Breast Cancer Prevention for the Population at Large

Transcription

1 Breast Cancer Prevention for the Population at Large Jack Cuzick Centre for Cancer Prevention Wolfson Institute of Preventive Medicine St Bartholomew s Medical School Queen Mary University of London London, United Kingdom

2 Lymphoma Brain/CNS Bladder Pancreas Endometrial Oesophageal Leukaemia Ovary Stomach Liver Major Cancers UK 2014 Incidence Mortality Lung Breast Colorectal Prostate

3 Two approaches to cancer prevention Simple minimally toxic interventions for all Focussed interventions on high risk groups

4 Relative Risk Whole Population 25% reduction in risk Population Percentile

5 Strategies for Breast Cancer Prevention Life style changes Weight control avoiding obesity Increased physical activity Reduced alcohol consumption Identifying those at highest risk Better Risk Assessment Identifying Precursor Lesions & Biomarkers Identifying suitable preventive agents Repurposing Existing Drugs Progressing Evaluation of New Agents

6 Relative Risks of different cancers by BMI Gallbladder Gastric cardia Pancreas Oesophagus Renal Endometrial Breast (PM) CRC (women) CRC (men) Calle & Kaaks, 2004

7 Weight loss reduces breast cancer incidence Cohort studies Population Weight loss RR Harvie et al ,000 postmenopausal women >5% ~3.5 kg 0.61 ( ) Eliassen et al ,000 postmenopausal women >10kg ~ 15% 0.43 ( ) Prentice et al, ,835 postmenopausal women 2 kg ~3% 0.91 ( ) Teras et al, ,055 overweight & obese postmenopausal women >5 kg ~7% 0.78 ( ) Bariatric surgery

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9 Aspirin low dose ( 100mg/day) for 10 years between ages 50-70y

10 Aspirin: Benefit-Harm Analysis Relative Risks Event Incidence Mortality Colorectal cancer Oesophageal cancer Gastric cancer Lung cancer Prostate cancer Breast cancer Myocardial infarction Stroke Major bleeding GI bleeding Peptic Ulcer Cuzick et al Ann Oncology 2015

11 Estimated Impact of Aspirin on Cancer 7-10% 9-13%

12 Global Incidence of Breast, Colorectal, Lung and Cervix Cancer (Female) Globocan 2012

13 Relative Risk Small Proportion at High Risk 25% reduction in risk 45% % Population Percentile

14 Preventive Therapy Key Ingredients Identification of High-risk women Effective minimally -toxic prophylaxis

15 Better Risk Assessment

16 Some Breast Cancer Risk Models Gail (BCRAT) BCSC with BI-RADs density (Tice et al) BOADICEA Tyrer-Cuzick (IBIS)

17 Risk factors in TC model V7 Age Height Menarche Age first child Age Menopause BMI HRT Family History BRCA testing Proliferative benign breast disease Atypical Hyperplasia LCIS

18 New developments V8 Age Lifestyle Height Menarche Age first child Age Menopause BREAST DENSITY BMI HRT Cysts (aspirated) Family History BRCA testing SNPs Proliferative benign breast disease Atypical Hyperplasia LCIS

19 Tyrer Cuzick Version 8

20 Displaying the Risks

21 Approaches to risk assessment Family history/genetics clinics Needs prior referral Risk assessment by GPs Lack of time and knowledge Risk assessment as part of breast screening Done at first screen age 45-50y Identify high women suitable for preventive therapy Determie risk adapted screening intervals

22 Approaches to Preventive Therapy for Breast Cancer SERMs Tamoxifen Raloxifene Lasofoxifene bbbbarzoxifene

23 IBIS-I study design High Risk Women (N=7,154) Tamoxifen (N=3579) Placebo (N=3575) Median follow-up 16.0 years 5 years Endpoints: Primary: Breast cancer incidence (incl. DCIS) Secondary: Other cancers, BC mortality, all cause mortality, adverse events

24 Cumulative incidence (%) IBIS-I Cumulative incidence for all breast cancer T vs. P HR (95% CI) All 163 vs ( ) Invasive ER+ 100 vs ( ) Placebo Tamoxifen 6.3% 4.6% NNT = Number at risk Placebo Tamoxifen Follow-up time (years)

25 Cumulative incidence (%) IBIS-I Cumulative incidence for all breast cancer T vs. P HR (95% CI) T vs. P HR (95% CI) All 163 vs ( ) All 88 vs ( ) Invasive ER+ 100 vs ( ) Invasive ER+ 60 vs ( ) Placebo Tamoxifen 6.3% 6.3% 4.6% 3.3% Number at risk Placebo Tamoxifen Follow-up time (years)

26 Cumulative incidence (%) IBIS-I Cumulative incidence for all breast cancer T vs. P HR (95% CI) All 251 vs ( ) 12.3% Invasive ER+ 160 vs ( ) Placebo Tamoxifen NNT = % Number at risk Placebo Tamoxifen Follow-up time (years)

27 ALL INVASIVE BREAST CANCERS, 0-10y SERM vs. placebo Tamoxifen vs. placebo Italian Lasofoxifene vs. placebo PEARL 0.25 mg PEARL 0.50 mg Combined NSABP P1 IBIS-I Marsden Raloxifene vs. placebo MORE/CORE RUTH STAR Arzoxifene vs. placebo Hazard ratio Fixed-effect model: -36.2% [-43.0%;-28.7%], p<0.001

28 All ER+ Invasive breast cancers, 0-10y Tamoxifen vs. placebo Italian NSABP P1 IBIS-I Marsden Raloxifene vs. placebo MORE/CORE RUTH STAR Lasofoxifene vs. placebo PEARL 0.25 mg PEARL 0.50 mg SERM vs. placebo Arzoxifene vs. placebo Combined Hazard ratio Fixed-effect model: -49.5% [-56.1%;-41.8%], p<0.001

29 All ER-neg Invasive breast cancers, 0-10y SERM vs. placebo Tamoxifen vs. placebo Italian NSABP P1 IBIS-I Marsden Raloxifene vs. placebo MORE/CORE RUTH STAR Lasofoxifene vs. placebo Arzoxifene vs. placebo Combined Hazard ratio Fixed-effect model: +20.5% [-2.3%;48.6%], p=0.08

30 Approaches to Preventive Therapy for Breast Cancer Aromatase Inhibitors Anastrozole Letrozole Exemestane

31 MAP3 - Cumulative Incidence of Invasive Breast Cancer Goss et al NEJM, 2011

32 IBIS2 - Trial schema Postmenopausal women: Ages Increased risk of breast cancer: Family history Atypia / LCIS Breast density No HRT Anastrozole 1 mg/day (N=1920) N= years Matching placebo (N=1944) FU Ongoing Baseline 6 M 12 M 24 M 36 M 48 M 60M Clinic visit X X X X X X X Mammogram X X X Blood X X X DXA X

33 Cumulative incidence (%) IBIS-II Breast Cancer Incidence All breast cancer: HR=0.47 ( ), P< % 2.8% Number at risk Follow-up time [years] Placebo Anastrozole Placebo Anastrozole Cuzick et al Lancet 2014

34 Conclusions 5 years of tamoxifen produces a very long term 30% reduction of breast cancer Aromatase inhibitors are more effective (>50% reduction) and less toxic ( no endometrial cancer or thromboembolic complications), but only suitable for postmenopausal women Further work needed to explore new preventive treatments for premenopausal women and oestrogen receptor negative disease