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1. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies

Author

Beral, V, Bull, D, Pirie, K, Reeves, G, Peto, R, Skegg, D, LaVecchia, C, Magnusson, C, Pike, MC, Thomas, D, Hamajima, N, Hirose, K, Tajima, K, Rohan, T, Friedenreich, CM, Calle, EE, Gapstur, SM, Patel, AV, Coates, RJ, Liff, JM, Talamini, R, Chantarakul, N, Koetsawang, S, Rachawat, D, Marcou, Y, Kakouri, E, Duffy, SW, Morabia, A, Schuman, L, Stewart, W, Szklo, M, Coogan, PF, Palmer, JR, Rosenberg, L, Band, P, Coldman, AJ, Gallagher, RP, Hislop, TG, Yang, P, Cummings, SR, Canfell, K, Sitas, F, Chao, P, Lissowska, J, Horn-Ross, PL, John, EM, Kolonel, LM, Nomura, AMY, Ghiasvand, R, Hu, J, Johnson, KC, Mao, Y, Callaghan, K, Crossley, B, Goodill, A, Green, J, Hermon, C, Key, T, Lindgard, I, Liu, B, Collins, R, Doll, R, Bishop, T, Fentiman, IS, De Sanjose, S, Gonzaler, CA, Lee, N, Marchbanks, P, Ory, HW, Peterson, HB, Wingo, P, Ebeling, K, Kunde, D, Nishan, P, Hopper, JL, Eliassen, H, Gajalakshmi, V, Martin, N, Pardthaisong, T, Silpisornkosol, S, Theetranont, C, Boosiri, B, Chutivongse, S, Jimakorn, P, Virutamasen, P, Wongsrichanalai, C, Neugut, A, Santella, R, Baines, CJ, Kreiger, N, Miller, AB, Wall, C, Tjonneland, A, Jorgensen, T, Stahlberg, C, Pedersen, AT, Flesch-Janys, D, Hakansson, N, Cauley, J, Heuch, I, Adami, HO, Persson, I, Weiderpass, E, Chang-Claude, J, Kaaks, R, McCredie, M, Paul, C, Skegg, DCG, Spears, GFS, Iwasaki, M, Tsugane, S, Anderson, G, Daling, JR, Hampton, J, Hutchinson, WB, Li, CI, Malone, K, Mandelson, M, Newcomb, P, Noonan, EA, Ray, RM, Stanford, JL, Tang, MTC, Thomas, DB, Weiss, NS, White, E, Izquierdo, A, Viladiu, P, Fourkala, EO, Jacobs, I, Menon, U, Ryan, A, Cuevas, HR, Ontiveros, P, Palet, A, Salazar, SB, Aristizabal, N, Cuadros, A, Tryggvadottir, L, Tulinius, H, Riboli, E, Andrieu, N, Bachelot, A, Le, MG, Bremond, A, Gairard, B, Lansac, J, Piana, L, Renaud, R, Clavel-Chapelon, F, Fournier, A, Touillaud, M, Mesrine, S, Chabbert-Buffet, N, Boutron-Ruault, MC, Wolk, A, Torres-Mejia, G, Franceschi, S, Romieu, I, Boyle, P, Lubin, F, Modan, B, Ron, E, Wax, Y, Friedman, GD, Hiatt, RA, Levi, F, Kosmelj, K, Primic-Zakelj, M, Ravnihar, B, Stare, J, Ekbom, A, Erlandsson, G, Beeson, WL, Fraser, G, Peto, J, Hanson, RL, Leske, MC, Mahoney, MC, Nasca, PC, Varma, AO, Weinstein, AL, Hartman, ML, Olsson, H, Goldbohm, RA, van den Brandt, PA, Palli, D, Teitelbaum, S, 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, Freedman, M, Hoover, R, Schairer, C, Ziegler, R, Banks, E, Spirtas, R, Lee, HP, Rookus, MA, van Leeuwen, FE, Schoenberg, JA, Graff-Iversen, S, Selmer, R, Jones, L, McPherson, K, Neil, A, Vessey, M, Yeates, D, Mabuchi, K, Preston, D, Hannaford, P, Kay, C, McCann, SE, Rosero-Bixby, L, Gao, YT, Jin, F, Yuan, J-M, Wei, HY, Yun, T, Zhiheng, C, Berry, G, Booth, JC, Jelihovsky, T, MacLennan, R, Shearman, R, Hadjisavvas, A, Kyriacou, K, Loisidou, M, Zhou, X, Wang, Q-S, Kawai, M, Minami, Y, Tsuji, I, Lund, E, Kumle, M, Stalsberg, H, Shu, XO, Zheng, W, Monninkhof, EM, Onland-Moret, NC, Peeters, PHM, Katsouyanni, K, Trichopoulou, A, Trichopoulos, D, Tzonou, A, Baltzell, KA, Dabancens, A, Martinez, L, Molina, R, Salas, O, Alexander, FE, Anderson, K, Folsom, AR, Gammon, MD, Hulka, BS, Millikan, R, Chilvers, CED, Lumachi, F, Bain, C, Schofield, F, Siskind, V, Rebbeck, TR, Bernstein, LR, Enger, S, Haile, RW, Paganini-Hill, A, Ross, RK, Ursin, G, Wu, AH, Yu, MC, Ewertz, DM, Clarke, EA, Bergkvist, L, Anderson, GL, Gass, M, O'Sullivan, MJ, Kalache, A, Farley, TMM, Holck, S, Meirik, O, Fukao, A, Factors, CGH, Grp, SHNHSIIIR, Epidemiologie, RS: CAPHRI School for Public Health and Primary Care, RS: GROW - School for Oncology and Reproduction, RS: GROW - R1 - Prevention, RS: CAPHRI - R5 - Optimising Patient Care, and Collaborative Group on Hormonal Factors in Breast Cancer

