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

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. GallagherT. 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, Thomas E. 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, T. R. Moller, H. Olsson, J. Ranstam, R. A. Goldbohm, P. A. van den Brandt, R. A. Apelo, J. Baens, J. R. de la Cruz, B. Javier, L. B. Lacaya, C. A. Ngelangel, C. La Vecchia, E. Negri, E. Marubini, M. Ferraroni, M. Gerber, S. Richardson, C. Segala, D. Gatei, P. Kenya, A. Kungu, J. G. Mati, L. A. Brinton, R. Hoover, C. Schairer, R. Spirtas, H. P. Lee, M. A. Rookus, F. V. van Leeuwen, J. A. Schoenberg, M. D. Gammon, E. A. Clarke, L. Jones, K. McPherson, A. Neil, M. Vessey, D. Yeates, V. Beral, D. Bull, B. Crossley, C. Hermon, S. Jones, T. Key, C. Lewis, G. Reeves, P. Smith, R. Collins, R. Doll, R. Peto, P. Hannaford, C. Kay, L. Rosero-Bixby, Y. T. Gao, J. M. Yuan, H. Y. Wei, T. Yun, C. Zhiheng, G. Berry, J. Cooper Booth, T. Jelihovsky, R. MacLennan, R. Shearman, Q. S. Wang, C. J. Baines, A. B. Miller, C. Wall, E. Lund, H. Stalsberg, A. Dabancens, L. Martinez, R. Molina, O. Salas, F. E. Alexander, B. S. Hulka, C. E D Chilvers, L. Bernstein, R. W. Haile, A. Paganini-Hill, M. C. Pike, R. K. Ross, G. Ursin, M. C. Yu, H. O. Adami, R. Bergstrom, M. P. Longnecker, P. Newcomb, T. M N Farley, S. Holck, O. Meirik

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1713-1727
Number of pages15
JournalLancet
Volume347
Issue number9017
StatePublished - Jun 22 1996
Externally publishedYes

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Contraceptive Agents
Epidemiologic Studies
Breast Neoplasms
Contraceptives, Oral, Combined
Neoplasms
Breast
Hormones
Reproductive History
Oral Contraceptives
North America
Parity
Early Detection of Cancer
Ethnic Groups

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Calle, E. E., Heath, C. W., Miracle-McMahill, H. L., Coates, R. J., Liff, J. M., Franceschi, S., ... Meirik, O. (1996). 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. Lancet, 347(9017), 1713-1727.

