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Title: Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies
Authors: E. E. Calle
C. W. Heath
H. L. Miracle-McMahill
R. J. Coates
J. M. Liff
S. Franceschi
R. Talamini
N. Chantarakul
S. Koetsawang
D. RachawatRachawat
A. Morabia
L. Schuman
W. Stewart
M. Szklo
C. Bain
F. Schofield
V. Siskind
P. Band
A. J. Coldman
R. P. Gallagher
T. G. Hislop
P. Yang
S. W. Duffy
L. M. Kolonel
A. M.Y. Nomura
M. W. Oberle
H. W. Ory
H. B. Peterson
H. G. Wilson
P. A. Wingo
K. Ebeling
D. Kunde
P. Nishan
G. Colditz
N. Martin
T. Pardthaisong
S. Silpisornkosol
C. Theetranont
B. Boosiri
S. Chutivongse
P. Jimakorn
P. Virutamasen
C. Wongsrichanalai
A. J. McMichael
T. Rohan
M. Ewertz
C. Paul
D. C.G. Skegg
P. Boyle
M. Evstifeeva
J. R. Daling
K. Malone
E. A. Noonan
J. L. Stanford
D. B. Thomas
N. S. Weiss
E. White
N. Andrieu
A. Brêmond
F. Clavel
B. Gairard
J. Lansac
L. Piana
R. Renaud
S. R.P. Fine
H. R. Cuevas
P. Ontiveros
A. Palet
S. B. Salazar
N. Aristizabel
A. Cuadros
A. Bachelot
M. G. Lê
J. Deacon
J. Peto
C. N. Taylor
E. Alfandary
B. Modan
E. Ron
G. D. Friedman
R. A. Hiatt
T. Bishop
J. Kosmelj
M. Primic-Zakelj
B. Ravnihar
J. Stare
W. L. Beeson
G. Fraser
D. S. Allen
R. D. Bulbrook
J. Cuzick
I. S. Fentiman
J. L. Hayward
D. Y. Wang
R. L. Hanson
M. C. Leske
M. C. Mahoney
P. C. Nasca
A. O. Varma
A. L. Weinstein
American Cancer Society
Emory University
IRCCS Centro Di Riferimento Oncologico Aviano
Mahidol University
Johns Hopkins University
University of Queensland
British Colombia Cancer Agency
MRC Biostatistics Unit
University of Hawaii System
Centers for Disease Control and Prevention
Central Institute of Cancer Research
Brigham and Women's Hospital
Chiang Mai University
Chulalongkorn University
Food Science Australia
Kraeftens Bekaempelse
University of Otago
Istituto Europeo di Oncologia
Fred Hutchinson Cancer Research Center
Holly Lodge
Hospital General de Mexico
Hospital Universitario
Institut de Cancerologie Gustave Roussy
The Institute of Cancer Research, London
Israel Chaim Sheba Medical Center
Kaiser Permanente
Cancer Research UK
Onkoloski institut Ljubljana
Loma Linda University Adventist Health Sciences Center
Skånes universitetssjukhus
Maastricht University
University of the Philippines Manila
Istituto 'Mario Negri'
Divisione di Statistica Medica e Biometria
Istituto di Statistica Medica e Biometria
Nairobi Centre for Research in Reproduction
National Cancer Institute
National Institute of Child Health and Human Development
National University of Singapore
The Netherlands Cancer Institute
Columbia University Medical Center
Ontario Cancer Treatment and Research Foundation
Clinical Trial Service Unit
University of Costa Rica
Medical Center of Fudan University
Shanghai Institute of Planned Parenthood Research
Tianjin Cancer Institute and Hospital
Universitetet i Tromso
Universidad de Chile
University of Edinburgh
The University of North Carolina at Chapel Hill
University of Nottingham
University of Southern California
Uppsala Universitet
University of Wisconsin
Organisation Mondiale de la Sante
Keywords: Medicine
Issue Date: 22-Jun-1996
Citation: Lancet. Vol.347, No.9017 (1996), 1713-1727
Abstract: Background: The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. Methods: Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. Findings: The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95% Cl] in current users 1·24 [1·15-1·33], 2p<0·00001; 1-4 years after stopping 1·6 [1·08-1·23], 2p=0·00001; 5-9 years after stopping 1·07 [1·02-1·13], 2p=0·009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1·01 [0·96-1·05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives: for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0·88 (0·81-0·95; 2p=0·002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90% of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0·5 (95% Cl 0·3-0·7), 1·5 (0·7-2·3), and 4·7 (2·7-6·7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons. Interpretation: Women who are currently using combined oral contraceptives or have used them in the past 10 years are at a slightly increased risk of having breast cancer diagnosed, although the additional cancers diagnosed tend to be localised to the breast. There is no evidence of an increase in the risk of having breast cancer diagnosed 10 or more years after cessation of use, and the cancers diagnosed then are less advanced clinically than the cancers diagnosed in never-users.
ISSN: 01406736
Appears in Collections:Scopus 1991-2000

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