Post on 25-Dec-2015
Jo Anne Zujewski, MDCenter for Global Health
National Cancer Institute, U.S.A.Dar es Salaam
September 11, 2014
Breast Cancer Risk Factors and Prevention
\
CANCER CONTROL StrategiesDisease-Based approach
EARLYDETECTION
DIAGNOSIS
TREATMENT
PRIMARYPREVENTION
Risk Factors
Breast Cancer
Hormonal factors
Genetic factors
Environmental factors
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
Breast Cancer Incidence by Age
SEER 1973-2000
Jordan
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
Modifiable Risk Factors
Risk Factor High Risk Category
Referent Group
Relative Risk
Obesity > 35 BMI < 25 1.2-1.5
Hormone Replacement
>5 years none 1.26
Breast Feeding none Breast feed > 1 year
Physical Activity Inactive Regular activity
1.25-1.7
Alcohol Use >2 drinks/day Non drinkers 1.5
McTiernan, Oncologist 2003
Hamijima, Br J Ca 2002
Ways to decease breast cancerPRIMARY PREVENTION
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
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 = 10,739YES
NO
Placebo
Placebo
*
* Initially: CE only (N =331), CE+MPA, or placeboWHI Writing Group. JAMA 2002;288:321-333.
Chlebowski JAMA 2003;289:3243-3253 Chlebowski et al. JAMA 289:3243, 2003
Hysterectomy
• Lifestyle- all women
• Medical Prevention-high risk women• Anti-hormonal therapy• Prophylactic surgery
Breast Cancer Primary Prevention
• 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
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
Sources of Guidance on Health Behaviors and Cancer
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
Ways to lower breast cancer risk
Breastfeeding your children
• Lifestyle- all women
• Medical Prevention-high risk women• Anti-hormonal therapy• Prophylactic surgery
Breast Cancer Primary Prevention
Breast Cancer Risk Factors
15-20%
5-10%
70-80%
MOST WOMEN WHO develop BREAST CANCER DO NOT HAVE A FAMILY HISTORY
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
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%)
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)
Clinical Management of BRCA Mutation-Positive Patient
Positive BRCA1 or BRCA2 test result
Possible testing for other adult relatives
Increasedsurveillance
Prophylacticsurgery
Lifestyle changes
Prevention (tamoxifen)
Non-modifiable Risk Factors
Risk Factor High Risk Category
Referent Group
Relative Risk
Age > 65 <65 5.8
Family history One 1st degree relative
No family hx 1.4-2.0
Two 1st deg relatives No family hx 4-6
Previous breast pathology
Hyperplasia None 1.9
Atypical hyperplasia None 4.0
Lobular neoplasia None 7-12
DCIS None 4-7
Mammographic density
Dense breast tissue Normal 4-6
Radiation exposure
Thoracic irradiation No exposure 4.5-25
Exogenous Hormones (WHI)
Hazards Ratio (E+P:placebo)
95% CI (adjusted)
Breast ca 1.26 0.83-1.92
Total CVD 1.22 1.00-1.49
Colon ca 0.63 0.32-1.24
Endometrial ca 0.83 0.29-2.32
Total fractures 0.76 0.63-0.92
Roussouw, JAMA, 2002
N=16,608 women 50-79 years old
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
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
Thank you