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. / Calle, E. E.; Heath, C. W.; Miracle-McMahill, H. L.; Coates, R. J.; Liff, J. M.; Franceschi, S.; Talamini, R.; Chantarakul, N.; Koetsawang, S.; RachawatRachawat, D.; Morabia, A.; Schuman, L.; Stewart, W.; Szklo, M.; Bain, C.; Schofield, F.; Siskind, V.; Band, P.; Coldman, A. J.; Gallagher, R. P.; Hislop, T. G.; Yang, P.; Duffy, S. W.; Kolonel, L. M.; Nomura, A. M Y; Oberle, M. W.; Ory, H. W.; Peterson, H. B.; Wilson, H. G.; Wingo, P. A.; Ebeling, K.; Kunde, D.; Nishan, P.; Colditz, G.; Martin, N.; Pardthaisong, T.; Silpisornkosol, S.; Theetranont, C.; Boosiri, B.; Chutivongse, S.; Jimakorn, P.; Virutamasen, P.; Wongsrichanalai, C.; McMichael, A. J.; Rohan, Thomas E.; Ewertz, M.; Paul, C.; Skegg, D. C G; Boyle, P.; Evstifeeva, M.; Daling, J. R.; Malone, K.; Noonan, E. A.; Stanford, J. L.; Thomas, D. B.; Weiss, N. S.; White, E.; Andrieu, N.; Brêmond, A.; Clavel, F.; Gairard, B.; Lansac, J.; Piana, L.; Renaud, R.; Fine, S. R P; Cuevas, H. R.; Ontiveros, P.; Palet, A.; Salazar, S. B.; Aristizabel, N.; Cuadros, A.; Bachelot, A.; Lê, M. G.; Deacon, J.; Peto, J.; Taylor, C. N.; Alfandary, E.; Modan, B.; Ron, E.; Friedman, G. D.; Hiatt, R. A.; Bishop, T.; Kosmelj, J.; Primic-Zakelj, M.; Ravnihar, B.; Stare, J.; Beeson, W. L.; Fraser, G.; Allen, D. S.; Bulbrook, R. D.; Cuzick, J.; Fentiman, I. S.; Hayward, J. L.; Wang, D. Y.; Hanson, R. L.; Leske, M. C.; Mahoney, M. C.; Nasca, P. C.; Varma, A. O.; Weinstein, A. L.; Moller, T. R.; Olsson, H.; Ranstam, J.; Goldbohm, R. A.; van den Brandt, P. A.; Apelo, R. A.; Baens, J.; de la Cruz, J. R.; Javier, B.; Lacaya, L. B.; Ngelangel, C. A.; La Vecchia, C.; Negri, E.; Marubini, E.; Ferraroni, M.; Gerber, M.; Richardson, S.; Segala, C.; Gatei, D.; Kenya, P.; Kungu, A.; Mati, J. G.; Brinton, L. A.; Hoover, R.; Schairer, C.; Spirtas, R.; Lee, H. P.; Rookus, M. A.; van Leeuwen, F. V.; Schoenberg, J. A.; Gammon, M. D.; Clarke, E. A.; Jones, L.; McPherson, K.; Neil, A.; Vessey, M.; Yeates, D.; Beral, V.; Bull, D.; Crossley, B.; Hermon, C.; Jones, S.; Key, T.; Lewis, C.; Reeves, G.; Smith, P.; Collins, R.; Doll, R.; Peto, R.; Hannaford, P.; Kay, C.; Rosero-Bixby, L.; Gao, Y. T.; Yuan, J. M.; Wei, H. Y.; Yun, T.; Zhiheng, C.; Berry, G.; Cooper Booth, J.; Jelihovsky, T.; MacLennan, R.; Shearman, R.; Wang, Q. S.; Baines, C. J.; Miller, A. B.; Wall, C.; Lund, E.; Stalsberg, H.; Dabancens, A.; Martinez, L.; Molina, R.; Salas, O.; Alexander, F. E.; Hulka, B. S.; Chilvers, C. E D; Bernstein, L.; Haile, R. W.; Paganini-Hill, A.; Pike, M. C.; Ross, R. K.; Ursin, G.; Yu, M. C.; Adami, H. O.; Bergstrom, R.; Longnecker, M. P.; Newcomb, P.; Farley, T. M N; Holck, S.; Meirik, O.

In: Lancet, Vol. 347, No. 9017, 22.06.1996, p. 1713-1727.

