HORMONAL TREATMENT

FOR POSTMENOPOUSAL

BREAST CANCER

1

Annual Hazard of Recurrence Peaks at 2 Years Regardless of Baseline Prognostic Factors

0

5

10

15

20

25

0.5 1.5 2.5 3.5 4.5 5.5 6.5 7.5 8.5 9.5 10.5

Ha

zard

of

recu

rren

ce b

y ye

arl

y in

terv

al

Time (years)

Total population

Node 0

Node (+4)

Postmenopausal

Premenopausal

ER+

ER-

Tumour size <1 cm

Tumour size >3 cm

Ref :Saphner T et al. J Clin Oncol. 1996; 14: 2738–2746

Intrinsic subtype of breast cancer (St Gallen 2013) which is also recommended by ESMO Clinical Practice Guidelines for making the prognosis and treatment decision

Ref :Senkus E et al. Annals of Oncology .2013:1-17

Systemic Treatment Recommendation in Early Breast Cancer

Ref :Senkus E et al. Annals of Oncology .2013:1-17

Endocrine Therapy for postmenopausal patients

• Aromatase inhibitors (AIs) and Tamoxifen are the valid options.

•AIs effectively prolong Disease-Free Survival and may be given as upfront, or switching after 2-3 years of Tamoxifen or extended adjuvant (after 5 years of Tamoxifen)

•There is no benefit of using AIs for more than 5 years

•The use of Tamoxifen is associated with increased risk of thromboemboliccomplications and endometrial hyperplasia/cancer

• Patients on AIs should be advised to assure adequate calcium + vitamin D3 supply and assess bone mineral density periodically

Ref :Senkus E et al. Annals of Oncology. 2013:1-17

First-generation Second-generation Third-generation

aminoglutethimi

de

Fadrozole

Formestane

Anastrozole

Letrozole

Exemestane

3. Aromatase Inhibitor

For Postmenopausal BC ER/PR +

Sites of peripheral aromatisation

Breast

tumour Muscle

Fat Liver

The peripheral aromatase system is the main source of circulating oestrogenic

steroids in

post-menopausal women.

Aromatase Inhibitor inhibit the production oestrogen in

peripheral tissue

Aromatase inhibition within the breast

tumour cell

ANDROGENS OESTROGENS

P-450 Aromatase

+ NADPH-cytochrome P-450 reductase

(Testosterone,

androstenedione,

16-OH-testosterone)

(Oestradiol, oestrone)

Aromatase Inhibitors

tumour

growth

ARIMIDEX® (anastrozole) : Long term efficacy and tolerability

Ref : Cuzick J et al. Lancet Oncol. 2010; 11:1135-1141

9366 postmenopausal women with localised

invasive breast cancer

Surgery radiotherapy chemotherapy

Randomisation 1:1:1 for 5 years

Anastrozole

n=3125

Tamoxifen

n=3116Combination

n=3125

Regular follow-up

Primary trial endpoints:

• Disease-free survival

• Safety / tolerability

Secondary trial endpoints:

• Incidence of contralateral breast cancer

• Time to distant recurrence

• Overall survival

• Time to breast cancer death

ATAC Trial Design

ATAC Trialists' Group. Lancet Oncol. 2008; 9: 45-53

Discontinued

After 10 years of follow-up...

Time to Recurrence in hormone receptor-positive patients

010

20

30

0 1 2 3 4 5 6 7 8 9 10

Pati

en

ts (

%)

Follow-up time (years)

2618

2598

2541

2516

2452

2398

2362

2304

2279

2195

2163

2086

2028

1934

1896

1796

1728

1650

1542

1453

At risk:

A

T

800

753

Tamoxifen (T)

Anastrozole (A)

12.5%

9.8%

19.7%

24.0%

Absolute

difference

2.7%

Absolute

difference

4.3%

Ref :Cuzick J et al. Lancet Oncol. 2010; 11:1135-1141

ARIMIDEX® reduces the risk of recurrence by 21% (HR=0,79. 95%CI=0,70- 0,89;p=0,0002)

Contralateral Breast Cancer (CLBC)

Reference :Cuzick J et al. Lancet Oncol. 2010; 11:1135-1141

ARIMIDEX® significantly reduces the risk of contralateral breast cancer by 38%compared to tamoxifen in HR+ve patients (HR=0,62 (0.45-0.85), p=0,003)

Cuzick J et al. Lancet Oncol. 2010; 11:1135-1141

ATAC 10 years tolerability profile

ARIMIDEX® is NOT the same with other AIs

ARIMIDEX® vs other AIs

Ref :

1.Buzdar A. et al. Cancer 2002:95:2006-2016

2. MIMS Indonesia January 2015

ARIMIDEX® Letrozole Exemestane

Drug classification1 Non steroid Non streoid Steroid

Indicated as upfrontadjuvant therapy in breast cancer with HR +ve2

Yes Yes No

Time to achieve steady-state in plasma1

7 days 60 days 7 days

Androgenic properties1 No No Yes

Lipid profiles1 No change Increased total cholesterol, LDL and apoB

Decreased total cholesterol, HDL, apoA1 and TGA

Ref :The ATAC Trialists Group. Lancet 2005;365:60-62

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Ref: Coates et al. J Clin Oncol. 2007:25 : 486-492

Letrozole is associated with higher

cardiac events and

hypercholesterolemia than

tamoxifen

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SUMMARY

Breast cancer recurrence peaks at the first two years of adjuvant treatment regardless of tumor size and nodal involvement

ARIMIDEX® as upfront adjuvant therapy is significantly more superior than tamoxifen in reducing all kind of recurrences

ARIMIDEX® is proven to have a better tolerability profile than tamoxifen during treatment period. After treatment completion, ARIMIDEX® show no permanent effect on fracture rates

ARIMIDEX® is a non steroid aromatase inhibitor which has shown no significant impact on patients lipid profile compared to other AIs.

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