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Breast Cancer Treatment : Aromatase Inhibitors vs. Tamoxifen

Breast Cancer Treatment : Aromatase Inhibitors vs. Tamoxifen . Elizabeth Geddes March 9, 2006 Advisor - Dr. Hadley. Breast Cancer Brief. Breast cancer is the MOST common cancer in women 2 nd leading cause of cancer deaths in women

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Breast Cancer Treatment : Aromatase Inhibitors vs. Tamoxifen

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  1. Breast Cancer Treatment : Aromatase Inhibitors vs. Tamoxifen Elizabeth Geddes March 9, 2006 Advisor - Dr. Hadley

  2. Breast Cancer Brief • Breast cancer is the MOST common cancer in women • 2nd leading cause of cancer deaths in women • Over 212,000 women will be diagnosed with breast cancer and over 40,000 will die in 2006

  3. Types of Cancer • Ductal vs. Lobular • Lobular – can be in lobes or lobules • In Situ vs. Invasive • Ductal Invasive is most common • Hormone receptor positive or negative • Estrogen receptor / Progesterone receptor • Hormone receptor positive cancers are dependent on estrogen/progesterone for growth

  4. Treatment Options • Chemotherapy • Radiation • Mastectomy • Lumpectomy • Alternative Medicine • HORMONE THERAPY

  5. Hormone Therapy • Hormone therapy is effective in hormone receptor positive tumors • 75% of all breast cancers are receptor positive • Treatment is non-invasive, fairly non-toxic • Used to inhibit progression or recurrence of disease

  6. Tamoxifen • Selective estrogen receptor modulator • Estrogen agonist and antagonist • Reversibly blocks estrogen binding to receptor in tumor cells • Agonist effects include decreased blood lipid changes, and increased bone density

  7. Adverse Effects • Thromboembolic events • Endometrial cancer • Hepatic carcinomas • Menstrual dysregularities • Vaginal dryness and bleeding • Hot flushes

  8. Tamoxifen Resistance • Tamoxifen has only been proven effective for a maximum of 5 years • The risks are greater than the benefits past this time frame • Resistance of the tumors is attributed to this decrease in efficacy • Resistance is thought to be due to the tumor becoming estrogen independent

  9. Aromatase Inhibitors • Block aromatase, inhibiting estrogen synthesis • Steroidal • Exemestane • Irreversibly inhibit • Non-Steroidal • Anastrozole and Letrozole • Reversibly inhibit

  10. Aromatase Inhibitors • Only useful in postmenopausal women • Production of estrogen in premenopausal women overrides aromatase inhibitors

  11. Adverse Effects • Osteoporosis • Thromboembolic Events • Cardiac Events • Vaginal dryness

  12. Clinical TrialsAromatase Inhibitors vs. Tamoxifen • ATAC trial • 68 months follow-up there was improved disease free survival with Anastrozole over Tamoxifen • Big 1-98 • 25.8 months follow-up there was improved disease free survival with Letrozole over Tamoxifen

  13. Sequential Treatments • It has been proven that there is an increased disease free survival after 5 years of therapy in patients who switched to aromatase inhibitors after 2-3 years of Tamoxifen compared to those who remained on Tamoxifen • ABSCG/ARNO - Anastrozole • ITA - Anastrozole • IES – Exemestane

  14. Long term treatments • Early results of the MA.17 clinical trial show promise for aromatase inhibitor effectiveness after 5 years of treatment • Increased disease free survival in patients continuing treatments compared to those on no treatment • Letrozole has shown positive effect in overall survival

  15. Current Debates • Aromatase inhibitors as initial treatment versus post-Tamoxifen treatment • How many years of Tamoxifen before beginning aromatase inhibitors? • Effective length of treatment with aromatase inhibitors • Efficacy between different aromatase inhibitors

  16. Tolerability • In ATAC trial fewer patients withdrew and there were less reported side effects in the aromatase inhibitor population

  17. Why should a primary care PA care? • Some of our patients will be diagnosed with breast cancer • Patients will follow-up with PCP after seeing oncologist • We need to be aware of these drugs • When to use them • Which is the best option for our patient • Adverse Effects • Be knowledgeable for patient education

  18. Conclusion • Tamoxifen was gold standard • Aromatase inhibitors are proving to be more effective • Increased disease free survival • Longer treatment options • Better tolerability • Several questions remain unanswered • Hormonal therapies are effective in halting the progression and recurrence of breast cancer

  19. References • Abram, P., Maass, N., Rea, D., Simon, S., Steger, G. Case studies of fulvestrant (‘Faslodex’) in postmenopausal women with advanced breast cancer. Cancer Treatment Reviews 2005; 31: S17-S25. • Benson, J.R. The use of aromatase inhibitors in postmenopausal women with hormone receptor positive breast cancer. J Clin Oncol 2005; 23: 6807-6809 • Breastcancer.org. January 2006. Available at www.breastcancer.org. Accessed November 2005. • Brennan, M., Wilcken, N., French, J., Ung, O., Boyages, J. Management of early breast • cancer—the current approach. Aust Fam Physician 2005; 34: 755-60. • de Ziegler, D., Mattenberger, C., Luyet, C., Romoscanu, I., Irion, N., Bianchi-Demicheli, • F. Clinical use of aromatase inhibitors in premenopausal women. J Steroid Biochem Mol Biol 2005; 95: 121-127. • Gould, R., Garcia, A. Update on aromatase inhibitors in breast cancer. Curr Opin Obstet Gynecol • 2006; 18: 41-46. • Howell, A. Selective oestrogen receptor modulators, aromatase inhibitors and the female • breast. Curr Opin Obstet Gynecol 2005; 17: 429-434. • Ingle, J.N., Suman, V.J. Aromatase inhibitors for therapy of advanced breast cancer. J • Steroid Biochem Mol Biol 2005; 95: 113-119. • Jonat, W., Hilpert, F. Optimizing the use of aromatase inhibitors in adjuvant therapy for • postmenopausal patients with hormone-responsive early breast cancer: current and future prospects. J Cancer Res Clin Oncol 2006; 1: 1-13. • Kaufmann, M., Rody, A. Long-term risk of breast cancer recurrence: the need for • extended adjuvant therapy. J Cancer Res Clin Oncol 2005; 131: 487-494. • Miller, W.R., Anderson, T.J., White, S., Larionov, A., Murray, J., Evans, D., et al. • Aromatase inhibitors: cellular and molecular effects. J Steroid Biochem • Mol Biol 2005; 95: 83-89. • Normanno, N., DiMaio, M., DeMaio, E., DeLuca, A., deMatteis, A., Giordano, A., et al. • Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocrine-Related Cancer 2005; 12: 721-747. • Osborne, C.K., Schiff, R. Aromatase inhibitors: future directions. J Steroid Biochem Mol • Biol 2005; 95: 183-187. • Sismondi, P., Biglia, N., Giai, M., Sgro, L., Campagnoli, C. Metabolic effects of • tamoxifen in postmenopause. Anticancer Res 1994; 14: 2237-2244. • Young, J.L, Fritz, A., Gonghua, L., Thoburn, K., Kres, J., Roffers, S. Breast cancer. September 2005. Available at http://training.seer.cancer.gov/ss_module01_breast/00_bc_home.html. Accessed February 2006.

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