Gillian K Reeves Emily Banks Timothy Ja

The importance of endogenous hormones in the etiology of breast cancer is evident from the strong relationships between breast cancer risk and certain aspects of a woman's reproductive history, such as age at menarche, age at first birth, and age at menopause.1 More recently, the risk of developing breast cancer among post-menopausal women has also been shown to increase substantially with increasing levels of circulating estradiol,2 thus providing more direct evidence for the role of hormones in the development of the disease. The relationship between endogenous hormones and breast cancer risk leads naturally to the question of whether exogenous hormones, such as oral contraceptives and postmenopausal hormone therapy, might also have an effect on breast cancer risk.

Over 60 epidemiological studies worldwide have examined breast cancer risk in relation to either hormonal contraceptive use or post-menopausal hormone therapy. There have been collaborative reanalyses of data on breast cancer risk in relation to both hormonal contracep-tives3,4 and postmenopausal hormone therapy,5 which have incorporated data from the vast majority of these original studies. In addition, a de tailed review of the relationship between both these types of hormonal preparations and cancer has been compiled by the International Agency for Research on Cancer (IARC).6 The latter review includes details of many of the individual studies and summarizes the results of the main collaborative reanalyses. Three large randomized controlled trials of postmenopausal hormone therapy have also published results with respect to breast cancer and their findings have been reviewed recently.7 Other specific types of exogenous hormone that have been examined in relation to breast cancer risk include diethylstilbestrol, which was commonly used during pregnancy in the 1950s, and fertility-enhancing drugs, such as clomiphene citrate, which have been used since the late 1960s.8 However, the amount of data on breast cancer risk in relation to these latter two types of hormonal preparation is substantially less than that available for hormonal contraceptives and post-menopausal hormone therapy.

The aim of this chapter is to review the evidence pertaining to the association of breast cancer risk with use of hormonal contraceptives, postmenopausal hormone therapy, and other types of exogenous hormone. In presenting the evidence on breast cancer risk in relation to hormonal contraceptives and postmenopausal hormone therapy, we have drawn heavily on the results of the collaborative reanalyses and the review of randomized trials of postmenopausal hormone therapy, and the reader is referred to the original publications for details of the individual studies. To put the findings for each class of exogenous hormones into context, each section begins with a brief outline of patterns of use and ends with a summary of the possible explanations for the findings and their implications in terms of disease incidence.



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