Epidemiologic studies have been consistent in showing early age at menarche as a risk factor for breast cancer. A 5% decrease in breast cancer risk results from each year that menarche is delayed.14 A number of studies have provided evidence that the timing of menarche is associated with levels of endogenous estrogens in later adulthood.15 Early menarche results in early onset of regular ovulatory menstrual cycles,16 and consequently into an extended exposure to reproductive hormones.17 Over the past 100 years, age at menarche has progressively decreased in the U.S. and in most other areas of the world. It is possible that improved nutrition and control of infectious diseases of childhood may have led to lower ages at menarche, and increasing breast cancer incidence over the past century.
At the time of menopause, age-specific incidence rates of breast cancer slow markedly, and the rate of increase in the postmenopausal period is only about one sixth the rate of increase in the premenopausal period. In their study, Tri-chopolous and colleagues18 found that women who experienced natural menopause (defined as cessation of periods) before age 45 had only one half the breast cancer risk of those whose menopause occurred after age 55.
Parity, and in particular early age at first full-term pregnancy, are associated with decreased breast cancer risk. Pregnancy causes a transient increase in breast cancer risk, followed by a lasting protective effect.19 In one international case-control study, women with a first birth before the age of 20 had about one half the risk of nulliparous women.20 The first full-term birth has the strongest effect on breast cancer risk; however, there is an additional protective effect of subsequent births.21 The association of parity with a lasting decrease in breast cancer risk may be due to a favorable change in the susceptibility of breast tissue to carcinogenesis resulting from maturation and differentiation of breast tissue in response to hormonal events occurring during pregnancy.22 It is also true that there are some lasting changes in hormonal milieu following pregnancy. Free estradiol and prolactin levels are lower and sex hormone-binding globulin (SHBG) levels are higher in parous compared to nulliparous women.23 24
Lactation is associated with a reduction in breast cancer risk. Nursing results in a delay in the reestablishment of ovulation after a full-term pregnancy. The Collaborative Group on Hormonal Factors in Breast Cancer conducted a pooled analysis of 47 epidemiologic studies done in 30 countries and found a decrease of 4.3% in breast cancer risk associated with each 12 months of breastfeeding, in addition to an independent decrease in risk associated with bearing each child.25
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