Research output: Contribution to journalArticle

Calle, EE, Heath, CW, Miracle-McMahill, HL, Coates, RJ, Liff, JM, Franceschi, S, Talamini, R, Chantarakul, N, Koetsawang, S, RachawatRachawat, D, Morabia, A, Schuman, L, Stewart, W, Szklo, M, Bain, C, Schofield, F, Siskind, V, Band, P, Coldman, AJ, Gallagher, RP, Hislop, TG, Yang, P, Duffy, SW, Kolonel, LM, Nomura, AMY, Oberle, MW, Ory, HW, Peterson, HB, Wilson, HG, Wingo, PA, Ebeling, K, Kunde, D, Nishan, P, Colditz, G, Martin, N, Pardthaisong, T, Silpisornkosol, S, Theetranont, C, Boosiri, B, Chutivongse, S, Jimakorn, P, Virutamasen, P, Wongsrichanalai, C, McMichael, AJ, Rohan, TE, Ewertz, M, Paul, C, Skegg, DCG, Boyle, P, Evstifeeva, M, Daling, JR, Malone, K, Noonan, EA, Stanford, JL, Thomas, DB, Weiss, NS, White, E, Andrieu, N, Brêmond, A, Clavel, F, Gairard, B, Lansac, J, Piana, L, Renaud, R, Fine, SRP, Cuevas, HR, Ontiveros, P, Palet, A, Salazar, SB, Aristizabel, N, Cuadros, A, Bachelot, A, Lê, MG, Deacon, J, Peto, J, Taylor, CN, Alfandary, E, Modan, B, Ron, E, Friedman, GD, Hiatt, RA, Bishop, T, Kosmelj, J, Primic-Zakelj, M, Ravnihar, B, Stare, J, Beeson, WL, Fraser, G, Allen, DS, Bulbrook, RD, Cuzick, J, Fentiman, IS, Hayward, JL, Wang, DY, Hanson, RL, Leske, MC, Mahoney, MC, Nasca, PC, Varma, AO, Weinstein, AL, Moller, TR, Olsson, H, Ranstam, J, Goldbohm, RA, van den Brandt, PA, Apelo, RA, Baens, J, de la Cruz, JR, Javier, B, Lacaya, LB, Ngelangel, CA, La Vecchia, C, Negri, E, Marubini, E, Ferraroni, M, Gerber, M, Richardson, S, Segala, C, Gatei, D, Kenya, P, Kungu, A, Mati, JG, Brinton, LA, Hoover, R, Schairer, C, Spirtas, R, Lee, HP, Rookus, MA, van Leeuwen, FV, Schoenberg, JA, Gammon, MD, Clarke, EA, Jones, L, McPherson, K, Neil, A, Vessey, M, Yeates, D, Beral, V, Bull, D, Crossley, B, Hermon, C, Jones, S, Key, T, Lewis, C, Reeves, G, Smith, P, Collins, R, Doll, R, Peto, R, Hannaford, P, Kay, C, Rosero-Bixby, L, Gao, YT, Yuan, JM, Wei, HY, Yun, T, Zhiheng, C, Berry, G, Cooper Booth, J, Jelihovsky, T, MacLennan, R, Shearman, R, Wang, QS, Baines, CJ, Miller, AB, Wall, C, Lund, E, Stalsberg, H, Dabancens, A, Martinez, L, Molina, R, Salas, O, Alexander, FE, Hulka, BS, Chilvers, CED, Bernstein, L, Haile, RW, Paganini-Hill, A, Pike, MC, Ross, RK, Ursin, G, Yu, MC, Adami, HO, Bergstrom, R, Longnecker, MP, Newcomb, P, Farley, TMN, Holck, S & Meirik, O 1996, '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', Lancet, vol. 347, no. 9017, pp. 1713-1727.
Calle, E. E. ; Heath, C. W. ; Miracle-McMahill, H. L. ; Coates, R. J. ; Liff, J. M. ; Franceschi, S. ; Talamini, R. ; Chantarakul, N. ; Koetsawang, S. ; RachawatRachawat, D. ; Morabia, A. ; Schuman, L. ; Stewart, W. ; Szklo, M. ; Bain, C. ; Schofield, F. ; Siskind, V. ; Band, P. ; Coldman, A. J. ; Gallagher, R. P. ; Hislop, T. G. ; Yang, P. ; Duffy, S. W. ; Kolonel, L. M. ; Nomura, A. M Y ; Oberle, M. W. ; Ory, H. W. ; Peterson, H. B. ; Wilson, H. G. ; Wingo, P. A. ; Ebeling, K. ; Kunde, D. ; Nishan, P. ; Colditz, G. ; Martin, N. ; Pardthaisong, T. ; Silpisornkosol, S. ; Theetranont, C. ; Boosiri, B. ; Chutivongse, S. ; Jimakorn, P. ; Virutamasen, P. ; Wongsrichanalai, C. ; McMichael, A. J. ; Rohan, Thomas E. ; Ewertz, M. ; Paul, C. ; Skegg, D. C G ; Boyle, P. ; Evstifeeva, M. ; Daling, J. R. ; Malone, K. ; Noonan, E. A. ; Stanford, J. L. ; Thomas, D. B. ; Weiss, N. S. ; White, E. ; Andrieu, N. ; Brêmond, A. ; Clavel, F. ; Gairard, B. ; Lansac, J. ; Piana, L. ; Renaud, R. ; Fine, S. R P ; Cuevas, H. R. ; Ontiveros, P. ; Palet, A. ; Salazar, S. B. ; Aristizabel, N. ; Cuadros, A. ; Bachelot, A. ; Lê, M. G. ; Deacon, J. ; Peto, J. ; Taylor, C. N. ; Alfandary, E. ; Modan, B. ; Ron, E. ; Friedman, G. D. ; Hiatt, R. A. ; Bishop, T. ; Kosmelj, J. ; Primic-Zakelj, M. ; Ravnihar, B. ; Stare, J. ; Beeson, W. L. ; Fraser, G. ; Allen, D. S. ; Bulbrook, R. D. ; Cuzick, J. ; Fentiman, I. S. ; Hayward, J. L. ; Wang, D. Y. ; Hanson, R. L. ; Leske, M. C. ; Mahoney, M. C. ; Nasca, P. C. ; Varma, A. O. ; Weinstein, A. L. ; Moller, T. R. ; Olsson, H. ; Ranstam, J. ; Goldbohm, R. A. ; van den Brandt, P. A. ; Apelo, R. A. ; Baens, J. ; de la Cruz, J. R. ; Javier, B. ; Lacaya, L. B. ; Ngelangel, C. A. ; La Vecchia, C. ; Negri, E. ; Marubini, E. ; Ferraroni, M. ; Gerber, M. ; Richardson, S. ; Segala, C. ; Gatei, D. ; Kenya, P. ; Kungu, A. ; Mati, J. G. ; Brinton, L. A. ; Hoover, R. ; Schairer, C. ; Spirtas, R. ; Lee, H. P. ; Rookus, M. A. ; van