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

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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

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