Medicines and Breast Cancer: From population to patient

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1 RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Medicines and Breast Cancer: From population to patient Kathleen Bennett, Associate Professor and HRB Research Leader

2 Aspirin and cancer Derived from the bark of the willow tree; is an irreversible inhibitor of cyclo-oxygenase Marketed in 1899 by Bayer as an analgesic now one of the most prescribed drugs in the world. WHO list of essential medicines. Evidence emerging that links aspirin to reduced cancer risk, metastatic disease and death. Laboratory evidence suggests aspirin might reduce risk and the spread of cancer via various mechanisms. 2

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5 Overall HR 0.82 After 5 yrs HR 0.66, p=0.003 Individual patient data 7 Randomised Trials 75mg Aspirin Daily Patients

% R i s k Lancet PMID: 22440947 spirin Risk of 3.0 Distant Metastasis (All Sites) 2.5 Meta-Analysis 2.

6 % R i s k Lancet PMID: spirin Risk of 3.0 Distant Metastasis (All Sites) 2.5 Meta-Analysis 2.0 c o n t r o l 5 Randomised Trials 75mg Aspirin Daily 17,285 Patients HR 0.64, P= a s p i r i n Y e a r s 12

7 Lancet PMID: spirin Risk of Distant Metastasis OR 95% CI Colorectal Meta-Analysis 5 Randomised Trials 75mg Aspirin Daily Other GI ,285 Patients Breast Prostate

8 Breast Cancer the facts In Ireland.. Worldwide..

9 Published Aug 2014 Irish times 9

10 Pre-diagnostic aspirin and lymph node status RR l y m p h n o d e m e t a s t a s i s Aspirin Use Infrequent Use Frequent Use spirin

11 B r e a s t c a n c e r s p e c i f i C M o r t a l i t y P r o b a b i l i t y Pre-diagnostic aspirin and lymph node status 0.25 Full Cohort HR 0.80, 95%CI Node Positive HR 0.91, 95%CI Node Negative HR 0.55, 95%CI C o n t r o l C o n t r o l C o n t r o l P r e - d i a g n o s i s A s p i r i n 0.10 P r e - d i a g n o s i s A s p i r i n P r e - d i a g n o s i s A s p i r i n Y e a r s Y e a r s Y e a r s

12 Aspirin and Breast cancer Population to patient Better understanding of the mechanisms required To identify women most likely to benefit from taking aspirin On-going research Will help to identify biomarkers in personalising medicine for women with breast cancer Collaboration with diverse disciplines with a common goal

13 Hormonal therapy for breast cancer; barriers and enablers to medication taking behaviour (MTB) 5 to 10 years of adjuvant hormonal treatment reduces recurrence (50%) and mortality in estrogen receptor positive cases. Rates of non-persistence range 31-73% in routine clinical settings at 5 years Our own HRB research found 22% non-persistence at 1 year and 35% at 3.5 years in an Irish Breast Cancer cohort Barron TI, et al. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer

14 Women who were non-persistent ( 180 days without hormonal therapy) compared to persistent to therapy had almost three-fold increased risk of recurrence (OR 2.88; 95%CI 1.11, 7.46)

15 HRB funded research helped to identify modifiable influences using qualitative methods guided by theoretical domains framework Persistent, non-persistent or non-adherent (n=31 women) 3 key domains identified both barriers and enablers to hormonal therapy MTB across the strata; beliefs about consequences, intentions and goals and behaviour regulation 15

16 Selected quotes from patients Beliefs about Consequences I wasn t prepared to feel the way I felt, I felt so horrible...i think I'd rather take the risk with cancer than feel miserable, unhappy, fat (NP) Intentions and goals I don t think I want this I wanted to be finished with the treatment, I d had the operation, I d had the chemo, I had the radiotherapy (NP) Behaviour regulation I might as well be dead I thought as feeling like this. Physically, mentally, just totally. I can't see the point in prolonging life if you're miserable and you have no quality of life, and that s how I felt on the tablets (NP) 16

17 Summary The behavioural analysis helps identify what needs to change to improve hormonal therapy MTB Identifying and targeting these modifiable influences in clinical practice will help improve hormonal therapy MTB and survival in this population This research is informing the development and evaluation of theory based behavioural interventions to improve hormonal therapy MTB 17

Cathy Kelly (Mater) PhD/postdoctoral researchers E Flahavan, A Smith, Dr C Cahir, Dr L Murphy, Dr I Barron.

18 Acknowledgements HRB, Irish Cancer Society funding NCRI, HSE-PCRS, HSE Collaborators RCSI, TCD, UCD, Cancer trials Ireland (formerly ICORG), Newcastle, Stirling Universities UK, John Hopkins USA, Prof M John Kennedy (SJH), Dr Cathy Kelly (Mater) PhD/postdoctoral researchers E Flahavan, A Smith, Dr C Cahir, Dr L Murphy, Dr I Barron. We wish to thank all of the women at the two cancer centres who kindly gave their time to participate in the qualitative study.

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20 Randomised trials ADD ASPIRIN Evidence that aspirin may be effective against cancers with the genetic mutation PIK3CA, but more robust studies are necessary.

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