Br. J. Surg. Vol. 62 (1975) 806-809
Sex hormones in breast disease P. C. E N G L A N D , L. G . S K I N N E R , K . M . C O T T R E L L A N D R . A . S E L L W O O D * SUMMARY
Serum concentrations of oestradiol I7p andprogesterone were measured daily throughout one menstrual cycle in 32 normal women, 32 women with benign disease of the breast and 10 women with cancer of the breast. In normal women concentrations varied with age. Women with cysts had concentrations of oestradiol 178 which were significantly higher than normal. In women with cancer the concentrations of oestradiol 178 and progesterone were sign$cantly higher than normal, but the dijierence was very small and much larger numbers of patients need to be studied. Concentrations of oestradiol 178 and progesterone in postmenopausal women were consistently very low.
THErelationship between the ovary and disease of the breast has never been explained in terms of hormonal activity. Measurement of urinary metabolites of ovarian hormones has proved an unsatisfactory method of study (England et al., 1974), but recently it has become possible by means of radio-immunoassay to measure simply and accurately the concentrations of ovarian hormones in blood (Abraham et al., 1971 ; Cameron and Jones, 1972; Furr, 1973). In the present study we have measured the concentration of oestradiol 17,5?-one of the most powerful of the oestrogens-and progesterone in serum from normal women and compared these findings with those in women with benign or malignant disease of the breast. Methods Subjects Samples of blood were taken daily or as often as possible during at least one menstrual cycle as follows : 1. Thirty-two normal women with no history of breast disease; 11 subjects were aged 20-29 years, 10 aged 30-39 years and 11 aged 40-49 years. 2. Thirty-two women with benign disease of the breast. Nineteen had painful lumpy breasts and were considered on clinical grounds to have generalized fibro-adenosis; 6 were aged 20-29 years, 8 aged 30-39 years and 5 aged 4 M 9 years. The remaining 13 had had one or more cysts aspirated from one or both breasts. Of these, 5 were aged 30-39 years and 8 aged 40-49 years. 3. Ten women, aged 40-49 years, with cancer of the breast; all the samples were taken approximately 3 months after mastectomy. Multiple samples were also obtained from 25 normal postmenopausal women between 47 and 64 years (mean age 56 years) and from 25 postmenopausal 806
women with cancer of the breast aged 52-79 years (mean age 63 years). None of the subjects had a history of gynaecological disease or was taking any hormonal preparation. Collection of blood samples Peripheral venous blood (approx. 10 ml) was collected daily between 9 a.m. and 12 noon. The blood was allowed to clot and then centrifuged and the serum removed and stored at - 20 “C. Measurement of serum oestradioll7p and progesterone Radio-immunoassay of oestradiol 178 was carried out by the method described by Cameron and Jones (1972) and England et al. (1974), and the radioimmunoassay of progesterone was based on that described by Furr (1973). Expression of results The lengths of the cycles varied greatly so that a reference point other than the first day of the cycle was needed for comparative purposes. The day of the mid-cycle peak of oestradiol 178 was used as the reference point and designated as day 0. Preceding days were given negative numbers and the days following positive numbers. Owing to the difference in profiles of the two hormones the period from day - 11 to day - 4 was referred to as the follicular phase and that from day + 4 to day 12 as the luteal phase for oestradiol 178, but day - 12 to day 0 was referred to as the follicular phase and day 2 to day 16 as the luteal phase for progesterone. Groups were compared by the statistical method of paired comparison.
