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Biomedical subjects

J L Hayward

Publications and source records attributed to J L Hayward.

At least 55 records · Page 3Linked to original sources

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↗

In situ ductal carcinoma of the breast: implications of disease pattern and treatment.

Ninety-seven patients with in situ ductal carcinoma (DCIS) of the breast have been reviewed. The commonest presenting feature was a breast lump, and residual carcinoma was found in the mastectomy specimen in 63% of patients. Furthermore, 13 cases had evidence of infiltrating carcinoma when the mastectomy specimen was examined. Thus excision alone would have left residual in situ or infiltrating carcinoma in two-thirds of the cases. A wide excision, by removing local residual disease, would still have left multifocal disease in one-third of cases. Studies need to be conducted to determine whether conservative treatment of DCIS can yield results which are as good as those following total mastectomy.

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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.

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Survival following local skin recurrence after mastectomy.

Seventy-three patients with breast cancer, treated by radical mastectomy, who subsequently developed a local skin recurrence without clinical evidence of disseminated disease, have been reviewed. There were significant differences between the survival of patients with single and multiple recurrences. Only 10 per cent of those with multiple lesions survived 5 years, and none was alive at 10 years, whereas 42 per cent of those with single lesions survived 5 years and 22 per cent were alive and well at 10 years' postrecurrence. Adequate local treatment of a single skin nodule may enable a subset of patients to survive without subsequent development of breast cancer metastases.

Breast Neoplasms↗

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.

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Which patients are cured of breast cancer?

The clinical and pathological features of 51 patients who survived for more than 20 years after diagnosis of cancer of the breast were compared with those of 176 contemporaries who died within 20 years after diagnosis. Of those who survived, 18 (35%) had had pathologically affected axillary nodes compared with at least 86 (49%) of those who died. Also, 11 (21%) of the survivors had had small tumours compared with 10 (6%) of those who died. Pathological review of tumours in the survivors showed 40 (78%) to have been infiltrating ductal carcinomas, of which 13 (32%) were grade 3 lesions. These differences between the two groups were largely due to the prognostic value of these variables in the first five years after diagnosis. After a patient had survived five years the major prognostic variables were of little value in the prediction of which patients would be cured of breast cancer. Advanced age, which was of little prognostic value in the first five years after diagnosis, was of significant prognostic value in the longer term, partly due to the steep age gradient for mortality from other diseases. Nevertheless, seven of 19 deaths more than 20 years after first treatment were due to breast cancer. Late deaths from breast cancer may, however, have often been the result of metastases from second primaries rather than the late manifestation of micrometastases from the original primary carcinoma. Age, menstrual state, clinical stage, and axillary nodes being affected are thus of some prognostic value in cancer of the breast, but the present inadequacy of knowledge of the behaviour of the disease makes accurate prediction of which patients will be cured impossible.

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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.

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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↗

Urinary hydroxyproline and prognosis in human breast cancer.

The excretion of urinary hydroxyproline has been measured before mastectomy in 342 patients presenting with breast cancer for the first time to Guy's Hospital. The first 106 women were maintained on a gelatine-free diet whilst the remainder were on unrestricted diet. In both dietary groups hydroxyproline levels or the ratio of hydroxyproline to urinary creatinine were not related to pathological stage or histological grade. The time between initial presentation and subsequent bone metastases was negatively and significantly associated with hydroxyproline excretion (P less than 0.05) and the ratio of hydroxyproline to creatinine (P less than 0.01) in women on a gelatine-free diet. A similar, but not significant, trend was observed in patients on unrestricted diet. Although hydroxyproline excretion was related to the time to onset of bone metastases the amount of hydroxyproline excreted by these patients was not significantly different from patients who had recurrences at sites other than bone or patients who were disease-free up to 5 years after initial diagnosis. The conclusion is that hydroxyproline is of little value in the early detection of bone metastases.

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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.

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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↗