In Japan, the incidence of breast cancer is remarkably lower than in Western countries. We examined tumor estrogen (ER) and progesterone receptors (PgR) in 1060 Japanese breast cancer patients. In Japan, 58% and 36% of breast cancers revealed measurable amounts of cytosol ER and PgR, respectively. These rates are slightly lower than those reported in Western countries, which were found to be 60-80% and 40-60%, respectively, though the difference is mainly confined to postmenopausal non-overweight (less than 60 kg) patients. The objective remission rates to endocrine therapy were 48% for ER+ tumors, 10% for ER-tumors, 66% for ER+, PgR+ tumors, 30% for ER+, PgR- tumors and 10% for ER-, PgR- tumors. These response rates are similar to those in Western breast cancer patients. ER and/or PgR in the breast cancer cytosol are useful markers for predicting response to endocrine therapy. The present findings also indicate that ER- tumors are estrogen independent but ER+ tumors include both estrogen-dependent and -independent tumors and that some of ER+ but endocrine-resistant tumors have postreceptor defect. The presence of ER+ but endocrine-resistant tumors may be due in part to the loss of hormone-dependency of estrogen-dependent breast cancer during endocrine therapy. The transformation of hormone-dependent mouse tumor cells into independent tumor cells was demonstrated as one of the mechanisms involved in the loss of hormone-dependency.