The effect of age and menstrual cycle upon proliferative activity of the normal human breast

Abstract

3Pathology and 4Surgery, Christie and Withington Hospitals, Manchester M20 9BX, UK.Summary The aim of this study was to determine the proliferative activity within the epithelial cells of the normal human breast in 122 patients (6 reduction mammoplasties and 116 fibroadenoma excisions) in relation to age and the phase of the menstrual cycle. Thirty three of the patients were on oral contraceptives and 33 were parous.Thin tissue slices were incubated with tritiated thymidine and processed for autoradiography. Other samples were fixed directly and prepared for histology. The labelling, mitotic and apoptotic indices (LI, MI and Al) were determined and all illustrated considerable variability. The labelling indices are significantly (P<0.05) influenced by both patient age and stage during the menstrual cycle and ranged from 0-11.5%. Maximum LI values were obtained on the 20.8th day of the cycle. A square root transformation of the data was used to reduce the skewness of the data to a more normal distribution. The square root of the LI declined by 0.22 per decade. The mitotic data showed similar significant (P<0.05) correlations against age and day of cycle with a peak on the 21.5th day of the cycle, a decline by 0.072 per decade and a range from 0-0.6%. The data for apoptotic cells were less clearly influenced by the stage of the menstrual cycle but showed a significant (P<0.5) decline with age. The Al in parous patients was significantly higher than that in non-parous patients. There was no significant effect of oral contraceptives on any of the parameters measured when age and stage of cycle were taken into account. The considerable variability in the data could not be fully accounted for by either technical factors, the age of the patients, or the day of the cycle.We conclude that proliferation is negatively related to age and is influenced by the menstrual cycle but that additional as yet unknown factors must account for a large part of the variability seen in the data.Events which occur early in reproductive life, such as exposure to ionising radiation or an early menarche, are known to be related to the subsequent development of malignant neoplasms of the breast (Land et al., 1980, MacMahon et al., 1973. The breast may be susceptable during this period because of a high rate of cellular proliferation and because carcinogenic agents may act preferentially upon proliferating tissues (Russo et al., , 1987. However there are few data concerning the association between age and proliferative activity of the normal human breast (Anderson et al., 1982, Meyer, 1977Russo et al., 1987) and one aim of this study was to investigate this relationship further.Oestrogen is a major growth promoting hormone of the breast: under some circumstances progesterone acts as an antioestrogen and appears to inhibit proliferation (MauvaisJarvis et al., 1986). On the basis of these observations Korenman (1980) proposed that the risk of breast cancer was related to a defective luteal phase with low or absent progesterone secretion. Women w...

Epithelial proliferation and hormone receptor status in the normal post-menopausal breast and the effects of hormone replacement therapy

“…This also allow s comparison with many of the studies of premenopausal breast. which considered lobular epithelium only (Anderson et al 1982: Potten et al 1988: Williams et al 1991 Figure 1A) and found to be unrelated to patient age (within the range of 49-68 years) (n = Il1. rho = 0.002.…”

“…-stimulation and the lowered proliferation rates that we have demonstrated. It is well documented that age also exerts a significant negative effect upon proliferation in premenopausal (Meyer 1977: Anderson et al 1982: Potten et al 1988) and postmenopausal (Mever and Connor. 1982) breast epithelium.…”

“…although the evidence that serum oestradiol levels also decline is lacking (Meyer 1977: Anderson et al 1982: Potten et al 1988. sugestin2 that sensitivity of the breast to oestradiol attenuates with ace.…”

Steroid hormones and risk of breast cancer

“…The influence of sex steroid hormones and hormonally mediated factors on human breast tissue proliferative rates has been reported by Anderson et al 89 and Potten et al 90 Anderson et al used 3H-thymidine labeling and autoradiography on biopsy material from benign breast lesions. They observed higher labeling indexes from (1) younger versus older women (or women with recent versus remote menarche), (2) luteal versus follicular phase of the menstrual cycle, (3) users of oral contraceptives versus nonusers (primarily in nulliparous women), and (4) high estrogen dosage versus low dose oral contraceptive^.^^ Potten et al used similar methods and materials and obtained similar findings with respect to patient age and menstrual cycle phase.'"…”

The receptor tyrosine kinase Met and the protein tyrosinephosphatase PTPN2 in breast cancer

“…The lobules will develop more during the luteal phase, the second half of the cycle after ovulation, and more mitotic activity is seen. If no pregnancy occurs, these changes degenerate [3].…”