A novel pure SERM achieves complete regression of the majority of human breast cancer tumors in nude mice.
BACKGROUND
The objective was to determine if EM-652, a novel selective estrogen receptor modulator (SERM) having highly potent and pure antiestrogenic activity in the mammary gland could cause complete regression of the majority of human breast cancer xenografts in nude mice.


METHODS
Human breast cancer ZR-75-1 xenografts were used as model in nude mice.


RESULTS
EM-652 not only prevented estrogen-induced tumor growth but it reduced tumor size to 20% of the pretreatment value. Complete disappearance of the tumors was observed in 65% (106/163) of tumors. No tumor progressed. Most importantly, 93% of the tumors which had become undetectable under EM-652 treatment did not reappear when exposed to estrogen challenge for 12 weeks, thus achieving an overall 61% cure rate.


CONCLUSIONS
The present data demonstrate that EM-652 is strongly cytotoxic or tumorocidal and not only cytostatic or tumorostatic in estrogen-sensitive breast cancer, thus changing the paradigm of a tumorostatic role of estrogen blockade established with tamoxifen. These findings support the use of such a compound for more efficient breast cancer prevention and therapy.
Roy
Jenny
J
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), Laval University, Quebec City, Que., Canada.
Couillard
Steeve
S
Gutman
Mathieu
M
Labrie
Fernand
F
D000704:Analysis of Variance; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D002277:Carcinoma / Q000188:drug therapy* / Q000517:prevention & control; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010880:Piperidines / Q000494:pharmacology*; D012008:Recurrence; D012074:Remission Induction; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
D004968:Estrogens, Non-Steroidal; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; C012121:ritetronium