Leeuwen, F. V. ; Schoenberg, J. A. ; Gammon, M. D. ; Clarke, E. A. ; Jones, L. ; McPherson, K. ; Neil, A. ; Vessey, M. ; Yeates, D. ; Beral, V. ; Bull, D. ; Crossley, B. ; Hermon, C. ; Jones, S. ; Key, T. ; Lewis, C. ; Reeves, G. ; Smith, P. ; Collins, R. ; Doll, R. ; Peto, R. ; Hannaford, P. ; Kay, C. ; Rosero-Bixby, L. ; Gao, Y. T. ; Yuan, J. M. ; Wei, H. Y. ; Yun, T. ; Zhiheng, C. ; Berry, G. ; Cooper Booth, J. ; Jelihovsky, T. ; MacLennan, R. ; Shearman, R. ; Wang, Q. S. ; Baines, C. J. ; Miller, A. B. ; Wall, C. ; Lund, E. ; Stalsberg, H. ; Dabancens, A. ; Martinez, L. ; Molina, R. ; Salas, O. ; Alexander, F. E. ; Hulka, B. S. ; Chilvers, C. E D ; Bernstein, L. ; Haile, R. W. ; Paganini-Hill, A. ; Pike, M. C. ; Ross, R. K. ; Ursin, G. ; Yu, M. C. ; Adami, H. O. ; Bergstrom, R. ; Longnecker, M. P. ; Newcomb, P. ; Farley, T. M N ; Holck, S. ; Meirik, O. / 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. In: Lancet. 1996 ; Vol. 347, No. 9017. pp. 1713-1727.
@article{44a48b08081941afa87ee53c04154ebe,
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",
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.",
author = "Calle, {E. E.} and Heath, {C. W.} and Miracle-McMahill, {H. L.} and Coates, {R. J.} and Liff, {J. M.} and S. Franceschi and R. Talamini and N. Chantarakul and S. Koetsawang and D. RachawatRachawat and A. Morabia and L. Schuman and W. Stewart and M. Szklo and C. Bain and F. Schofield and V. Siskind and P. Band and Coldman, {A. J.} and Gallagher, {R. P.} and Hislop, {T. G.} and P. Yang and Duffy, {S. W.} and Kolonel, {L. M.} and Nomura, {A. M Y} and Oberle, {M. W.} and Ory, {H. W.} and Peterson, {H. B.} and Wilson, {H. G.} and Wingo, {P. A.} and K. Ebeling and D. Kunde and P. Nishan and G. Colditz and N. Martin and T. Pardthaisong and S. Silpisornkosol and C. Theetranont and B. Boosiri and S. Chutivongse and P. Jimakorn and P. Virutamasen and C. Wongsrichanalai and McMichael, {A. J.} and Rohan, {Thomas E.} and M. Ewertz and C. Paul and Skegg, {D. C G} and P. Boyle and M. Evstifeeva and Daling, {J. R.} and K. Malone and Noonan, {E. A.} and Stanford, {J. L.} and Thomas, {D. B.} and Weiss, {N. S.} and E. White and N. Andrieu and A. Br{\^e}mond and F. Clavel and B. Gairard and J. Lansac and L. Piana and R. Renaud and Fine, {S. R P} and Cuevas, {H. R.} and P. Ontiveros and A. Palet and Salazar, {S. B.} and N. Aristizabel and A. Cuadros and A. Bachelot and L{\^e}, {M. G.} and J. Deacon and J. Peto and Taylor, {C. N.} and E. Alfandary and B. Modan and E. Ron and Friedman, {G. D.} and Hiatt, {R. A.} and T. Bishop and J. Kosmelj and M. Primic-Zakelj and B. Ravnihar and J. Stare and Beeson, {W. L.} and G. Fraser and Allen, {D. S.} and Bulbrook, {R. D.} and J. Cuzick and Fentiman, {I. S.} and Hayward, {J. L.} and Wang, {D. Y.} and Hanson, {R. L.} and Leske, {M. C.} and Mahoney, {M. C.} and Nasca, {P. C.} and Varma, {A. O.} and Weinstein, {A. L.} and Moller, {T. R.} and H. Olsson and J. Ranstam and Goldbohm, {R. A.} and {van den Brandt}, {P. A.} and Apelo, {R. A.} and J. Baens and {de la Cruz}, {J. R.} and B. Javier and Lacaya, {L. B.} and Ngelangel, {C. A.} and {La Vecchia}, C. and E. Negri and E. Marubini and M. Ferraroni and M. Gerber and S. Richardson and C. Segala and D. Gatei and P. Kenya and A. Kungu and Mati, {J. G.} and Brinton, {L. A.} and R. Hoover and C. Schairer and R. Spirtas and Lee, {H. P.} and Rookus, {M. A.} and {van Leeuwen}, {F. V.} and Schoenberg, {J. A.} and Gammon, {M. D.} and Clarke, {E. A.} and L. Jones and K. McPherson and A. Neil and M. Vessey and D. Yeates and V. Beral and D. Bull and B. Crossley and C. Hermon and S. Jones and T. Key and C. Lewis and G. Reeves and P. Smith and R. Collins and R. Doll and R. Peto and P. Hannaford and C. Kay and L. Rosero-Bixby and Gao, {Y. T.} and Yuan, {J. M.} and Wei, {H. Y.} and T. Yun and C. Zhiheng and G. Berry and {Cooper Booth}, J. and T. Jelihovsky and R. MacLennan and R. Shearman and Wang, {Q. S.} and Baines, {C. J.} and Miller, {A. B.} and C. Wall and E. Lund and H. Stalsberg and A. Dabancens and L. Martinez and R. Molina and O. Salas and Alexander, {F. E.} and Hulka, {B. S.} and Chilvers, {C. E D} and L. Bernstein and Haile, {R. W.} and A. Paganini-Hill and Pike, {M. C.} and Ross, {R. K.} and G. Ursin and Yu, {M. C.} and Adami, {H. O.} and R. Bergstrom and Longnecker, {M. P.} and P. Newcomb and Farley, {T. M N} and S. Holck and O. Meirik",
year = "1996",
month = "6",
day = "22",
language = "English (US)",
volume = "347",
pages = "1713--1727",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9017",