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Results Premenopausal women 1 . Normal women : a. Oestradiol 178: During the follicular phase (day - 11 to day -4) of the cycle the concentrations of oestradiol 17p were low (mean 35.3 ? 4.39 (s.e.m.) pg/ml), rose to a peak (day 0) at the time of ovulation (mean 92.9 k 12.7 pg/ml) and during the luteal phase (day 4 to day + 12) fell to a plateau (mean 67.3 k 1.47 pg/nil). In the luteal phase of the cycle the mean concentrations of oestradiol 17p in women in the fourth decade were significantly higher than those of women in the fifth (P
Sex hormones in breast disease P. C. E N G L A N D , L. G . S K I N N E R , K . M . C O T T R E L L A N D R . A . S E L L W O O D * SUMMARY
Serum concentrations of oestradiol I7p andprogesterone were measured daily throughout one menstrual cycle in 32 normal women, 32 women with benign disease of the breast and 10 women with cancer of the breast. In normal women concentrations varied with age. Women with cysts had concentrations of oestradiol 178 which were significantly higher than normal. In women with cancer the concentrations of oestradiol 178 and progesterone were sign$cantly higher than normal, but the dijierence was very small and much larger numbers of patients need to be studied. Concentrations of oestradiol 178 and progesterone in postmenopausal women were consistently very low.
THErelationship between the ovary and disease of the breast has never been explained in terms of hormonal activity. Measurement of urinary metabolites of ovarian hormones has proved an unsatisfactory method of study (England et al., 1974), but recently it has become possible by means of radio-immunoassay to measure simply and accurately the concentrations of ovarian hormones in blood (Abraham et al., 1971 ; Cameron and Jones, 1972; Furr, 1973). In the present study we have measured the concentration of oestradiol 17,5?-one of the most powerful of the oestrogens-and progesterone in serum from normal women and compared these findings with those in women with benign or malignant disease of the breast. Methods Subjects Samples of blood were taken daily or as often as possible during at least one menstrual cycle as follows : 1. Thirty-two normal women with no history of breast disease; 11 subjects were aged 20-29 years, 10 aged 30-39 years and 11 aged 40-49 years. 2. Thirty-two women with benign disease of the breast. Nineteen had painful lumpy breasts and were considered on clinical grounds to have generalized fibro-adenosis; 6 were aged 20-29 years, 8 aged 30-39 years and 5 aged 4 M 9 years. The remaining 13 had had one or more cysts aspirated from one or both breasts. Of these, 5 were aged 30-39 years and 8 aged 40-49 years. 3. Ten women, aged 40-49 years, with cancer of the breast; all the samples were taken approximately 3 months after mastectomy. Multiple samples were also obtained from 25 normal postmenopausal women between 47 and 64 years (mean age 56 years) and from 25 postmenopausal 806
women with cancer of the breast aged 52-79 years (mean age 63 years). None of the subjects had a history of gynaecological disease or was taking any hormonal preparation. Collection of blood samples Peripheral venous blood (approx. 10 ml) was collected daily between 9 a.m. and 12 noon. The blood was allowed to clot and then centrifuged and the serum removed and stored at - 20 “C. Measurement of serum oestradioll7p and progesterone Radio-immunoassay of oestradiol 178 was carried out by the method described by Cameron and Jones (1972) and England et al. (1974), and the radioimmunoassay of progesterone was based on that described by Furr (1973). Expression of results The lengths of the cycles varied greatly so that a reference point other than the first day of the cycle was needed for comparative purposes. The day of the mid-cycle peak of oestradiol 178 was used as the reference point and designated as day 0. Preceding days were given negative numbers and the days following positive numbers. Owing to the difference in profiles of the two hormones the period from day - 11 to day - 4 was referred to as the follicular phase and that from day + 4 to day 12 as the luteal phase for oestradiol 178, but day - 12 to day 0 was referred to as the follicular phase and day 2 to day 16 as the luteal phase for progesterone. Groups were compared by the statistical method of paired comparison.
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Results Premenopausal women 1 . Normal women : a. Oestradiol 178: During the follicular phase (day - 11 to day -4) of the cycle the concentrations of oestradiol 17p were low (mean 35.3 ? 4.39 (s.e.m.) pg/ml), rose to a peak (day 0) at the time of ovulation (mean 92.9 k 12.7 pg/ml) and during the luteal phase (day 4 to day + 12) fell to a plateau (mean 67.3 k 1.47 pg/nil). In the luteal phase of the cycle the mean concentrations of oestradiol 17p in women in the fourth decade were significantly higher than those of women in the fifth (P
