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

No Authors Listed

doi:10.1016/S1470-2045(12)70425-4

The Lancet. Oncology, 13(11), 1141-1151, 2012

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

Collaborative Group on Hormonal Factors in Breast Cancer , No Authors Listed

Author affiliations

Cancer Epidemiology Unit, Richard Doll Building, Oxford OX3 7LF, UK. collaborations@ceu.ox.ac.uk

DOI10.1016/S1470-2045(12)70425-4 PMID23084519

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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.

Topics

Reproductive Endocrinology Menstrual Cycle

menarche age breast cancer risk, menopause age breast cancer, reproductive factors breast cancer, individual participant meta-analysis breast cancer, hormonal exposure breast cancer, age at menarche cancer risk, menstrual lifetime breast cancer, estrogen exposure duration cancer, epidemiological study breast cancer risk factors, reproductive history cancer risk

PMID 23084519 23084519 DOI 10.1016/S1470-2045(12)70425-4 10.1016/S1470-2045(12)70425-4

Cite this article

Collaborative Group on Hormonal Factors in Breast Cancer (2012). Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. The Lancet. Oncology, 13(11), 1141-1151. https://doi.org/10.1016/S1470-2045(12)70425-4

Keywords

Estrogens, Receptors, Estrogen

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