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

Neugut, A. ; Santella, R. ; Baines, C. J. ; Kreiger, N. ; Miller, A. B. ; Wall, C. ; Tjonneland, A. ; Jorgensen, T. ; Stahlberg, C. and Pedersen, A. Tonnes , et al. (2012) In The Lancet Oncology 13(11). p.1141-1151
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... (More)
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. (Less)
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The Lancet Oncology
volume
13
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11
pages
1141 - 1151
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Elsevier
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  • wos:000310570900045
  • scopus:84877875905
ISSN
1474-5488
DOI
10.1016/S1470-2045(12)70425-4
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English
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@article{9ba9ccc8-a2f0-4ed6-8e1d-2b4305913e80,
  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 &lt; 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p &lt; 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 &lt; 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 &lt; 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 &lt; 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.},
  author       = {Neugut, A. and Santella, R. and Baines, C. J. and Kreiger, N. and Miller, A. B. and Wall, C. and Tjonneland, A. and Jorgensen, T. and Stahlberg, C. and Pedersen, A. Tonnes and Flesch-Janys, D. and Hakansson, N. and Cauley, J. and Heuch, I. and Adami, H. O. and Persson, I. and Weiderpass, E. and Magnusson, C. and Chang-Claude, J. and Kaaks, R. and McCredie, M. and Paul, C. and Skegg, D. C. G. and Spears, G. F. S. and Iwasaki, M. and Tsugane, S. and Anderson, G. and Daling, J. R. and Hampton, J. and Hutchinson, W. B. and Li, C. I. and Malone, K. and Mandelson, M. and Newcomb, P. and Noonan, E. A. and Ray, R. M. and Stanford, J. L. and Tang, M. T. C. and Thomas, D. B. and Weiss, N. S. and White, E. and Izquierdo, A. and Viladiu, P. and Fourkala, E. O. and Jacobs, I. and Menon, U. and Ryan, A. and Cuevas, H. R. and Hartmann, Michael},
  issn         = {1474-5488},
  language     = {eng},
  number       = {11},
  pages        = {1141--1151},
  publisher    = {Elsevier},
  series       = {The Lancet Oncology},
  title        = {Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies},
  url          = {http://dx.doi.org/10.1016/S1470-2045(12)70425-4},
  doi          = {10.1016/S1470-2045(12)70425-4},
  volume       = {13},
  year         = {2012},
}