Breast Cancer Prevention and
Risk Reduction
Julie R. Gralow, M.D.
Director, Breast Medical Oncology, Seattle Cancer Care Alliance
Professor, Medical Oncology, University of Washington School of
Medicine
Member, Clinical Division, Fred Hutchinson Cancer Research Center
Breast Cancer Prevention and
Risk Reduction
• Primary Prevention
–Lifestyle
–Chemoprevention
–Prophylactic surgery
• Secondary Prevention
–Screening and early detection
Breast Cancer Risk Reduction:
Lifestyle
Exercise
Diet
Weight
Alcohol
Lifestyle Recommendations for
Breast Cancer Risk Reduction
• Regular exercise
• Low fat, high fiber diet
• Good intake of fruits and
vegetables
• Low alcohol
• Maintain a good body weight
Report of the President’s Cancer Panel 2006-2007
Healthy Lifestyles
www.deainfo.nih.nci.gov/advisory/pcp
• Tobacco and second hand tobacco smoke exposure
account for 1/3 of cancer deaths in the U.S.
• Unhealthy diet, weight, physical activity may
account for another 1/3
• Clear evidence that healthy lifestyle behaviors can
reduce chance of developing cancer
Exercise and Breast Cancer
Risk
• Regular physical activity is associated
with decreased breast cancer risk
• Many studies have found that women
who exercise at higher intensity levels
for > 3 hours/week reduce their risk of
breast cancer by 20-40%
Women’s Health Initiative (WHI) Cohort:
Physical Activity and Breast Cancer Risk
McTiernan A et al, JAMA 2003
• Patients: 74,171 women ages 50-79
• Study: incidence of breast cancer correlated to physical
activity
• Results:
– 1,780 cases of breast cancer over 4.7 yrs
– Regular physical activity at age 18, 35, and 50 had
14% reduction in breast cancer risk
– 1.25-2.5 hrs/week brisk walking had 18% decreased
risk
– Greatest reduction seen for women with >10
hrs/week brisk walking
Obesity and Cancer
• 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
Breast Cancer Prevention and
Risk Reduction
• Primary Prevention
–Lifestyle
–Chemoprevention
–Prophylactic surgery
• Secondary Prevention
–Screening and early detection
Chemoprevention
The use of natural or synthetic chemical
agents to reverse, suppress, or prevent
cancer
Breast Cancer Chemoprevention
Agents
• FDA approved for breast cancer chemoprevention:
– Tamoxifen (Nolvadex)
– Raloxifene (Evista)
• Both drugs are synthetic, non-steroidal, Selective
Estrogen Receptor Modulators (SERMs)
– Mixed anti-estrogenic and weak estrogenic
effects depending on the tissue
NSABP P-01 Tamoxifen Breast
Cancer Prevention Trial
Fisher B et al, JNCI 90:1371-1378, 1998
•13,400 women at
high risk for breast
cancer
•Randomized to
placebo vs.
tamoxifen for 5
years
•Study stopped at
mean 3.5 years of
follow-up)
5-Year Non-Breast Cancer Events
on Tamoxifen (10,000 Women)
Gail M et al, JNCI 1999
Age Group (Caucasian)
Event
35-39 40-49 50-59 60-69 70-79
Hip fracture
-1
-1
-22
-52
-151
Endometrial CA +2
+16
+120 +206
+223
CVA
+2
+13
+32
+91
+196
PE
+7
+15
+49
+85
+177
DVT
+13
+15
+16
+28
+44
Colle’s/Spine Fx -13
-13
-42
-71
-115
Cataracts
+35
+35
+101 +269
+384
Quality of life (hot flashes, vaginal discharge) must be
factored in as well
NSABP P-02
STAR Chemoprevention Trial
(Study of Tamoxifen and Raloxifene)
Wickerham DL et al, ASCO 2006, abstract 5
•19,747
postmenopausal
women at risk for
breast cancer (5-year
risk 1.7%)
•Randomized to
tamoxifen vs.
raloxifene for 5 years
•47 month median
follow-up
•Concern about
implications of
difference in DCIS
Tamoxifen and Raloxifene for
Breast Cancer Chemoprevention
Weighing the Risks and Benefits
• Both provide women at increased risk with an
option to reduce their chance of developing
breast cancer
• Influences on mortality and long-term risks
and benefits have not been defined in the
prevention setting
• Balance of benefits and risks varies by age,
breast cancer risk (and hysterectomy status
for tamoxifen)
Breast Cancer Chemoprevention:
Ongoing Studies
• Postmenopausal
– Aromatase inhibitors
» IBIS 2 (Anastrozole vs. Placebo)
» EXCEL (Exemestane vs Placebo)
• Premenopausal
– Ovarian suppression
– Vitamin D
Breast Cancer Prevention and
Risk Reduction
• Primary Prevention
–Lifestyle
–Chemoprevention
–Prophylactic surgery
• Secondary Prevention
–Screening and early detection
Breast Cancer Risk Reduction:
Prophylactic Surgery
Prophylactic mastectomy and
oophorectomy should be considered
only for women at substantial risk
Considerations for Women with
Inherited Susceptibility to Breast and
Ovarian Cancer
• Prophylactic Mastectomy
– Reduces breast cancer risk by 90%
– Rare breast cancers still occur
– Disfiguring
– An option for women at very high risk
Long-term
Satisfaction and Psychological
and Social Function Following Bilateral
Prophylactic Mastectomy
• Reduced level of concern
about developing breast
cancer (74%)
• Some patients reported
negative impact on:
– Emotional stability (9%)
– Level of stress (14%)
– Self-esteem (18%)
– Sexual relationships (23%)
– Feelings of femininity
(25%)
– Body image (36%)
Frost MH et al. JAMA 2000;284:319-24.
