Tamoxifen in breast cancer

Clark, A.S., West, K., Streicher, S., and Dennis, P.A. 2002. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells Mol Cancer Ther 1 707-717. 

Shenoy DB, Amiji MA (2005) Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer. International Journal of... 

Tamoxifen is a partial estrogen agonist in breast and thus is used as a treatment and chemopreventative for breast cancer. Tamoxifen is a full agonist in bone and endometrium, and prolonged use of tamoxifen leads to a fourfold to fivefold increase in the incidence of endometrial cancer. See Chapter 56 for a detailed discussion of the use of tamoxifen in breast cancer. 

This study has again confirmed that endometrial problems can be induced by tamoxifen early in the course of treatment and that these problems do not arise with aromatase inhibitors, which may actually reduce the endometrial changes induced by tamoxifen. The idea that the new oral aromatase inhibitors might well replace tamoxifen in breast cancer was tentatively advanced in SEDA-26 (p. 445) and has now been supported by some of the material cited above, as well as by a panel consensus (25). Citing efficacy and safety data on anastrozole, exemestane, and letrozole, the authors concluded that third-generation aromatase inhibitors may be considered first-line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women and may also be used for preoperative therapy of breast cancer. 

Concern was expressed that such a conclusion could lead to even wider hesitation to use tamoxifen in breast cancer, despite the fact that it is already used very selectively, for example in women with positive estrogen... 

Arnold BJ, Cumming CE, Lees AW, Handman MD, Cumming DC, Urion C. Tamoxifen in breast cancer symptom reporting. Breast J 2001 7(2) 97-100. 

Tucker AN et al (2005) Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett 217 61-72... 

Poon GK et al (1993) Analysis of phase I and phase II metabolites of tamoxifen in breast cancer patients. Drug Metab Dispos 21 1119-1124... 

Stimulated by the need for an improved therapy for breast cancer, considerable efforts have been devoted to the synthesis of compounds that would exert pure antiestrogenic activity in the mammary gland and uterus. As mentioned above, while tamoxifen has beneficial effects on breast cancer, it clearly acts as an estrogen agonist in the endometrium, leading to an increased rate of endometrial carcinoma in women taking tamoxifen under chronic conditions. Moreover, it is most likely that a pure antiestrogen will have beneficial effects superior to those of tamoxifen in breast cancer prevention and treatment. 

Tantivejkul, K., Vucenik, I., Eiseman, J., and Shamsuddin, A.M., 2003, Inositol hexaphosphate (IP6) enhances the anti-proliferative effects of adriamycin and tamoxifen in breast cancer. Breast Cancer Res. Treat. 79 301-312. 

Lawrence, J.A., Adamson, P.C., Caruso, R., Chow, C., Kleiner, D., Murphy, R.F., Venzon, D.J., Shovlin, M., Noone, M., Merino, M., Cowan, K.H., Kaiser, M., O Shaughnessy, J. and Zujewski, J. (2001) Phase I clinical trial of alitretinoin and tamoxifen in breast cancer patients toxicity, pharmacokinetic, and biomarker evaluations. Journal of Clinical Oncology, 19, 2754-2763. 

Ciocca D.R., Elledge R., 2000, Molecular markers for predicting response to tamoxifen in breast cancer patients. Endocrine 13 1-10. 

Berry D (2013) CYP2D6 genotyping and the use of tamoxifen in breast cancer. J Natl Cancer Inst 105 1267-1269... 

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