Elsevier

European Journal of Cancer

Volume 39, Issue 12, August 2003, Pages 1738-1745
European Journal of Cancer

Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign

https://doi.org/10.1016/S0959-8049(02)00837-7Get rights and content

Abstract

It is thought that the risk of atypical hyperplasia (AH) increases with age, particularly among postmenopausal women. Three hypotheses were investigated to try to explain this phenomena: use of hormone replacement therapy (HRT), increased breast cancer screening and improvements in radiological quality. Data were collected from the Bouches du Rhône breast cancer screening programme database and from the pathological registry of all women operated on for breast diseases in the district. The AH incidence rate was studied using a Poisson regression analysis. The change in the profile of breast diseases was explored through studying changes in the proportion of AH among benign lesions and malignant diseases. The AH incidence rate significantly increased over time (13.6% per year). The proportion of AH among the benign diseases increased with time and was significantly higher for HRT users (Odds Ratio (OR)=2.05; 95% Confidence Interval (CI): 1.43–2.93). While AH decreased with age among HRT non-users, it increased among users as a proportion of both benign and malignant lesions. The AH incidence rate significantly increased among pre- and postmenopausal women. Our study suggests that this increase is partly explained by the incidental discovery of these lesions by mammography and partly by a real increase of the disease among HRT users.

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.

References (33)

  • K.C Young et al.

    Mammographic film density and detection of small breast cancers

    Clin. Radiol.

    (1994)
  • P Roger et al.

    Dissociated overexpression of cathepsin D and estrogen receptor alpha in preinvasive mammary tumors

    Hum. Pathol.

    (2000)
  • W.D Dupont et al.

    Risk factors for breast cancer in women with proliferative breast disease

    N. Engl. J. Med.

    (1985)
  • W.D Dupont et al.

    Breast cancer risk associated with proliferative breast disease and atypical hyperplasia

    Cancer

    (1993)
  • S.J London et al.

    A prospective study of benign breast disease and the risk of breast cancer

    JAMA

    (1992)
  • D.C Allred et al.

    Histological and biological evolution of human premalignant breast disease

    Endocr. Relat. Cancer

    (2001)
  • H Olsson et al.

    Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors

    Breast Cancer Res. Treat.

    (1996)
  • C.S Potten et al.

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

    Br. J. Cancer

    (1988)
  • L.J Hofseth et al.

    Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast

    J. Clin. Endocrinol. Metab.

    (1999)
  • M.C Pike et al.

    Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk

    Epidemiol. Rev.

    (1993)
  • S.A Fuqua et al.

    A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions

    Cancer Res

    (2000)
  • G Turpin

    [Role of hormone replacement therapy during menopause in the cardiovascular prevention]

    Ann. Cardiol. Angeiol. (Paris)

    (1994)
  • P Orcel

    Risk factors and prevention of postmenopausal osteoporosis

    Rev. Prat.

    (1995)
  • J Jacquemier et al.

    [Departmental compilation of histoprognostic data in senology. Apropos of campaign screening in Bouches-du-Rhone]

    Bull. Cancer

    (1992)
  • C Byrne et al.

    Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk

    Cancer

    (2000)
  • European recommendations for quality assurance in the setting of mammographic screening for breast cancer. Report of...
  • Cited by (15)

    • Atypical epithelial hyperplasia of the breast: Current state of knowledge and clinical practice

      2010, Journal de Gynecologie Obstetrique et Biologie de la Reproduction
    • Hormones, Breast Disorders, and Lactation

      2020, Endocrinology (Switzerland)
    • Premalignant disorders of the breast in pregnancy and lactation

      2020, Advances in Experimental Medicine and Biology
    View all citing articles on Scopus
    View full text