Considerations for Women with
Inherited Susceptibility to Breast and
Ovarian Cancer
• Prophylactic Oophorectomy
– Reduces ovarian cancer risk by 90-95%
– Peritoneal carcinomatosis may still occur
– Induces surgical menopause
– Reduces breast cancer risk by up to 50%
– Recommended for BRCA1/2 mutation carriers
after childbearing
Breast Cancer Prevention and
Risk Reduction
• Primary Prevention
–Lifestyle
–Chemoprevention
–Prophylactic surgery
• Secondary Prevention
–Screening and early detection
Breast Cancer Risk Reduction
Breast Cancer Screening
(Secondary Prevention)
Early Detection of Breast Cancer:
The Controversy Around Breast Imaging
Mammogram
Ultrasound
• Magnetic
Resonance
Imaging (MRI)
American Cancer Society
Recommendations for Breast
Cancer Screening 2010
• Mammography: Annually beginning at age 40
and continuing as long as the woman is in
good health
• Health Professional’s Exam: About every 3
years between 20-39, then annually
• Self-Exam: An option for women beginning at
about age 20
• MRI: Women at high risk (> 20% lifetime)
should get a mammogram and MRI yearly.
Women at moderately increased risk (15-20%)
should talk with their health care providers
about MRI screening.
Screening Recommendations for
Women with Inherited Susceptibility
for Breast Cancer
• Breast Cancer Surveillance
– Monthly breast self-exams (begin by age 18)
– Clinical breast exam every 6 months
– Annual mammography (beginning age 25)
– Consider annual MRI
• Ovarian Cancer Surveillance
– Annually or semi-annually beginning at 25-35:
– Pelvic examination
– Transvaginal ultrasound
– Serum CA-125
Early Detection
Imaging in High Risk Individuals
Sensitivity
Specificity
Mammogram
33-40%
93-99.8%
Breast MRI
77-91%
81-97%
Breast MRI is better at detecting cancer than
mammogram in high risk women, but has a
higher rate of “false positives” e.g. biopsy of benign lesions
Kriege M et al. NEJM 2004;351:427-37
Warner E et al. JAMA 2004;292:1317-25
Kuhl CK et al. JCO 2005;8469-76.
Leach MO et al. Lancet 2005;365:1769-78
Breast Cancer Prevention
Strategies in Low- and MiddleIncome Countries
• Public awareness and education
• Health Professional education and training
• Individualized approaches based on patient risk
Breast Health Global Initiative (BHGI)
Early Detection Strategies in Low- and
Middle-Income Countries
Yip C et al, Cancer Suppl 113, 2008
• Basic level
– Clinic visits for breast problems (history and exam)
– Train health care providers in clinical breast exam (CBE)
• Limited level
– Targeted educational outreach encouraging women to
seek attention for breast problems
» Link to general health/women’s health programs
– Screening clinical breast exams for higher risk
– Diagnostic imaging (mammogram and ultrasound) for
breast problems
– ?Screening mammogram for select targeted group
Breast Health Global Initiative (BHGI)
Early Detection Strategies in Low- and
Middle-Income Countries
Yip C et al, Cancer Suppl 113, 2008
• Enhanced level
– Regional awareness programs on breast health
– Screening
» Mammography where resources sufficient
» Every 2 years ages 50-69?
» Every 12-18 months ages 40-49
– Image-guided biopsy
• Maximal level
– National awareness campaigns
– Annual screening mammography in women > 40
– Consider other imaging technology in women at high
risk - Breast MRI
American Cancer Society:
Major Risk Factors for Breast Cancer Over
Which Women Have Some Control
• Exercise: Women can lower their risk of breast
cancer by exercising vigorously for 45-60
minutes on 5 or more days per week.
Postmenopausal women can lower their risk with
any level of physical activity performed on a
regular basis.
• Weight: Obesity increases a woman’s risk of
postmenopsaul (but not premenopausal) breast
cancer, as does weight gain during adulthood
• Alcohol use: Women who drink just 2 alcoholic
beverages a day face a 21% increase in their risk
for breast cancer