Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign
Introduction
Atypical hyperplasia (AH) (atypical lobular and/or ductal hyperplasia) is a benign breast disease which has been reported as a high risk factor for breast cancer 1, 2, 3. In a retrospective cohort study, Dupont and Page [1] demonstrated that women with AH, aged less than 50 years, had a 4- to 5-fold increase in breast cancer risk compared with women of a similar age from the general population. A histological model of human breast cancer showed that AH naturally evolves to in situ carcinomas (CIS) then to invasive carcinomas and metastatic disease [4]. In premenopausal women, AH is influenced by sex hormones 5, 6, 7. In fact, oestrogens, mediated through the oestrogen receptors, play a central role in regulating the growth and differentiation of the normal breast by stimulating and regulating the progesterone receptors that itself mediates the mitogenic effects of progesterone [8]. In postmenopausal women, the proportion of oestrogen receptors is stable in the absence of hormone replacement therapy (HRT) [9]. It is thought that AH increases over time in postmenopausal women, but this has not yet been documented. Three factors may explain the changes in the pattern of the AH trend among postmenopausal women. Firstly, HRT has been widely prescribed to postmenopausal women in order to reduce the side-effects of menopause [10] and as a possible means of reducing the risk of osteoporosis and cardiovascular diseases [11]. Secondly, screening programmes for breast cancer have been extended in most of the French districts leading to increased incidental discovery of the disease. Finally, radiological quality has been improved in the 1990s.
The aim of this study was to quantify the AH incidence time trend in the Bouches du Rhône district and to examine the contribution of screening and HRT to the observed time change.
Section snippets
Subjects
We carried out a retrospective study based on two information sources. Firstly, the screening programme for breast cancer from the Bouches du Rhône district, called ARCADES (Association pour la Recherche et le DEpistage des CAncers du Sein), which started in 1990. The target population consisted of all women aged 50–69 years who are invited every 3 years to attend screening by single oblique view mammograms. Breast lesions detected at screening were followed-up at the co-ordinating centre, by
AH incidence rate
After an initial increase due to the diagnosis of prevalent cases, the incidence rate of total breast benign diseases (NP, PDWA and AH) decreased almost linearly between 1994 and 1999 (Fig. 1). The incidence rate of benign breast lesions varied from 230.67 per 100 000 person-years to 196.27 per 100 000 person-years between 1994 and 1999 (rate of change of −3.8% per year (−1.9 to −5.6%)) in women aged 40–69 years (Fig. 1). In contrast, the incidence rate of AH varied from 11.42 to 18.59 per
Discussion
To our knowledge, this retrospective study is the first one evaluating the AH incidence pattern over time among postmenopausal women.
The main result of our study is that, among 40–69 year old women, the AH incidence rate significantly increased over time (13.6% per year from 1994 to 1999) in the Bouches du Rhône district, while the other benign breast diseases steadily decreased. Moreover this increase was still present among postmenopausal women (15.4% per year from 1994 to 1999), and the rate
Conclusions
The study clearly demonstrated that the AH incidence rate increased between 1994 and 1999, while other benign breast diseases globally decreased. AH proportion among other benign breast diseases also increased over time in women aged 40–69 years and this was significantly higher among HRT users, leading to the conclusion that HRT use might increase the development of AH. These results occurred in the context of a lower participation of postmenopausal women in the organised screening programme
Acknowledgements
We are grateful to F. Morin for help with the manuscript and L. Remontet for the statistical approach. This work has been supported by ARCADES, Institut Paoli-Calmettes, Ligue Départementale des Bouches du Rhone contre le Cancer.
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