}

TY - JOUR

T1 - Breast cancer and hormonal contraceptives

T2 - Collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies

AU - Calle, E. E.

AU - Heath, C. W.

AU - Miracle-McMahill, H. L.

AU - Coates, R. J.

AU - Liff, J. M.

AU - Franceschi, S.

AU - Talamini, R.

AU - Chantarakul, N.

AU - Koetsawang, S.

AU - RachawatRachawat, D.

AU - Morabia, A.

AU - Schuman, L.

AU - Stewart, W.

AU - Szklo, M.

AU - Bain, C.

AU - Schofield, F.

AU - Siskind, V.

AU - Band, P.

AU - Coldman, A. J.

AU - Gallagher, R. P.

AU - Hislop, T. G.

AU - Yang, P.

AU - Duffy, S. W.

AU - Kolonel, L. M.

AU - Nomura, A. M Y

AU - Oberle, M. W.

AU - Ory, H. W.

AU - Peterson, H. B.

AU - Wilson, H. G.

AU - Wingo, P. A.

AU - Ebeling, K.

AU - Kunde, D.

AU - Nishan, P.

AU - Colditz, G.

AU - Martin, N.

AU - Pardthaisong, T.

AU - Silpisornkosol, S.

AU - Theetranont, C.

AU - Boosiri, B.

AU - Chutivongse, S.

AU - Jimakorn, P.

AU - Virutamasen, P.

AU - Wongsrichanalai, C.

AU - McMichael, A. J.

AU - Rohan, Thomas E.

AU - Ewertz, M.

AU - Paul, C.

AU - Skegg, D. C G

AU - Boyle, P.

AU - Evstifeeva, M.

AU - Daling, J. R.

AU - Malone, K.

