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
Published November 2012The Lancet. Oncology, 13(11), 1141-1151
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
Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol. 2012;13(11):1141-1151. doi:10.1016/S1470-2045(12)70425-4
Collaborative Group on Hormonal Factors in Breast Cancer. "Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies." The Lancet. Oncology, vol. 13, no. 11, 2012, pp. 1141-1151.
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Author affiliations
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Cancer Epidemiology Unit, Richard Doll Building, Oxford OX3 7LF, UK. collaborations@ceu.ox.ac.uk
RRM Academy Synopsis
Earlier menarche and later menopause are linked to breast cancer risk
A 2012 pooled analysis of 117 studies, including 118 964 women with breast cancer and 306 091 without, found that breast cancer risk rose with earlier menarche and with later menopause. Among women aged 45–54, those not yet postmenopausal had a higher risk than postmenopausal women.
Key Findings
Relative risk of breast cancer was multiplied by 1·050 (95% CI 1·044–1·057, p<0·0001) with each year of earlier menarche.
Among postmenopausal women, each year older at menopause multiplied the relative risk by 1·029 (1·025–1·032, p<0·0001).
In women aged 45–54 years, premenopausal women carried more risk than postmenopausal women of the same age (RR 1·43, 95% CI 1·33–1·52, p<0·0001).
Lobular cancers showed stronger links than ductal cancers on all three measures, and the menopause findings were stronger for estrogen receptor-positive disease.
Higher body fat was associated with weaker links on all three measures among postmenopausal women, while birth year, ethnic origin, childbearing, smoking, drinking, and hormonal contraceptive use made no material difference.
Interpretation
The collaboration combined data on individual women from 117 studies in 35 countries, mainly from Europe or North America. The analysis left out women who had used hormone therapy for menopause. Among postmenopausal women, risk was higher by a significantly greater amount per year of earlier menarche than per year of later menopause (1·045 [1·036–1·054] versus 1·029 [1·025–1·032]; heterogeneity p=0·001). The authors conclude that the two events may not affect risk merely by lengthening total reproductive years. They also note that women recalled their ages at these events many years afterward, which the authors say would dilute the risk estimates.
RRM Context
Menarche and menopause mark the start and end of ovarian hormone production. Restorative reproductive medicine treats the menstrual cycle as a vital sign of ovarian health. The cycle therefore carries information about hormones that matter across a woman's whole life.
Our editorial summary of this paper, not the article's abstract.
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.
General Gynecology › Breast Health › Breast Cancer Risk · Longevity and Reproductive Aging › Reproductive Aging › Ovarian Aging · Reproductive Endocrinology › Ovarian Hormones › Estrogen
PMID 23084519 23084519 DOI 10.1016/S1470-2045(12)70425-4 10.1016/S1470-2045(12)70425-4 Collaborative Group on Hormonal Factors in Breast Cancer et al. 2012, Collaborative Group on Hormonal Factors in Breast Cancer 2012
