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Breast Cancer Prevention Art or Science?
Kristi McIntyre M.D.
Texas Oncology
2005
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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.%
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You Choose:
• Start Raloxifene
• Start Tamoxifen
• Wait several months and reassess
• Clinical trial
• No therapy but observation and surveillance
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Breast Cancer Risk FactorsBreast Cancer Risk Factors
image library - Table 94-01.jpg.url
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Breast Cancer Incidence
image library - f094-01.jpg.url
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How much of Breast cancer is Hereditary?
Hereditary
Sporadic
5-7%
15-20%
Familial clusters
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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
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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
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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
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Benign Breast Disease
Nonproliferative 1 Proliferative ,no atypia 2X Atypical Hyperplasia 4XIn Situ 10-20X
Histology RR
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ASCO 2005 Cuzick L
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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)
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Chemoprevention of breast cancer
Can we find an ideal agent?
Who should take it?
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Mechanism of Disease: Estrogen Carcinogenesis; Yager et al NEJMJan 2006
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Smith, I. E. et al. N Engl J Med 2003;348:2431-2442
Mechanism of action of Tamoxifen
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NSABP B-24 TRIALNSABP B-24 TRIAL
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NSABP P-1
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*50% reduction
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Dvt.gif
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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
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Multiple Outcomes Raloxifene Evaluations Study
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Multiple Outcomes Raloxifene Evaluation TRIAL
Breast cancer risk reduction :76%
Raloxifene
Placebo
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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
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Smith, I. E. et al. N Engl J Med 2003;348:2431-2442
Aromatase Inhibitors
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Smith, I. E. et al. N Engl J Med 2003;348:2431-2442
Classification of Aromatase Inhibitors
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Aromatase Inhibitor adjuvant trials and contralateral breast cancer incidence
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Aromatase Inhibitors : Adverse effects compared to Tamoxifen
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Aromatase Inhibitor Prevention Trials
IBIS -IIMAP - 3
Arimidex
Placebo Exemestane
placebo
6,000 postmenopausal women5000 postmenopausal women
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2Tamoxifen
Raloxifene
?
Aromatase InhibitorNSABP P-4NSABP P-4
Future Breast cancer Prevention trial
Future Breast cancer Prevention trial
Spring 06
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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