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

Objectives: Substantial decline of ovarian hormones at menopause plays an important role in breast cancer etiology. Hormones must bind to specific receptors to elicit biological responses, however. We therefore hypothesized and 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 estimated by multiplying the age-specific ER/PR distribution among 3359 cases in the Danish Breast Cancer Cooperative Group by Danish national age-specific incidence rates. International variations in the age-incidence curve were 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 around age 44. The incidence of ER - /PR - subtype (17.6%) increased with age prior to about age 50 but remained unchanged subsequently. The incidence of ER + /PR- subtype (13.9%) increased rapidly during the menopausal period but only slightly afterwards. The incidence of ER - /PR + subtype (5.6%) increased until about age 43 and decreased subsequently. The international comparison revealed Western women, particularly the elderly, might be at substantially 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 explained largely by the risk difference for ER + /PR + subtype.