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

Abstract

SummaryBackgroundMenarche 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.MethodsIndividual 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.FindingsBreast 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).InterpretationThe 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.FundingCancer Research UK.

Breast Cancer Thirty Years Later: A Comparative Study between A 1983-1984 AND A 2012-2013 Cohorts of Argentine Women

“…In both almost 2/3 of the BC corresponds to menopausal women; there is also a coincidence in the age of menarche. These two data show that both series are quite comparable to each other and with most reported worldwide series from "western societies" [37]; it, also, allows us to suppose that they would be BC cases due, mainly, to recognized hormonal risk factors [38,39]. In the reproductive history of patients there is also a remarkable similarity inthe percentage of nulliparous women; this recognized and accepted "risk factor" is strongly associated with BC in postmenopausal women [40,41] as are most of the patients in both series.…”

Structured additive regression modeling of age of menarche and menopause in a breast cancer screening program

“…showed the increasing incidence rates in developing countries and the importance of reproductive factors. Recent works by Talma et al (2013), Berman et al (2012), Rigon et al (2010), and Cabanes et al (2009) add to the ongoing discussion on whether the age of menarche is decreasing in countries such as in the Netherlands, Israel, Italy, and Spain. Studies in spatial epidemiology have focused on finding spatial patterns in mortality and incidence of breast cancer and the corresponding association with risk factors.…”

Contribution of the Endocrine Perspective in the Evaluation of Endocrine Disrupting Chemical Effects: The Case Study of Pubertal Timing

“…Moreover, early puberty is linked with increased risk of sexual abuse [25]. In the long term, early and precocious timing of puberty also predicts a slight but significant increase in the risk of breast cancer [26]. An association between early puberty and increased risk of angina, hypertension and type 2 diabetes, among others, has been described recently [27].…”