Subjects
Aging, Breast cancer, Risk factors, Menopause, Menarche, cancer, malignancy, Ethnic origin, Disease, 0302 clinical medicine, Breast cancer, Risk Factors, Neoplasms, Receptors, Epidemiology, 80 and over, 030212 general & internal medicine, skin and connective tissue diseases, Aged, 80 and over, Patient, Obstetrics, Reproduction, Smoking, Age Factors, Middle Aged, Reproducibility, 3. Good health, Menopause, Receptors, Estrogen, Oncology, 030220 oncology & carcinogenesis, Menarche, Hormonal therapy, Female, epidemiology, Cancer Type - Breast Cancer, history, Adult, Risk, trends, medicine.medical_specialty, Design, Neoplasms, Hormone-Dependent, Requiring prolonged observation, Hormone Replacement Therapy, Oncology and Carcinogenesis, Breast Neoplasms, and over, Validity, methods, 03 medical and health sciences, Age, Clinical Research, Breast Cancer, medicine, Humans, cancer, Neoplasm Invasiveness, Women, Oncology & Carcinogenesis, Hormone-Dependent, breast, Aged, Gynecology, Collaborative Group on Hormonal Factors in Breast Cancer, therapy, business.industry, Contraception/Reproduction, Research, Estrogens, Etiology - Resources and Infrastructure, medicine.disease, Estrogen, Good Health and Well Being, cessation, Premenopause, Risk factors, Relative risk, Recall, business, malignancy, Meta-Analysis
Abstract

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons).Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.Funding Cancer Research UK.

Published
2012
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2. Breast cancer and hormonal contraceptives: Further results

