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Life Style, Molecular Pathology, and Breast Cancer Risk

Borgquist, Signe LU (2008) In Lund University, faculty of Medicine Doctoral Dissertation Series 2008:7.
Abstract
The breast cancer diagnosis covers a wide range of tumours with different geno- and phenotypic characteristics. The diversity among studies on life-style factors and their impact on breast cancer risk might be clarified by recognizing breast cancer as a heterogeneous disease. A major aim of this thesis was to investigate the association between several life-style factors and subsequent breast cancer risk according to pathological- and tumour biological characteristics. Further, we examined two novel tumour markers with respect to their relation to established tumour characteristics, estrogen-related-life-style-factors, and/or response to endocrine breast cancer treatment. The thesis is predominantly based on breast cancer cases from the... (More)
The breast cancer diagnosis covers a wide range of tumours with different geno- and phenotypic characteristics. The diversity among studies on life-style factors and their impact on breast cancer risk might be clarified by recognizing breast cancer as a heterogeneous disease. A major aim of this thesis was to investigate the association between several life-style factors and subsequent breast cancer risk according to pathological- and tumour biological characteristics. Further, we examined two novel tumour markers with respect to their relation to established tumour characteristics, estrogen-related-life-style-factors, and/or response to endocrine breast cancer treatment. The thesis is predominantly based on breast cancer cases from the Malmö Diet and Cancer Study, a prospective cohort study including 17 035 women with baseline examinations performed 1991-1996. The study cohort was followed by record-linkage with national cancer registries and at the end of follow-up in 2004, 622 women had been diagnosed with breast cancer. Additionally, we used a consecutive cohort of 512 women diagnosed with breast cancer at the Malmö University Hospital 1988 and 1992. Immunohistochemical assessments of different tumour markers were performed using the tissue microarray (TMA) technique. Analyses of dietary habits and tumour characteristics revealed an association between low energy intakes and a more aggressive histopathological phenotype as well as over-expression of the cell cycle regulating protein, cyclin D1. A low fat intake showed similar associations to tumour characteristics. The use of combined (estrogen-progestin) hormone replacement therapy was associated with an increased risk of breast cancer, although with comparatively favourable prognostics factors, such as lobular type, low grade, low proliferation, negative/low cyclin D1 expression and maintained expression of the tumour suppressor gene, p27. In a similar way obesity was associated with an increased risk of less aggressive breast cancer characterised by lobular type, grade II, low proliferation, HER2 negativity, ERα+, PgR+, but negative ERβ expression. The enzyme HMG-CoA reductase was differentially expressed in breast cancer and high expression was associated with a smaller tumour size, low grade, low proliferation, and expression of ERα and ERβ, but not PgR. Estrogen-related factors, such as obesity and use of hormonal replacement, were associated with an increased risk of tumours with high expression of HMG-CoA reductase. The novel estrogen receptor, ERβ, was associated with expression of ERα and PgR, but not with other established prognostic factors, such as tumour size, grade, and lymph node metastases. Co-expression of both estrogen receptors indicated an improved response to endocrine therapy. (Less)
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author
supervisor
opponent
  • Professor Hall, Per, Per Hall, MD, PhD, Dept. Medical Epidemiology and Biostatistics
organization
publishing date
type
Thesis
publication status
published
subject
keywords
hormone receptors, Breast cancer, tissue microarray, histopathology, ERβ, tumour proliferation, cyclin D1, p27, HMG-CoA reductas, life style factors, diet, hormone replacement therapy, obesity, endocrine therapy
in
Lund University, faculty of Medicine Doctoral Dissertation Series
volume
2008:7
pages
137 pages
publisher
Pathology (Malmö)
defense location
The main Lecture Hall, Department of Patholgy, Malmö University Hospital
defense date
2008-02-08 09:00
ISSN
1652-8220
ISBN
978-91-85897-60-5
project
Molecular Pathology
language
English
LU publication?
yes
id
ee1db636-c84a-414a-b756-56733a736aae (old id 927217)
date added to LUP
2008-01-14 11:30:24
date last changed
2016-09-19 08:44:48
@phdthesis{ee1db636-c84a-414a-b756-56733a736aae,
  abstract     = {The breast cancer diagnosis covers a wide range of tumours with different geno- and phenotypic characteristics. The diversity among studies on life-style factors and their impact on breast cancer risk might be clarified by recognizing breast cancer as a heterogeneous disease. A major aim of this thesis was to investigate the association between several life-style factors and subsequent breast cancer risk according to pathological- and tumour biological characteristics. Further, we examined two novel tumour markers with respect to their relation to established tumour characteristics, estrogen-related-life-style-factors, and/or response to endocrine breast cancer treatment. The thesis is predominantly based on breast cancer cases from the Malmö Diet and Cancer Study, a prospective cohort study including 17 035 women with baseline examinations performed 1991-1996. The study cohort was followed by record-linkage with national cancer registries and at the end of follow-up in 2004, 622 women had been diagnosed with breast cancer. Additionally, we used a consecutive cohort of 512 women diagnosed with breast cancer at the Malmö University Hospital 1988 and 1992. Immunohistochemical assessments of different tumour markers were performed using the tissue microarray (TMA) technique. Analyses of dietary habits and tumour characteristics revealed an association between low energy intakes and a more aggressive histopathological phenotype as well as over-expression of the cell cycle regulating protein, cyclin D1. A low fat intake showed similar associations to tumour characteristics. The use of combined (estrogen-progestin) hormone replacement therapy was associated with an increased risk of breast cancer, although with comparatively favourable prognostics factors, such as lobular type, low grade, low proliferation, negative/low cyclin D1 expression and maintained expression of the tumour suppressor gene, p27. In a similar way obesity was associated with an increased risk of less aggressive breast cancer characterised by lobular type, grade II, low proliferation, HER2 negativity, ERα+, PgR+, but negative ERβ expression. The enzyme HMG-CoA reductase was differentially expressed in breast cancer and high expression was associated with a smaller tumour size, low grade, low proliferation, and expression of ERα and ERβ, but not PgR. Estrogen-related factors, such as obesity and use of hormonal replacement, were associated with an increased risk of tumours with high expression of HMG-CoA reductase. The novel estrogen receptor, ERβ, was associated with expression of ERα and PgR, but not with other established prognostic factors, such as tumour size, grade, and lymph node metastases. Co-expression of both estrogen receptors indicated an improved response to endocrine therapy.},
  author       = {Borgquist, Signe},
  isbn         = {978-91-85897-60-5},
  issn         = {1652-8220},
  keyword      = {hormone receptors,Breast cancer,tissue microarray,histopathology,ERβ,tumour proliferation,cyclin D1,p27,HMG-CoA reductas,life style factors,diet,hormone replacement therapy,obesity,endocrine therapy},
  language     = {eng},
  pages        = {137},
  publisher    = {Pathology (Malmö)},
  school       = {Lund University},
  series       = {Lund University, faculty of Medicine Doctoral Dissertation Series},
  title        = {Life Style, Molecular Pathology, and Breast Cancer Risk},
  volume       = {2008:7},
  year         = {2008},
}