Breast Cancer Treatment Aromatase Inhibitors vs Tamoxifen Elizabeth

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 Over 212, 000 women will be diagnosed with breast cancer and over 40, 000 will die in 2006

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

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

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

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

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

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

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

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

Adverse Effects • • Osteoporosis Thromboembolic Events Cardiac Events Vaginal dryness

Clinical Trials Aromatase 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

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

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

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

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

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

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

References • • • • • • • Abram, P. , Maass, ’) in postmenopausal Maass, N. , Rea, D. , Simon, S. , Steger, G. Case studies of fulvestrant (‘Faslodex’) women with advanced breast cancer. Cancer Treatment Reviews 2005; 31: S 17 -S 25. 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. , Di. Maio, M. , De. Maio, E. , De. Luca, A. , de. Matteis, 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_module 01_breast/00_bc_home. html. Accessed February 2006.