Author

Calle, Ee, Heath, Cw, Miraclemcmahill, Hl, Coates, Rj, Liff, Jm, Franceschi, S., Talamini, R., Chantarakul, N., Koetsawang, S., Rachawat, D., Morabia, A., Schuman, I., 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, T., Ewertz, M., Paul, C., Skegg, Dcg, Spears, Gfs, Boyle, P., Evstifeeva, T., Daling, Jr, Malone, K., Noonan, Ea, Stanford, Jl, Thomas, Db, Weiss, Ns, White, E., Andrieu, N., Bremond, 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., Le, Mg, Deacon, J., Peto, J., Taylor, Cn, Alfandary, E., Modan, B., Ron, E., Friedman, Gd, Hiatt, Ra, Bishop, T., Kosmelj, K., Primiczakelj, 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, Ap, Weinstein, Al, Moller, Tr, Olsson, H., Ranstam, J., Goldbohm, Ra, Vandenbrandt, Pa, Apelo, Ra, Baens, J., Delacruz, Jr, Javier, B., Lacaya, Lb, Ngelangel, Ca, Lavecchia, C., Eva Negri, Marbuni, 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, Vanleeuwen, Fe, 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., Roserobixby, L., Yuan, Jm, Wei, Hy, Yun, T., Zhiheng, C., Berry, G., Booth, Jc, 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, Paganinihill, A., Pike, Mc, Ross, Rk, Ursin, G., Yu, Mc, Adami, Ho, Bergstrom, R., Longnecker, Mp, Newcomb, P., Farley, Tmn, Holck, S., Meirik, O., Calle EE, Heath CW, MiracleMcMahill HL, Coates RJ, Liff JM, Franceschi S, Talamini R, Chantarakul N, Koetsawang S, Rachawat D, Morabia A, Schuman I, 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 T, Ewertz M, Paul C, Skegg DCG, Spears GFS, Boyle P, Evstifeeva T, Daling JR, Malone K, Noonan EA, Stanford JL, Thomas DB, Weiss NS, White E, Andrieu N, Bremond 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, Le MG, Deacon J, Peto J, Taylor CN, Alfandary E, Modan B, Ron E, Friedman GD, Hiatt RA, Bishop T, Kosmelj K, PrimicZakelj 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 AP, Weinstein AL, Moller TR, Olsson H, Ranstam J, Goldbohm RA, vandenBrandt PA, Apelo RA, Baens J, delaCruz JR, Javier B, Lacaya LB, Ngelangel CA, LaVecchia C, Negri E, Marbuni 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, vanLeeuwen FE, 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, RoseroBixby L, Yuan JM, Wei HY, Yun T, Zhiheng C, Berry G, Booth JC, 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, PaganiniHill A, Pike MC, Ross RK, Ursin G, Yu MC, Adami HO, Bergstrom R, Longnecker MP, Newcomb P, Farley TMN, Holck S, and Meirik O

Abstract

The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on breast cancer risk and use oi hormonal contraceptives. Original data from 54 studies, representing about 90% of the information available on the topic, were collected, checked and analysed centrally. The 54 studies were performed in 26 countries and include a total of 53,297 women with breast cancer and 100,239 women without breast cancer. The studies were varied in their design, setting and timing. Most information came from case-control studies with controls chosen from the general population; most women resided in Europe or North America and most cancers were diagnosed during the 1980s. Overall 41% of the women with breast cancer and 40% of the women without breast cancer had used oral contraceptives at some time: the median age at first use was 26 years, the median duration of use was 3 years, the median year of first use was 1968, the median time since first use was 16 years, and the median time since last use was 9 years. The main findings, summarised elsewhere,I are that there is a small increase in the risk of having breast cancer diagnosed in current users of combined oral contraceptives and in women who had stopped use in the past 10 years but that there is no evidence of an increase in the risk more than 10 years after stopping use. In addition, the cancers diagnosed in women who had used oral contraceptives tended to be less advanced clinically than the cancers diagnosed in women who had not used them. Despite the large number of possibilities investigated, few factors appeared to modify the main findings either in recent or in past users. For recent users who began use before age 20 the relative risks are higher than for recent users who began at older ages. For women whose use of oral contraceptives ceased more than 10 years before there was some suggestion of a reduction in breast cancer risk in certain subgroups, with a deficit of tumors that had spread beyond the breast, especially among women who had used preparations containing the highest doses of oestrogen and progestogen. These findings are unexpected and need to be confirmed. Although these data represent most of the epidemiologi cal evidence on the topic to date, there is still insufficient information to comment reliably about the effects of specific types of oestrogen or of progestogen. What evidence there is suggests, however, no major differences in the effects for specific types of oestrogen or of progestogen and that the pattern of risk associated with use of hormonal contraceptives containing progestogens alone may be similar to that observed for preparations containing both oestrogens and progestogens. On the basis of these results, there is little difference between women who have and have not used combined oral contraceptives in terms of the estimated cumulative number of breast cancers diagnosed during the period from starting use up to 20 rears after stopping. The cancers diagnosed in women who have used oral contraceptives are, however, less advanced clinically than the cancers diag nosed in never users. Further research is needed to establish whether the associations described here are due to earlier diagnosis of breast cancer in women who have used oral contraceptives, to the biological effects of the hormonal contraceptives or to a combination of both. Little information is as yet available about the effects on breast cancer risk of oral contraceptive use that ceased more than 20 years before and as such data accumulate it will be necessary to reexamine the worldwide evidence. RI Ranstam, Jonas/A-4386-2009; Colditz, Graham/A-3963-2009

Published
1996

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