Estriol therapy of metastatic breast cancer

Reduced estriol (E3)/estrone + estradiol 17B excretion is present in Caucasians as compared to Asiatics, and Caucasian women with chronic cystic disease or untreated breast carcinoma are 3 times as likely as controls to excrete subnormal estriol quotients. E3 20 to 30 mcg/Kg/day specifically prevents 90% of chemically induced breast carcinoma during the natural life span of intact female rats (p<.001), probably by displacement of estradiol from breast estrophile proteins. None of 18 other steroids was as effective at this dosage. To evaluate feasibility of chronic E3 therapy, 2.5 to 5.0 mg daily were fed once daily to 18+ breast cancer patients aged 51 to 74. Median vaginal cornified cells increased from 2% to 21% with endometrial bleeding in 3. Minimal increase in serum total lipids and in triglyceride fraction was noted in 3/5 patients. Increased bone pain from osseous lesions stopped therapy in 3 patients. No nausea, hypertension, edema or weight gains occurred. Clinical arrest of lung, bone or skin metastases without new lesions was noted in 3 patients treated for 2.5 to 11.0 mth. More than 25% reduction in 2 diameters of skin metastases without new lesions was noted in 3 additional patients lasting 5 to 10 mth. The feasibility and safety of chronic oral E3 therapy in women has been demonstrated.