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Biomedical subjects

H G Kwa

Publications and source records attributed to H G Kwa.

At least 19 recordsLinked to original sources

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

The prognostic value of serum prolactin levels was assessed in a sequential series of 739 patients who were initially treated at Guy's Hospital, London, between 1975 and 1980. Prolactin was measured in 472 patients 1 day before (Hpr1) and in 457 patients 10 days after (Hpr2) mastectomy. Follow-up of the patients was up to August 1992 giving 6139 women-years with a median follow-up time of 11.5 years (13.7 for patients still living and 5.1 for those dead). The association between the three prolactin variables and reproductive and clinical factors was examined before assessing the prognostic value of prolactin levels in terms of overall, disease-specific and disease-free survival. Multivariate survival models were used in order to adjust for the effect of other prognostic variables. These were found to be: tumour size, degree of nodal involvement, tumour grade and age at diagnosis. The results showed that high Hpr2 or high postoperative increase in prolactin (i.e. Hpr2-Hpr1) were significantly related to shorter disease-specific survival (p = 0.04 and 0.01, respectively) in postmenopausal women. In addition there was some indication, which did not attain formal significance, for this association to occur for disease-free survival. Thus the rise in blood prolactin levels after surgery may be a weak indicator of poor prognosis of breast cancer in postmenopausal women.

Adult↗

Relationship of blood prolactin levels and the risk of subsequent breast cancer.

Between 1968 and 1976 a total of 5162 women volunteers were enrolled into a prospective study conducted on the Island of Guernsey. Up to February 1990 145 women subsequently developed breast cancer. Blood samples were taken at the time of enrollment and prolactin levels were known for 85% of the volunteers. In calculating the relationship between blood prolactin levels and subsequent breast cancer risk, women were excluded if they had a hysterectomy or an oophorectomy or had cancer at any site before enrollment. The final analysis was based on 2596 premenopausal and 1180 naturally postmenopausal women and, of these respectively, there were 71 and 40 volunteers who subsequently developed breast cancer. The total follow-up for these two groups was 49,941 and 22,360 woman-years, respectively. In assessing the relationship between blood prolactin levels and risk of subsequent breast cancer the cohort was divided into quintiles according to prolactin concentration and relative risks (RR) were estimated. In calculating these values possible confounding by age at entry, age at menarche, parity, age at first birth, years since menopause, body build, history of benign breast disease and family history of breast cancer were taken into consideration. There was no significant relation between risk of breast cancer and prolactin in either pre- or postmenopausal women. Hence prolactin appears not to be an important determinant of breast cancer risk.

Adolescent↗

The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women.

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.

Age Factors↗

Urinary epidermal growth factor excretion and breast cancer risk.

The amount of urinary epidermal growth factor (EGF) excreted was determined in 350 normal women of whom 37 subsequently developed breast cancer. These were a group of women selected on a case-control basis from 5000 volunteers who had participated in a prospective epidemiological study. Urinary EGF excretion was not correlated with known risk factors such as age at menarche or menopause, age at first or last full-term child or parity. Neither was it associated with day or length of menstrual cycle, breast mammographic parenchymal pattern or the blood concentration of prolactin, dehydroepiandrosterone or its sulphate ester. Univariate analysis indicated that the amount of urinary EGF was significantly correlated with urinary creatinine (P less than 0.001), age (P less than 0.001), urinary androsterone (P less than 0.02) or aetiocholanolone (P less than 0.02), height (P less than 0.05) and weight (P less than 0.05). However, multivariate analysis showed that the amount of urinary EGF was correlated only with creatinine excretion (P less than 0.001) and age (P less than 0.001) and that the significance of the other correlations were probably due to the confounding influence of creatinine.

Adult↗

The relationship between blood prolactin levels and risk of breast cancer in premenopausal women.

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.

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↗

Diurnal variations in prolactin and growth hormone levels in normal premenopausal vegetarian and omnivorous women.

Diurnal levels of plasma prolactin and growth hormone were measured in 47 normal premenopausal women, 26 of whom were established vegetarians and 21 of whom were omnivorous controls. There were no differences between the median prolactin levels of the two groups during a 24-hour period of investigation. When the groups were further subdivided into ovolactovegetarians and vegans, still no differences were found in prolactin secretion. In contrast, the vegetarian women exhibited elevation of growth hormone levels during the period of study, which was particularly marked at midnight and 10 A.M.

