1. Jo Anne Zujewski, MD Center for Global Health National Cancer Institute, U.S.A. Dar es Salaam September 11, 2014 Breast Cancer Risk Factors and Prevention \

2. CANCER CONTROL Strategies Disease-Based approach EARLYDETECTION DIAGNOSIS TREATMENT PRIMARYPREVENTION

3. Risk Factors

4. Risk Factors-not modifiable Gender-female sex Age-older age Family history (and genetics) –Inherited genes account for 5-10% of all breast cancers –MOST women diagnosed with breast cancer do not have a family history of breast cancer Personal history of breast cancer

5. Breast Cancer Incidence by Age SEER 1973-2000 Jordan

6. Breast Cancer Risks Hormonal factors Not (usually) modifiable Reproductive factors No children or older age of first birth Menses age 11 or younger Menopause age 55 or older Modifiable Breast Feeding Hormonal therapies

7. Modifiable Risk Factors Risk FactorHigh Risk Category Referent GroupRelative Risk Obesity> 35 BMI< 251.2-1.5 Hormone Replacement >5 yearsnone1.26 Breast FeedingnoneBreast feed > 1 year Physical ActivityInactiveRegular activity1.25-1.7 Alcohol Use>2 drinks/dayNon drinkers1.5 McTiernan, Oncologist 2003 Hamijima, Br J Ca 2002

8. Ways to decease breast cancer PRIMARY PREVENTION Health behaviors associated Health behaviors associated with reduced breast cancer risk 1.Prolonged lactation 2.Regular physical activity 3.Weight control 4.Avoid excess alcohol intake 5.Avoid prolonged use of exogenous hormones 6.Avoid excessive radiation exposure McTiernan, et al, Cancer, 113:2325, 2008

9. Hormone Study Design CE (conjugated estrogens) 0.625 mg/d CE 0.625 mg/d + medroxyprogesterone acetate (MPA) 2.5 mg/d N = 16,608 N = 10,739 YES NO Placebo * * Initially: CE only (N =331), CE+MPA, or placebo WHI Writing Group. JAMA 2002;288:321-333. Chlebowski JAMA 2003;289:3243-3253 Chlebowski et al. JAMA 289:3243, 2003 Hysterectomy

10. Lifestyle- all women Medical Prevention-high risk women Anti-hormonal therapy Prophylactic surgery Breast Cancer Primary Prevention

11. Obesity may account for 25- 30% of several major cancers Weight gain during adulthood is a consistent and strong predictor of breast cancer risk Overweight women are 1.3 – 2.1 times more likely to die from breast cancer compared to women with normal weight Obesity and Cancer

12. Breast Cancer Risk Reduction: Lifestyle Exercise –brisk walk for 30 minutes 5 times per week Diet –High in fruits and vegetables –Low in fat and simple carbohydrates Weight control –Body Mass Index < 25 Alcohol –Less than 1 drink per day

13. Sources of Guidance on Health Behaviors and Cancer

14. Br J of Cancer 2002 Alcohol and Breast Cancer Risk (53 studies, N=153,582) g alcohol/day Relative Risk 0 1.0 <5 1.01 15-24 1.13 25-34 1.19 35-44 1.32 >45 1.46 15 grams of alcohol 12 ounces (350 ml) of beer 5 ounces (150) of wine, 3.5 ounces (100 ml) port 1.5 oz. (40 ml) distilled spirits

15. Ways to lower breast cancer risk Breastfeeding your children

16. Lifestyle- all women Medical Prevention-high risk women Anti-hormonal therapy Prophylactic surgery Breast Cancer Primary Prevention

17. Breast Cancer Risk Factors 15-20% 5-10% 70-80% MOST WOMEN WHO develop BREAST CANCER DO NOT HAVE A FAMILY HISTORY

18. Medical Prevention for high risk women “Anti-hormonal” therapies –Consider risks/benefits for women with a greater than 5% chance of developing breast cancer over 5 years Tamoxifen FDA approved for reduction of breast cancer incidence in women at increased risk Raloxifene FDA approved for reduction of breast cancer incidence in post-menopausal women at increased risk Aromatase inhibitors have been studied for breast cancer prevention Preventive Surgery –Consider for women with a greater than 25% lifetime risk of breast cancer Mastectomy Oophorectomy

19. Genes that Cause Hereditary Susceptibility to Breast Cancer BRCA 1/2 –Breast cancer 50 - 85% lifetime risk Early onset, 1/2 diagnosed by age 41 Second primary breast cancer 40 - 60% –Male breast cancer (BRCA2) 6% –Ovarian cancer 10 - 40% –Other cancers slightly increased (colon, uterine, cervix, pancreas, melanoma, prostate) OTHER known genes-rare and uncommon –TP53, PTEN, CHK2 Undiscovered genes (30-70%)

20. Prevention Clinical Trials – Risk Categories Genetic predisposition –Known BRCA1 or BRCA 2 mutation –High probability of mutation (BRCAPRO) Increased risk for breast cancer based on modeling –Gail model –Claus model Previous breast pathology –Atypical ductal hyperplasia –Lobular neoplasia (LCIS) –Ductal carcinoma in situ (DCIS) Breast cancer survivor –Completed therapy > 2 mos ago –+/- hormonal therapy –Contralateral breast cancer risk (1% per year)

21. Clinical Management of BRCA Mutation-Positive Patient Positive BRCA1 or BRCA2 test result Possible testing for other adult relatives IncreasedsurveillanceProphylacticsurgery Lifestyle changes Prevention (tamoxifen)

23. Non-modifiable Risk Factors Risk FactorHigh Risk CategoryReferent Group Relative Risk Age> 65<655.8 Family historyOne 1 st degree relativeNo family hx1.4-2.0 Two 1 st deg relativesNo family hx4-6 Previous breast pathology HyperplasiaNone1.9 Atypical hyperplasiaNone4.0 Lobular neoplasiaNone7-12 DCISNone4-7 Mammographic densityDense breast tissueNormal4-6 Radiation exposureThoracic irradiationNo exposure4.5-25

24. Exogenous Hormones (WHI) Hazards Ratio (E+P:placebo) 95% CI (adjusted) Breast ca1.260.83-1.92 Total CVD1.221.00-1.49 Colon ca0.630.32-1.24 Endometrial ca0.830.29-2.32 Total fractures0.760.63-0.92 Roussouw, JAMA, 2002 N=16,608 women 50-79 years old

25. NOT risk factors ( unknown or inconclusive evidence) Oral contraceptives Ovarian induction Abortions HIV/AIDS Environment –(other than Radiation disasters) Smoking should be avoided for MANY health reasons –But not a known risk for Breast Cancer

26. BREAST CANCER is NOT “ death sentence” Caused by injury to the breast Caught from another person A result of being “be-witched” by an enemy A punishment from God Incurable

27. Thank you