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