The shape of age-incidence curves of female breast cancer by hormone-receptor status

Objectives: Substantial decline of ovarian hormones at menopause plays an i mportant role in breast cancer etiology. Hormones must bind to specific rec eptors to elicit biological responses, however. We therefore hypothesized a nd examined whether the age-specific risk of breast cancer, especially its change at menopause, differs by estrogen and progesterone receptor (ER/PR) status. Methods: Age-specific incidence rates, stratified by ER/PR status, were est imated by multiplying the age-specific ER/PR distribution among 3359 cases in the Danish Breast Cancer Cooperative Group by Danish national age-specif ic incidence rates. International variations in the age-incidence curve wer e also reviewed in relation to the hypothesis. Results: The incidence of ER + /PR + subtype (62.9% of all cases) increased with age continually, with a sudden decrease in the rate of increase aroun d age 44. The incidence of ER - /PR - subtype (17.6%) increased with age pr ior to about age 50 but remained unchanged subsequently. The incidence of E R + /PR- subtype (13.9%) increased rapidly during the menopausal period but only slightly afterwards. The incidence of ER - /PR + subtype (5.6%) incre ased until about age 43 and decreased subsequently. The international compa rison revealed Western women, particularly the elderly, might be at substan tially higher risk for ER + /PR + subtype compared to Japanese women. Conclusion: Age-specific risk of breast cancer differs by ER/PR status. The large international variation of breast cancer incidence rates may be expl ained largely by the risk difference for ER + /PR + subtype.