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Chemopreventive Efficacy of Combined Retinoid and Tamoxifen Treatment following Surgical Excision of a Primary Mammary Cancer in Female Rats¹

Laboratory of Pathophysiology, Life Sciences Division, IIT Research Institute, Chicago, Illinois 60616 [T. A. R., C. J. D., N. M. D., C. F. T., R. C. M.], and National Cancer Institute, Chemoprevention Branch, Bethesda, Maryland 20892 [G. J. K.]

Dietary N-(4-hydroxyphenyl)retinamide (4-HPR; 3 mmol/kg diet) and s.c. injections of the antiestrogen, tamoxifen (Tx; 10 µg or 20 µg per rat, thrice weekly) were used together as adjunct chemopreventive therapy in groups of 39–40 female, Sprague-Dawley rats that each received an i.v. injection (50 mg/kg b.w.) of the mammary gland carcinogen N-methyl-N-nitrosourea (MNU). Treatment was started immediately following the surgical excision of the first (primary) mammary carcinoma from each MNU-treated rat and was continued for 180 days. When compared to the effect of treatment with 4-HPR or Tx (30 µg/wk) alone, the combination treatments significantly enhanced terminal survival and reduced nonrecurrent mammary cancer incidence and multiplicity. Data showing the incidence of rats bearing the first through fifth additional cancers to appear following surgical resection of a primary lesion demonstrate that combined treatment with 4-HPR/Tx was immediately and consistently more efficacious than either agent per se in suppressing subsequent tumor appearance. This effect was apparently related to the dose of Tx. These results suggest that combined treatment with 4-HPR/Tx is superior to that of either agent alone in blocking progression of incipient neoplastic lesions at both early and later stages of the process.

¹ Supported in part by Contract N01-CN-45192-02 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Life Sciences Division, IIT Research Institute, 10 West 35th Street, Chicago, IL 60616.

Received 12/19/88. Revised 4/ 3/89. Accepted 5/18/89.

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