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The review analyzes up-to-date information about specific characteristics of anti-estrogen therapeutic agents with different mechanisms of action with regard to present knowledge of endocrine therapy for estrogen-positive breast cancer (ER+ BC). The paper presents some agents for anti-estrogen therapy of breast cancer - aromatase inhibitors and selective modifiers of biological reactions (SMBR) and their mechanisms of anti-proliferative action. The authors describe significant therapeutic and side effects as well as different options for anti-estrogen combinations. Special emphasis is made on national herbal estrogens/anti-estrogens that have no toxicity associated with the well-known SMBRs. The review presents the structure and characteristics of a perspective phyto-anti-estrogen sekoizolaricirezinol (SEKO), which demonstrated significant anti-proliferative activity with no pro-estrogen action in the in vivo models of ER+ BC.