Abstract A98: Zinc transporter activation and the later age of lactation may increase the risk for breast cancer

Breast cancer (BC) is the leading form of cancer among American women. African American women (AAW) are twice as likely to die from breast cancer compared to European American women (EAW), who have a higher incidence of developing BC than AAW. Approximately 90% of breast cancer occurs sporadically without any apparent predisposing genetic alterations while the remaining BC cases are inheritable. Breast development is a vital part of the female reproduction. Breast development occurs in distinct stages throughout a woman9s life, first before birth, and again at puberty and during the childbearing years. Hormonal levels gradually increase and peak during puberty and each are continuously enhancing during pregnancy and lactation; however, during menopause each hormone starts to fluctuate which leads to a dramatic decline of the hormones. A significant percent of women in the industrial nations take hormone replacement therapy (estrogen-progestin), putting them at higher risk for BC. As an essential mineral, Zn is required for numerous metabolic processes including the regulation of many proteins involved in DNA and protein synthesis, mitosis and cell division, serving both a structural and catalytic role. In addition to regulating basic cellular function, the tight regulation of Zn transport in the mammary gland is critical for optimal Zn transfer into milk during lactation. Zinc demands in the breast peaks during the lactation phase. Dysregulation of mammary gland Zn metabolism has recently been associated with BC. McCormack and dos Santos Silva have reviewed the data regarding the association on the percentage of mammographic density (PMD) with the risk of breast cancer in a systematic meta-analysis of data for >14,000 cases and 226,000 non-cases obtained from 42 studies. They found that PMD was consistently associated with the risk of breast cancer and these associations were found to be stronger in the studies within the general population rather than in symptomatic women. The distribution of PMD changes with increasing age reflecting the reduction in glandular tissue and accompanying increase in fat that occurs with increasing age. All current methods of assessing the density have advantages and disadvantages, and no method is ideal. All methods have measurement errors. Densities on the digital and film mammograms are not identical. The decline in density with age may seem paradoxical, as the incidence of BC increases with age, but this apparent paradox may be resolved by referencing a model for BC incidence proposed by Pike and colleagues. Their model is based on the concept on breast tissue exposure rather than chronological age of woman, is the relevant measure for describing the incidence of BC. We propose a modification of the model and that the breast tissue age is closely associated with the exposure of the breast tissue to hormones, growth factors, the balanced amount of zinc, and age at the peak activation of zinc transporters and to the effects that menarche, pregnancy and menopause have on these exposures and on the susceptibility to carcinogens. We therefore theorize that based on age, ethnicity, and maturity of the breast determines the risk for breast cancer in reference to the hormonal-induced activation of zinc transporters that are critical for zinc transport that control zinc homeostasis during lactation and are affected by the age a woman begins lactation. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A98.