Menopausal oestrogens and breast cancer risk: An expanded case-control study

Abstract

The relationship between menopausal oestrogen use and breast cancer risk has long been of interest, particularly given extensive evidence that endogenous hormones are involved in aetiology (Henderson et al., 1982) and that oestrogens can induce mammary neoplasms in experimental animals (IARC, 1979). Interest heightened when Hoover et al. (1976), in a retrospective cohort study of menopausal oestrogen users, showed that the risk of breast cancer increased with years since initial exposure, reaching a significant risk of 2.0 after 15 years. Subsequent case-control studies, however, yielded conflicting results (Jick et al., 1980;Ross et al., 1980;Hoover et al., 1981;Kelsey et al., 1981;Hulka et al., 1982;Hiatt et al., 1984;Kaufman et al., 1984;Nomura et al., 1986). Most failed to find evidence of any overall excess risk, although several indicated that long-term users might be adversely affected. A further complication was that hormone effects appeared to be modified by ovarian status, but various studies disagreed on which subgroups were at highest risk. The different subgroups included women with a natural menopause (Jick et al., 1980;Hulka et al., 1982), women whose ovaries were retained (Ross et al., 1980) and women having undergone a bilateral oophorectomy Hiatt et al., 1984). In addition, two large case-control studies (Kelsey et al., 1981;Kaufman et al., 1984) (Brinton et al., 1981). Although hormone use was not associated with any substantial overall risk, there was some hazard suggested among women who received hormones following bilateral oophorectomy, obliterating the protective effect normally associated with the operation. In this group, risk increased with years of oestrogen use, reaching risks of 2-3 for users of ten or more years.Higher risks were observed among oophorectomized women who used hormones in the presence of other risk factors, including nulliparity, family history of breast cancer, and benign breast disease.We subsequently had the opportunity to expand the original case-control study, concentrating on women whose breast cancer was detected during the latter years of the screening project. The extension of this study more than doubled our original sample size, enabling detailed evaluations of hypotheses raised by the initial investigation risks among hormone-susceptible subgroups, and relationships of hormone use to varying disease states. Subjects and methodsSubjects for this case-control study participated in the Breast Cancer Detection Demonstration Project (BCDDP), a multi-centre breast cancer screening program involving over 280,000 women at 29 widely dispersed centres. This program, jointly

Hormone replacement treatment and breast cancer risk: a cooperative Italian study

“…Although there was no significnt interaction between exogenous oestrogen use and age at dia is, there was some suggestion of higher risk in the elderly, which is consistent with the biological decine in endogenous hormones with age (Cauley et al, 1989;Brinton and Schairer, 1993), as well as with data from other case-control studies (Brinton et al, 1986;Wmgo et al, 1987;Palmer et al, 1991;Kaufman et al, 1991). Along a similar line of reasoning (Brinton and Schairer, 1993), the OR was somewhat (though not significantly) higher in women with surgical menopause than in those with natural menopause.…”

Detection of estrogen DNA-adducts in human breast tumor tissue and healthy tissue by combined nano LC-nano ES tandem mass spectrometry

“…In the tumor sample signals could be seen at a retention time of 42, 2, and 37.3 min, respectively. This corresponded exactly with the same retention time as the dA 3 and dG 4 reference adduct. Remarkebly, 4OHEN adducts were found in either tumorous or healthy tissue, but never in the both tissues at the same time.…”

“…In the United States, for instance, 30% of post-menopausal women use hormone eeplacement therapy (HRT) [1], e.g., Premarin. Studies in which the development of breast and endometrial cancer was associated with estrogen therapy [2][3][4][5][6] were supported by a more recent follow-up study in which it was demonstrated that post-menopausal women have an increased risk of breast cancer when using estrogens, especially in combination with progestin [7]. In animals, too, a relationship between the administration of estrogens and the development of cancer was shown [8].…”

A population-based cohort study of HRT use and breast cancer in southern Sweden

“…Some studies have suggested that the tumour biology of breast cancer associated with HRT use is favourable (Brinton et al, 1986;Magnusson et al, 1996;Holli et al, 1998;O'Connor et al, 1998) and that the prognosis is better than for other women diagnosed at a similar age (Jernström et al, 1999;Schairer et al, 1999). It has also been suggested that there is an increase in the incidence of lobular breast cancer but not of ductal breast carcinomas in the US and that this increase could be due to HRT use (Li et al, 2000a,b).…”