AU - Noonan, E. A.

AU - Stanford, J. L.

AU - Thomas, D. B.

AU - Weiss, N. S.

AU - White, E.

AU - Andrieu, N.

AU - Brêmond, A.

AU - Clavel, F.

AU - Gairard, B.

AU - Lansac, J.

AU - Piana, L.

AU - Renaud, R.

AU - Fine, S. R P

AU - Cuevas, H. R.

AU - Ontiveros, P.

AU - Palet, A.

AU - Salazar, S. B.

AU - Aristizabel, N.

AU - Cuadros, A.

AU - Bachelot, A.

AU - Lê, M. G.

AU - Deacon, J.

AU - Peto, J.

AU - Taylor, C. N.

AU - Alfandary, E.

AU - Modan, B.

AU - Ron, E.

AU - Friedman, G. D.

AU - Hiatt, R. A.

AU - Bishop, T.

AU - Kosmelj, J.

AU - Primic-Zakelj, M.

AU - Ravnihar, B.

AU - Stare, J.

AU - Beeson, W. L.

AU - Fraser, G.

AU - Allen, D. S.

AU - Bulbrook, R. D.

AU - Cuzick, J.

AU - Fentiman, I. S.

AU - Hayward, J. L.

AU - Wang, D. Y.

AU - Hanson, R. L.

AU - Leske, M. C.

AU - Mahoney, M. C.

AU - Nasca, P. C.

AU - Varma, A. O.

AU - Weinstein, A. L.

AU - Moller, T. R.

AU - Olsson, H.

AU - Ranstam, J.

AU - Goldbohm, R. A.

AU - van den Brandt, P. A.

AU - Apelo, R. A.

AU - Baens, J.

AU - de la Cruz, J. R.

AU - Javier, B.

AU - Lacaya, L. B.

AU - Ngelangel, C. A.

AU - La Vecchia, C.

AU - Negri, E.

AU - Marubini, E.

AU - Ferraroni, M.

AU - Gerber, M.

AU - Richardson, S.

AU - Segala, C.

AU - Gatei, D.

AU - Kenya, P.

AU - Kungu, A.

AU - Mati, J. G.

AU - Brinton, L. A.

AU - Hoover, R.

AU - Schairer, C.

AU - Spirtas, R.

AU - Lee, H. P.

AU - Rookus, M. A.

AU - van Leeuwen, F. V.

AU - Schoenberg, J. A.

AU - Gammon, M. D.

AU - Clarke, E. A.

AU - Jones, L.

AU - McPherson, K.

AU - Neil, A.

AU - Vessey, M.

AU - Yeates, D.

AU - Beral, V.

AU - Bull, D.

AU - Crossley, B.

AU - Hermon, C.

AU - Jones, S.

AU - Key, T.

AU - Lewis, C.

AU - Reeves, G.

AU - Smith, P.

AU - Collins, R.

AU - Doll, R.

AU - Peto, R.

AU - Hannaford, P.

AU - Kay, C.

AU - Rosero-Bixby, L.

AU - Gao, Y. T.

AU - Yuan, J. M.

AU - Wei, H. Y.

AU - Yun, T.

AU - Zhiheng, C.

AU - Berry, G.

AU - Cooper Booth, J.

AU - Jelihovsky, T.

AU - MacLennan, R.

AU - Shearman, R.

AU - Wang, Q. S.

AU - Baines, C. J.

AU - Miller, A. B.

AU - Wall, C.

AU - Lund, E.

AU - Stalsberg, H.

AU - Dabancens, A.

AU - Martinez, L.

AU - Molina, R.

AU - Salas, O.

AU - Alexander, F. E.

AU - Hulka, B. S.

AU - Chilvers, C. E D

AU - Bernstein, L.

AU - Haile, R. W.

AU - Paganini-Hill, A.

AU - Pike, M. C.

AU - Ross, R. K.

AU - Ursin, G.

AU - Yu, M. C.

AU - Adami, H. O.

AU - Bergstrom, R.

AU - Longnecker, M. P.

AU - Newcomb, P.

AU - Farley, T. M N

AU - Holck, S.

AU - Meirik, O.

PY - 1996/6/22

Y1 - 1996/6/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0242390079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242390079&partnerID=8YFLogxK

M3 - Article

C2 - 8656904

AN - SCOPUS:0242390079

VL - 347

SP - 1713

EP - 1727

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9017

ER -