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↗

Effect of prednisolone on hormone profiles during primary endocrine treatment of advanced breast cancer.

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.

Breast Neoplasms↗

Plasma prolactin levels and breast cancer: relation to parity, weight and height, and age at first birth.

Plasma prolactin has been measured in over 3,500 women volunteers from a normal population. In premenopausal women there was a significant decrease in prolactin levels with increasing parity. However, this effect was transitory since plasma prolactin concentration rose with increasing time after the birth of the last child. There were no significant differences in prolactin levels with respect to height and weight, although overweight compared to underweight women had approximately 15% more plasma prolactin. If prolactin is a carcinogen, then these results are in keeping with the epidemiological findings that multiparity affords protection and that age at last delivery is a risk factor in the development of breast cancer.

Adult↗

A prospective study of plasma prolactin levels and subsequent risk of breast cancer.

Plasma prolactin was measured in 2,572 pre-menopausal, 628 menopausal, and 1,666 peri- and post-menopausal women who were apparently healthy. Breast cancer was subsequently diagnosed in 47 of these women at a median time of 5 years after blood collection (pre-cancer cases). Prolactin levels in pre-menopausal cases increased significantly with age whereas this was not found in matched controls. The perimenopausal cases were characterized by extreme variability in prolactin levels. In post-menopausal women who developed breast cancer, the prolactin levels were significantly elevated, being at or above the 70th percentile for the controls. In this group the results are consistent with prolactin acting as a late-stage tumour promoter.

Adult↗

Plasma prolactin levels in women at postmenopausal age with a family history of breast cancer or a prescription for antihypertensive Rauwolfia treatment.

An investigation was made of daytime plasma prolactin levels in three groups of women aged 50 to 64 years: (1) 139 women with a family history of breast cancer; (2) 50 women on Rauwolfia treatment for hypertension, and (3) 90 women of a control group. A significant difference in prolactin levels was found between groups 2 and 3 but not between 1 and 3. These findings are considered in relation to the results of a breast cancer screening programme in which the women took part. Here, it was the women with a family history of breast cancer who showed an increased breast cancer risk, whereas the risk in women on Rauwolfia was not significantly higher than expected on the basis of the experience among controls. It is concluded that the role of prolactin in the etiology of breast cancer is still not clear.

Breast Neoplasms↗

Abnormalities in evening plasma prolactin levels in nulliparous women with benign or malignant breast disease.

In the present study the assay results of prolactin concentrations in serial samples of blood obtained from premenopausal women with benign or malignant disease of the breast are compared with--and discussed in relation to--findings reported in earlier studies based on single samples of blood taken at various times from a large and ostensibly normal population of women. The finding of an abnormality in nycthemeral prolactin levels in the established disease is considered to strengthen the concept that the same abnormality found in high-risk groups is of aetiological importance.

Adenofibroma↗

An abnormal early evening peak of plasma prolactin in nulliparous and obese post-menopausal women.

Plasma specimens were obtained in the afternoon (13.30 to 17.29 h) from 668 post-menopausal women and in the evening (17.30 to 20.30 h) from 219 further women. The mean evening plasma prolactin level was significantly higher than that found in the afternoon (p less than 0.0007). Mean afternoon prolactin levels were not related to nulliparity and body weight. In nulliparous obese women the mean of the evening peak prolactin concentrations was double that of comparable women studied in the afternoon (p less than 0.003).

Circadian Rhythm↗

Value of luteinizing hormone-releasing hormone testing in bromocriptine treatment of amenorrhea and hyperprolactinemia in patients with pituitary tumors.

The results of bromocriptine treatment in 13 patients with radiologically evident pituitary tumors are described. A menorrhea was present in all patients, hyperprolactinemia in 12 of the 13 patients, and acromegaly in 3 patients. Five patients have previously been treated surgically and by radiotherapy because of suprasellar extension of the adenoma. Plasma prolactin levels after one single dose of 2.5 mg of bromocriptine were found to have no predictive value as to the dosage needed for treatment, whereas the plasma gonadotropin response after the administration of luteinizing hormone-releasing hormone appeared to be predictive with respect to the return of ovulation during bromocriptine therapy.

Adenoma↗