Estrogens in the causation of breast, endometrial and ovarian cancers — evidence and hypotheses from epidemiological findings

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Abstract

Estrogens along with progesterone/progestins, and other hormones, are important determinants of cancer in the breast, endometrium and ovary. Estrogens may increase the risk of breast cancer through various mechanisms and at various phases of life, with a possible synergistic effect of progesterone/progestins. Exposure to high doses of placental hormones, such as estrogens and/or progesterone, during pregnancy may play a pivotal role in reducing subsequent breast cancer susceptibility. Estrogens cause endometrial cancer, an effect that can be reduced, prevented or reversed by progesterone/progestin — if allowed to act for a sufficiently long period of each cycle. The role of sex hormones seems important for ovarian carcinogenesis. Intake of combined oral contraceptives has a substantial and well-documented protective effect on endometrial and ovarian cancer risks. Epidemiological observations and experimental data from an animal model indicate that estrogens may have an adverse effect, while progesterone/progestins have a risk reducing effect directly on the ovarian epithelium. Thus, estrogens and other sex hormones have potential effects on the three most important female cancers. Research has yet to define how some of the risk factors can be modified or treatment regimens can be improved to reduce these cancer risks.

Introduction

The exposure to estrogens during different phases of a woman's life can influence the risk of cancer in the main target organs, i.e. the breast, endometrium and ovary. Numerous epidemiological studies report associations between markers of ovarian or placental hormone production and cancer risks. In recent decades, also exogenous hormones — as in oral contraceptives and hormone replacement therapy — have been implicated as risk factors for cancer and also as preventive agents. Epidemiological observations give important clues as to the carcinogenetic role of sex hormones, but need support from clinical and basic research in order to verify and characterize their action in relevant pathways.

This presentation highlights some of the more recent epidemiological findings and their implications for research and for clinical practice.

Section snippets

Breast cancer

Breast cancer is the most frequent cancer among women world-wide, with approxinately a 5-fold higher incidence in some western countries as compared with Asian countries [1]. The cumulative incidence up to 74 years of age is as high as 7–9% in North America and other northern European countries [2]. The incidence has been rising in both developed and developing countries [3], whereas mortality in high-risk countries has been rather stable during past decades [4]. Migration studies reveal

Endometrial cancer

World-wide, endometrial cancer is the sixth most common cancer, accounting for about 2% of all incident cases in women. The incidence varies greatly between countries, being the highest in the USA and Northern Europe [35]. It generally has a favourable clinical course, the 5-year average survival being about 75% [3].

It is established that estrogens cause endometrial cancer. The key mechanism of carcinogenesis is an enhanced and long-standing proliferation of endometrial cells leading to a

Ovarian cancer

Globally, ovarian cancer is the fifth most common cancer among women. Incidence rates are the highest in Scandinavia, with intermediate rates in the USA and with the lowest, but increasing, rates in Japan [51]. Since most of the invasive cancers are diagnosed at an advanced stage, the prognosis is poor, with an average 5-year survival of less than 40% [51]. The non-invasive, borderline subtype, comprising about 20%t of all tumours, is associated with a considerably better prognosis.

References (67)

  • D.W. Cramer et al.

    Epidemiologic evidence for uterine growth factors in the pathogenesis of ovarian cancer

    Ann. Epidemiol.

    (1995)
  • H.O. Adami et al.

    Parity; age at first childbirth; and risk of ovarian cancer

    Lancet

    (1994)
  • B.J. Mosgaard et al.

    Infertility; fertility drugs; and invasive ovarian cancer: a case-control study

    Fertil. Steril.

    (1997)
  • P.P. Garg et al.

    Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis

    Obstet. Gynecol.

    (1998)
  • H.A. Risch

    Estrogen replacement therapy and risk of epithelial ovarian cancer

    Gynecol. Oncol.

    (1996)
  • A. Venn et al.

    Breast and ovarian cancer incidence after infertility and in vitro fertilisation

    Lancet

    (1995)
  • J. Waterhouse et al.

    Cancer incidence in five continents

    IARC Sci. Publ.

    (1992)
  • L. Tomatis, Cancer: causes. occurrence and control. IARC Sci. Publ. 100...
  • M.P. Coleman, J. Esteve, P. Damiecki, A. Arslan, H. Renard, Trends in cancer incidence and mortality. IARC Sci. Publ....
  • L. Lipworth

    Epidemiology of breast cancer

    Eur. J. Cancer Prev.

    (1995)
  • H. Yu et al.

    Comparative epidemiology of cancers of the colon; rectum; prostate and breast in Shanghai; China versus the United States

    Int. J. Epidemiol.

    (1991)
  • J.L. Kelsey

    A review of the epidemiology of human breast cancer

    Epidemiol. Rev.

    (1979)
  • B.S. Hulka et al.

    Steroid hormones and risk of breast cancer

    Cancer

    (1994)
  • M. Sanderson et al.

    Perinatal factors and risk of breast cancer

    Epidemiology

    (1996)
  • A. Ekbom et al.

    Perinatal characteristics and adult mammographic patterns

    Int. J. Cancer

    (1995)
  • M.C. Pike et al.

    ‘Hormonal’ risk factors; ‘breast tissue age’ and the age-incidence of breast cancer

    Nature

    (1983)
  • M. Lambe et al.

    Transient increase in the risk of breast cancer after giving birth

    N. Engl. J. Med.

    (1994)
  • C. Magnusson et al.

    Body size in different periods of life and breast cancer risk in post-menopausal women

    Int. J. Cancer

    (1998)
  • S.E. Hankinson et al.

    Alcohol; height; and adiposity in relation to estrogen and prolactin levels in postmenopausal women

    J. Natl. Cancer Inst.

    (1995)
  • E. Petridou et al.

    Determinants of age at menarche as early life predictors of breast cancer risk

    Int. J. Cancer

    (1996)
  • M.M. Kramer et al.

    Does physical activity reduce risk of estrogen-dependent cancer in women?

    Med. Sci. Sports Exerc.

    (1996)
  • D.J. Hunter et al.

    Diet; body size; and breast cancer

    Epidemiol. Rev.

    (1993)
  • G.A. Colditz

    Relationship between estrogen levels; use of hormone replacement therapy; and breast cancer

    J. Natl. Cancer Inst.

    (1998)
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