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Breast Cancer Prevention Art or Science?
Kristi McIntyre M.D.
Texas Oncology
2005
Patient
• 59 year old healthy Caucasian postmenopausal female with recent abnormal screening mammogram . She is asymptomatic.
• No family history of breast cancer
• Uses deodorant
• No significant health issues ; normal bone density
• Has chronic sinusitis and takes antimicrobials frequently
• Biopsy of breast shows atypical ductal hyperplasia
• Gail risk 3.5.%
You Choose:
• Start Raloxifene
• Start Tamoxifen
• Wait several months and reassess
• Clinical trial
• No therapy but observation and surveillance
Breast Cancer Risk FactorsBreast Cancer Risk Factors
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Breast Cancer Incidence
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How much of Breast cancer is Hereditary?
Hereditary
Sporadic
5-7%
15-20%
Familial clusters
Family history and breast cancer riskFamily history and breast cancer risk
Most hereditary breast cancers arise from mutations in BRCA1 and BRCA2
Autosomal dominant , tumor suppressor gene
•Age breast cancer <50•Bilaterality•Male breast cancer• ovarian cancer•Multiple other cancers
Ashkenazi Jews
Reproductive Factors and Breast CancerReproductive Factors and Breast Cancer
Menarche Menarche MenopauseMenopause
Menarche <15 OR 1.2Menopause >50 OR 1.5Null parity OR 2.0Breastfeeding 4.3% decrease risk/yrFirst live birth<20 OR 0.5First live birth >30 OR 1.5Postmenopausal Estradiol levels
WHI Trial of Estrogen plus Progestin
E+P placebo p-value
Invasive Breast cancers 199 150 0.003
Abnormal Mammograms 716 395 0.0001
SEER high stage 25% 16% 0.041
More breast cancers diagnosed at more advanced stage and increased abnormal mammograms
Chlebowski JAMA 2003;289. 3243
Benign Breast Disease
Nonproliferative 1 Proliferative ,no atypia 2X Atypical Hyperplasia 4XIn Situ 10-20X
Histology RR
ASCO 2005 Cuzick L
Lifestyle factors and breast cancer risk
• Body mass index: postmenopausal women >30% excess BMI increased risk
• Dietary fat intake: increased risk• NSAID use: decreases risk • Physical activity: 1.25 to 2.5/hrs week brisk
walking had 18 % decrease risk• Alcohol use: increased (dose dependent)
Chemoprevention of breast cancer
Can we find an ideal agent?
Who should take it?
Mechanism of Disease: Estrogen Carcinogenesis; Yager et al NEJMJan 2006
Smith, I. E. et al. N Engl J Med 2003;348:2431-2442
Mechanism of action of Tamoxifen
NSABP B-24 TRIALNSABP B-24 TRIAL
NSABP P-1
*50% reduction
Dvt.gif
BCPT results: bone and endometrial cancer events
0
20
40
60
80
100
120
140
bone0
2
4
6
8
10
12
14
uterine ca
Bone fractures Endometrial cancers
5.4
13
111
137
placebo
Tamoxifen
Multiple Outcomes Raloxifene Evaluations Study
Multiple Outcomes Raloxifene Evaluation TRIAL
Breast cancer risk reduction :76%
Raloxifene
Placebo
STAR trial objectives
Evaluate the effect of Tamoxifen vs. Raloxifene in reducing the incidence of:
Invasive breast cancer•Noninvasive breast cancer•Endometrial cancer•Vascular events•Bone fractures
Smith, I. E. et al. N Engl J Med 2003;348:2431-2442
Aromatase Inhibitors
Smith, I. E. et al. N Engl J Med 2003;348:2431-2442
Classification of Aromatase Inhibitors
Aromatase Inhibitor adjuvant trials and contralateral breast cancer incidence
Aromatase Inhibitors : Adverse effects compared to Tamoxifen
Aromatase Inhibitor Prevention Trials
IBIS -IIMAP - 3
Arimidex
Placebo Exemestane
placebo
6,000 postmenopausal women5000 postmenopausal women
2Tamoxifen
Raloxifene
?
Aromatase InhibitorNSABP P-4NSABP P-4
Future Breast cancer Prevention trial
Future Breast cancer Prevention trial
Spring 06
Conclusions
• Chemoprevention will have a tremendous impact on breast cancer incidence
• Refining criteria of “high risk patient” and measurable surrogate markers
• LOOK FOR RESULTS STAR trial
• Encourage clinical trial participation P-4