Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort.
BACKGROUND
Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors.


METHODS
Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects.


RESULTS
Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor.


CONCLUSIONS
Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
K
K
Tikk
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
D
D
Sookthai
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
T
T
Johnson
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France.
S
S
Rinaldi
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France.
I
I
Romieu
Danish Cancer Society Research Center, Copenhagen.
A
A
Tjønneland
Danish Cancer Society Research Center, Copenhagen.
A
A
Olsen
Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
K
K
Overvad
INSERM, Centre for Research in Epidemiology and Population Health [CESP], Nutrition, Hormones and Women's Health Team, Villejuif; University of Paris Sud, UMRS, Villejuif; IGR, Villejuif, France.
F
F
Clavel-Chapelon
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne; Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Australia.
L
L
Baglietto
Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany.
H
H
Boeing
Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens; Hellenic Health Foundation, Athens, Greece.
A
A
Trichopoulou
Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens; Department of Epidemiology, Harvard School of Public Health, Boston, USA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
P
P
Lagiou
Hellenic Health Foundation, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, USA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
D
D
Trichopoulos
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
D
D
Palli
Epidemiology and Prevention Unit, National Tumor Institute (IRCCS), Milano.
V
V
Pala
Cancer Registry and Histopathology Unit, 'Civic-M. P. Arezzo' Hospital ASP, Ragusa.
R
R
Tumino
Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Torino.
S
S
Rosso
Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
S
S
Panico
Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, Barcelona.
A
A
Agudo
Public Health Directorate, Asturias.
V
V
Menéndez
Granada Cancer Registry, Andalusian School of Public Health, Granada; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid.
M-J
MJ
Sánchez
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid; Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian.
P
P
Amiano
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid; Department of Epidemiology, Murcia Regional Health Authority, Murcia.
J M
JM
Huerta Castaño
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid; Navarre Public Health Institute, Pamplona, Spain.
E
E
Ardanaz
National Institute for Public Health and the Environment (RIVM), Bilthoven; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; School of Public Health, Imperial College, London, UK.
H B
HB
Bueno-de-Mesquita
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
E
E
Monninkhof
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
C
C
Onland-Moret
Department of Radiation Sciences, University of Umeå, Umeå.
A
A
Andersson
Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
M
M
Sund
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø; Department of Research, Cancer Registry of Norway, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Society of Public Health, Helsinki, Finland.
E
E
Weiderpass
School of Clinical Medicine, University of Cambridge, Cambridge.
K-T
KT
Khaw
Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
T J
TJ
Key
Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
R C
RC
Travis
School of Public Health, Imperial College, London, UK.
M J
MJ
Gunter
School of Public Health, Imperial College, London, UK.
E
E
Riboli
INSERM, Centre for Research in Epidemiology and Population Health [CESP], Nutrition, Hormones and Women's Health Team, Villejuif; University of Paris Sud, UMRS, Villejuif; IGR, Villejuif, France.
L
L
Dossus
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany. Electronic address: r.kaaks@dkfz.de.
R
R
Kaaks
D001943:Breast Neoplasms / Q000097:blood* / Q000209:etiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D017698:Postmenopause; D017697:Premenopause; D011388:Prolactin / Q000097:blood*; D012307:Risk Factors
D011388:Prolactin
breast cancer; estrogen receptor; hormone replacement therapy; progesterone receptor; prolactin levels; prospective cohort