1. By: Erin Hutzell

2. Background: Breast Cancer Second leading cause of death due to cancer among women in 2007 1 in 3 women diagnosed with cancer is diagnosed with breast cancer Risk Factors Environmental Genetic

3. Background: Breast Cancer Invasive VS. Noninvasive Estrogen Receptor (ER) positive VS. Estrogen Receptor negative Mechanism causing breast cancer

4. Background: Chemoprevention and Drugs Chemoprevention What is it? Tamoxifen Selective Estrogen Receptor Modulator (SERM) Raloxifene SERM Exemestane Aromatase Inhibitor (AI)

5. Questions How effective is each drug in preventing breast cancer? What are the side-effects of each drug treatment? Which drug is the best possible chemopreventative measure for breast cancer?

6. Tamoxifen * Modified from Grese et al 1997

7. Tamoxifen NSABP P-1 Study by Fisher et al (1998) Subject Criteria 60 years + 35-59 years with predicted breast cancer risk History of lobular carcinoma in situ or atypical hyperplasia Methods Control group Tamoxifen group

8. Tamoxifen Supported By: IBIS-I Study (Cuzick et al 2002) Meta-analysis by Cuzick et al Not Supported By: Royal Marsden (Powles et al 1998) Italian Tamoxifen Prevention Study (Veronesi et al 1998) Top: Fisher et al. 1998 Bottom: Fisher et al. 2005 * Kramer et al. 2004

9. Tamoxifen NSABP P-1 (Fisher et al 1998 and 2005) Osteoporotic Fractures: REDUCED Invasive Endometrial Cancer: RISK INCREASED Supported by IBIS-I (Cuzick et al 2002) and Royal Marsden (Powles et al 1998) Thromboembolic Events: RISK INCREASED Supported by IBIS-I, Royal Marsden, and Italian Tamoxifen Prevention Study (Veronesi et al 1998) Conclusion: Tamoxifen is an effective drug but has adverse side-effects * Kramer et al. 2004

10. Raloxifene * Structures of Tamoxifen and Raloxifene highlighting structural differences from Grese et al 1997

11. Raloxifene Continuing Outcomes Relevant to Evista (CORE) trial by Martino et al (2004) Subject Criteria Postmenopausal women with osteoporosis from an earlier trial (MORE trial) Methods Raloxifene group Placebo group

12. Raloxifene * Martino et al. 2004 * Table modified from Nelson et al. 2013 that compares the effectiveness of Tamoxifen and Raloxifene

13. Raloxifene * Table of the combined results of the primary prevention trials of Raloxifene and Tamoxifen demonstrating side-effects (modified from Nelson et al. 2013)

14. Exemestane http://pubchem.ncbi.nlm.nih.gov/summ ary/summary.cgi?cid=60198

15. Exemestane Mammary Prevention.3 (MAP3) Trial by Goss et al (2011) Subject Criteria Postmenopausal Women At least one risk factor Methods Exemestane Placebo

16. Exemestane Conclusion: Exemestane is a more effective chemopreventative than Tamoxifen Supported by: Intergroup Exemestane Study by Bliss et al (2012) Exemestane produced better disease-free survival Drug RegimenRisk Reduction Tamoxifen (20 mg daily for 5 years) 43% Exemestane (25 mg daily for 3 years) 65% Comparison of the risk reductions for Tamoxifen and Exemestane Table modified from Zhang et al. 2012 * Goss et al 2011

17. Exemestane Drug Regimen Effect on Bone Common Adverse Effects Serious But Rare Adverse Events Indicated Population Exemestane (25 mg daily for 3 years) UnfavorableHot flashes, nausea, diarrhea, fatigue, insomnia, joint pain, arthralgia Not identifiedNot FDA approved; postmenopausal women only Tamoxifen (20 mg daily for 5 years) NeutralHot flashes, vaginal discharge, bleeding, altered menses, fluid retention, nausea, vomiting, weight loss, athralgia Endometrial cancer, thromboembolism, stroke, heart attack, cataracts FDA-approved for premenopausal and postmenopausal women with a 5 year risk of ≥1.66% Comparison of the side-effects of Tamoxifen, Raloxifene, and Exemestane Table modified from Zhang et al. 2012

18. Conclusion DrugRisk ReductionSide-Effects TamoxifenLow (43%)Severe Exemestane High (65%)Few/No Severe Exemestane has the potential to be the best possible chemopreventative measure for breast cancer Future: Research Exemestane Explore Medication Combinations Demographics of Patients

19. Bibliography