Extratumoral breast tissue in breast cancer patients: a multinational study of variations with age and country of residence in low- and high-risk countries. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

With the aim of elucidating the relationships between breast cancer, risk factors and benign breast changes, extratumoral breast tissue in 1,506 women from the WHO Collaborative study of neoplasia and steroid contraceptives was studied histologically. Patients came from 3 countries with a high incidence of breast cancer (Israel, East Germany and Australia) and 6 low-risk countries (Thailand, China, Philippines, Mexico, Chile and Colombia). Ductal atypia, ductal hyperplasia, adenosis, lobular atypia, apocrine metaplasia, apocrine hyperplasia, apocrine atypia, cysts, duct ectasia, inflammatory reaction, calcification, lactational change and epithelial-stromal ratio were classified as absent/mild/moderate/marked. Prevalence odds ratios were calculated by logistic regression analyses. Increasing frequency with age was found for ductal hyperplasia, sclerosing adenosis, apocrine metaplasia and cysts, while adenosis, lactational change and the epithelial-stromal ratio decreased with age. No significant difference between high- and low-risk countries was found for ductal hyperplasia or sclerosing adenosis. Compared with cases from high-risk countries, those from low-risk countries had a significantly lower prevalence of apocrine metaplasia, apocrine hyperplasia and cysts, and a significantly higher prevalence of ductal atypia. When seen in conjunction with other studies, the results suggest that ductal hyperplasia and sclerosing adenosis have similar roles in cancer development in high- and low-risk countries and that the factors responsible for international differences in breast cancer may exert their effect by influencing the initial development of these changes. They also suggest a delayed progression from noninvasive to invasive carcinoma in low-risk countries.