1. Christina Laukaitis, MD, PhD, FACP 22 June 2012

2. * To continue to increase the competitive stance of cancer research and training at Northern Arizona University by adding new cancer researchers and by continuing strong faculty development programs for all junior faculty. * To develop programs that facilitate the successful transition of Native American students into the universities and that enhance the retention and graduation of Native Americans undergraduates in biomedical sciences. * To develop sustainable community education programs and research for cancer prevention that meet the unique needs of the Hopi Tribe and the Navajo and Tohono O’odham Nations.

3. * Analysis of the roles of genes and chromosome rearrangements in genomic instability * Uranium as environmental risk factor for cancer among the Navajo * Allostery, protein complexes and cellular distribution for the Nitric Oxide Receptor & soluble Guanylyl Cyclase

4. * Focused on transitioning Native American students into undergraduate work at Partnership institutions and preparing them to enter graduate programs in biomedical sciences through a research-based training program * Summer research program * NAU or UA * Stipend & mentoring provided

5. 153 Participating students 106 American Indian 13 Science & healthcare 10 Grad school

6. * Developing a continuing education curriculum for community healthcare workers * Identifying resource and educational needs of healthcare providers, and partnering to fill those needs * In collaboration with IHS, a ‘virtual’ colon cancer screening program has been created in remote areas of the Navajo Nation

7. Cancer Risk Exam & Test Results Symptoms Family History Medical History Habits

8. At-risk personPerson with cancer Family history/genetics Behaviors (e.g. smoking) Exposures (e.g. uranium, HPV) Medical issues (e.g. diabetes, obesity, previous cancer) Intervention

9. * Choose an appropriate group to study * Elevated baseline risk * Develop an appropriate intervention * Likely to change physiology of disease * Side effect minimal/tolerable * Intervene at the right time * Before pre-cancerous changes are irreversible * Follow up for an appropriate time-period

10. * Breast cancer prevention * 16,000 women at high-risk of breast cancer * ½ treated with placebo, ½ with tamoxifen * After 5 years, breast cancer rates were ½ for those treated with tamoxifen versus placebo Cumulative number of cases (per 1000 women) Placebo Tamoxifen 0 1 2 3 4 5 6 40 30 20 10 0 Invasive breast cancer rates in women at high risk Years

11. Tamoxifen (BCPT)Raloxifene (STAR) Invasive breast cancer risk reduction ~45%Similar to tamoxifen LCIS/DCIS risk reduction~50%None Thrombotic events3x increase29% less than tamoxifen Uterine cancer risk2-3x increaseSlightly less than tamoxifen Fisher et al., JNCI 2005 Vogel et al., JAMA 2006

12. Bad effects Increases uterine cancer risk Increases blood clot risk Tamoxifen Good effects Reduces breast cancer risk Lowers LDL cholesterol Strengthens bones Kleinsmith et al. NCI 2002

13. Raloxifene Bad effects No relief for hot flashes  No reduction of LCIS  No reduction of DCIS Good effects Lowers LDL cholesterol Reduces risk for invasive breast cancer Strengthens bones  Fewer uterine cancers than tamoxifen  Fewer blood clots than tamoxifen Kleinsmith et al. NCI 2002

14. * Behavioral interventions for risk factors * Nutritional supplements * Vaccinations against infectious cancer causes * Medications for people at high-risk * Eliminating pre-cancerous cells * Intensive screening to identify cancer early

15. * Test whether intervention reduces cancer rates * Inherently difficult * Measuring something that DOESN’T happen * May be many years before see effects * Difficult to determine cause v. chance

16. * I didn’t have an accident today ;) * June in Tucson v. January in Flagstaff

17. 1.1. Does the woman have a medical history of any breast cancer or of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS)?ductal carcinoma in situ (DCIS)lobular carcinoma in situ (LCIS) 2.2.What is the woman's age? 3.3.What was the woman's age at the time of her first menstrual period?menstrual period 4.4.What was the woman's age at the time of her first live birth of a child? 5.5. How many of the woman's first-degree relatives - mother, sisters, daughters - have had breast cancer? 6.6.Has the woman ever had a breast biopsy?biopsy 6a6a.How many breast biopsies (positive or negative) has the woman had? 6b6b.Has the woman had at least one breast biopsy with atypical hyperplasia?atypical hyperplasia 7.7.What is the woman's race/ethnicity? Gail et al., JNCI 1989

18. * Average risk * ~12% lifetime risk * 1/8 women will develop breast cancer in her life * Moderate risk * <5x average risk * 15-25% lifetime * 1 first-degree relative >60, obese, alcohol use, etc. * High risk * 5-10x average risk * Lifetime risk >25% by Claus & >50% by Gail models * LCIS, ADH, ALH; 2 first-degree relatives, or 1 <60 * Very high risk * >10x average risk * >50% lifetime risk * BRCA1 or BRCA2 mutation or other syndrome Schwartz et al., The Breast J 2007 Schwartz et al., Cancer 2007 Zakhireh et al., Eur J Cancer 2008

19. * Breast cancer prevention * Vitamin D * Deficient pre-menopausal women with elevated baseline risk * Outcome: breast density * Broccoli extract * Post-menopausal women with elevated risk on tamoxifen * Outcomes: breast density & tamoxifen tolerability * Letrozole (dose-finding Phase I trial) * Post-menopausal women with elevated breast cancer risk * Outcomes: side effects & pathology on random fine needle aspirate

20. * Lifestyle modification * Intensive screening * Chemoprevention * Prophylactic surgery Risk Benefit Potential Risk Potential Benefit