involvement was influenced by histological grade, being longer in those with grade 1 or 2 tumours compared to those with grade 3 tumours. For ER+ tumours, survival was longer in patients with grade 1 or 2 than with grade 3 tumours. These results suggest that steroid receptors significantly affect survival but not DFI. This effect is most closely related to ER content, with relatively little additional information accruing from analysis of PgR. Histological grade influences both DFI and survival, and analysis of both grade and ER content may give a more accurate indication of prognosis in operable breast cancer.

Patients with locally advanced carcinoma of the breast were randomized to receive either radiotherapy alone, radiotherapy + endocrine therapy, radiotherapy + chemotherapy or radiotherapy + endocrine therapy + chemotherapy. In 363 evaluable patients, time to first progression was delayed significantly by both endocrine treatment and chemotherapy, the greatest effect being achieved by the combination of endocrine treatment and chemotherapy. This effect was almost entirely due to a major effect of systemic treatment on time to loco-regional progression, for which the result is highly significant, rather than time to distant metastasis in which only a non-significant trend was observed. For survival, a trend was seen in favour of the combination of hormone treatment and chemotherapy, but this effect did not achieve statistical significance. This trial suggests that current endocrine and cytotoxic treatments are only of marginal value in improving the prognosis in locally advanced breast cancer.

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.

In each of two population-based studies conducted on the Island of Guernsey between 1967-1976 and 1977-1984, respectively, single specimens of blood were taken from over 5000 normal women. From these two studies there were 1173 and 946 postmenopausal women in whom blood prolactin was determined and multivariate analysis was used to establish the association between blood prolactin concentration and possible determinants of risk of breast cancer. Since prolactin levels were log-normally distributed these analyses were done on log-transformed data. The age at menarche or menopause, age at first or last childbirth, length of reproductive life (i.e. time from menarche to menopause) or post-menopausal life (i.e. time from menopause to time of blood sampling), contraceptive use and history of breast cancer were not significantly associated with blood prolactin concentration. Of significance were age, parity, time of blood sampling and assay drift. Ponderosity (Quetelet's Index) was positively associated with prolactin concentration and this was significant using a one-tail criterion. Women with a mammographic pattern designated DY by Wolfe had significantly higher prolactin levels than those with N1 patterns. However, the main finding to emerge was that after standardizing for all the other variables increasing parity was related to a step-wise reduction in blood prolactin levels. Since this had occurred in women who had had their last child up to 35 years previously it implies this effect is permanent. It could therefore be that the protective effect on breast cancer risk of multiparity and early first pregnancy could be mediated by such a life-long reduction in blood prolactin levels.

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.

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.

One hundred and twenty-four patients with stage III breast cancer who had oestrogen receptor analyses (ER) performed on primary tumour were studied. For operable disease (T3a, N0.1, M0), patients with ER-negative (ER less than 5 fmol/mg cytosol protein) tumours had a shorter duration of symptoms, but no other differences were observed at presentation. In patients with inoperable (T3b,4, N0.1, M0 or any T, N2.3, M0) tumours there were no differences in the clinical characteristics that rendered the primary tumour inoperable between those with ER+ or ER- tumours. The median disease-free interval (DFI) in patients with operable tumours and uninvolved axillary nodes was significantly longer in those with ER+ tumours (P less than 0.05). Median survival was significantly longer in patients with ER+ tumours than in those with ER- tumours (50 vs 27.5 months, P less than 0.05), and when survival was analysed according to various methods of initial treatment, it was significantly prolonged in patients with operable (T3a, N0.1, M0) ER+ tumours compared to those with operable ER- tumours. In patients with inoperable tumours no effect of ER status on prognosis was demonstrated. These results suggest that oestrogen receptor content may be a prognostic variable in patients with operable stage III breast cancer, but further studies of patients with similar methods of initial treatment are needed to confirm this. Patients with operable stage III tumours should be considered separately from those with locally advanced inoperable tumours in view of the significant differences in their survival prospects.

Single specimens of blood have been taken from over 5000 normal volunteer women in each of two sequential (1967-1976, 1977-1984) population-based studied on the Island of Guernsey. Multivariate analysis was used to determine the relationship between prolactin levels and risk factors in breast cancer in 2591 and 1959 premenopausal women in whom blood prolactin had been measured. In both populations the prolactin concentrations appeared to be log-normally distributed and therefore all analyses have been done on log-transformed data. Initially the variables in the statistical model were age at menarche, ages at first and last baby, parity, ponderosity (Quetelet Index), mammographic pattern (as graded by Wolfe), family history of breast cancer, age, menstrual cycle status, time of day of blood sampling, oral contraceptive use, history of breast feeding and methodological changes in the laboratory measurement of prolactin. Of these variables age at menarche, ages at first and last child and family history of breast cancer were found not to be significant and were excluded from the final model. The main finding to emerge was that after standardizing for all the other variables, prolactin levels in the follicular phase were significantly lower than those found at midcycle or during the luteal phase of the menstrual cycle. A peak level of prolactin was found at day 12 of the cycle. Increasing parity was related to a steady decrease in prolactin concentration. Increasing ponderosity was associated with an increased prolactin level as was a DY compared to an N1 mammographic pattern. Women with a history of oral contraceptive use had lowered prolactin concentration. All these effects occurred evenly over the menstrual cycle and were generally found for both data sets. Thus body weight, parity and, indirectly, age at first baby might influence breast cancer risk by being associated with changes in blood prolactin concentration.

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.

Two hundred and four patients with progressive locally advanced or metastatic breast cancer not controllable by local therapy alone, and who had had no prior systemic therapy for advanced disease, were treated by primary endocrine therapy according to menopausal status. Premenopausal patients received ovarian irradiation (O) whilst postmenopausal patients received tamoxifen 10 mg b.d. (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg b.d. (P). In 180 evaluable patients, T + P induced significantly more responses than T alone (26/73 vs 9/72, P less than 0.01) and the addition of P to O in premenopausal patients also induced more responses than O alone (7/16 vs 4/19), but this difference was not significant and accrual of premenopausal patients continues. There was a trend for patients receiving T + P to have a longer survival than those receiving T alone (median 25 vs 16 months). These trends occurred in patients with tumours positive for oestrogen receptors and when receptor status was unknown; patients with receptor-negative tumours had a negligible response to endocrine treatment. P mitigated the occurrence of hypercalcaemia and tumour flare sometimes seen with T alone.