HORMONAL TREATMENT IN BREAST

CANCER PRE AND POST MENOPAUSAL

Djoko H. Hermanto
Hematology-Medical Oncology Division, Department of Internal Medicine
Faculty of Medicine, Brawijaya University - Dr. Saiful Anwar General Hospital Malang
INDONESIA
Globocan 2012
 Annual Hazard of Recurrence Peaks at 2 Years Regardless of Baseline
Prognostic Factors

Total population
Node 0
Node (+4)
25
Tumour size >3 cm
Tumour size <1 cm
Hazard of recurrence by yearly

ER-
20 ER+
Premenopausal
15 Postmenopausal
interval

10

0
0.5 1.5 2.5 3.5 4.5 5.5 6.5 7.5 8.5 9.5 10.5

Time (years)
Ref :
Saphner T et al. J Clin Oncol. 1996; 14: 2738–2746
 Medical management of BC

1. Systemic chemotherapy: Non-Trastuzumab and

Trastuzumab containing regimens.
2. Endocrine (hormone) therapy :
 Anti estrogens: tamoxifen, toremifene and raloxifene
 Aromatase inhibitors (AIs): anastrozole, letrozole,
and exemestane
 Progestin, androgens hormone, LHRH agonist
3. Targeted therapy: trastuzumab, lapatinib,
bevacizumab, pertuzumab.
 Antagonizing Estrogen Dependent
Growth in Breast Cancer

Premenopausal Pre- and Postmenopausal

Extragonadal
Ovaries Peripheral fat, skin, muscle, bone, CNS, breast and
peritumoral fibroblast, metastases
OFS
GnRH inhibitors AIs
or OVX Estrogen
ER
ER

Tamoxifen

AI, aromatase inhibitor X

ER, estrogen receptor
GnRH, gonadotropin-releasing hormone Cancer cell
OFS, ovarian function suppression
OVX, ovariectomy
 Rationale for Endocrine Therapy
• Nearly one third of women are diagnosed with
invasive breast cancer before 50 years of age

• The majority of these cancers will be hormone

receptor positive (Luminal A and Luminal B)
 Systemic Treatment Recommendation for 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)
• The use of Tamoxifen is associated with increased risk of
thromboembolic complications 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
 AROMATASE INHIBITORS PROFILE
ANASTROZOLE LETROZOLE EXEMESTANE

Drug classification1 Non steroid Non streoid Steroid

Indicated as upfront Yes Yes No

adjuvant therapy in
breast cancer with HR
+ve2
Time to achieve steady- 7 days 60 days 7 days
state in plasma1

Androgenic properties1 No No Yes

Lipid profiles1 No change Increased total Decreased total

cholesterol, LDL and cholesterol, HDL,
apo B apo A1 and TGA
Ref :
1.Buzdar A. et al. Cancer 2002:95:2006-2016
2. MIMS Indonesia January 2015
 ATAC Trial Design
9366 postmenopausal women with localised
invasive breast cancer

Surgery  radiotherapy  chemotherapy

Randomisation 1:1:1 for 5 years

  
Anastrozole Tamoxifen Combination
n=3125 n=3116 n=3125
Discontinued

Regular follow-up

Primary trial endpoints: Secondary trial endpoints:
• Disease-free survival • Incidence of contralateral breast cancer
• Safety / tolerability • Time to distant recurrence
• Overall survival
• Time to breast cancer death

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

After 10 years of follow-up...
 Time to Recurrence in hormone receptor-positive patients
ANASTROZOLE reduces the risk of recurrence by 21%
(HR=0,79. 95%CI=0,70- 0,89;p=0,0002)

Tamoxifen (T) Absolute

30

Anastrozole (A) difference

4.3%
24.0%
20

Absolute
Patients (%)

difference
2.7% 19.7%
12.5%
10

9.8%
0

0 1 2 3 4 5 6 7 8 9 10
Follow-up time (years)
At risk:
A 2618 2541 2452 2362 2279 2163 2028 1896 1728 1542 800
T 2598 2516 2398 2304 2195 2086 1934 1796 1650 1453 753
Ref :
Cuzick J et al. Lancet Oncol. 2010; 11:1135-1141
 ATAC 10 years tolerability profile

ON TREATMENT OFF TREATMENT

OR OR
ANASTRO- TAMOXIFEN (95% CI) ANASTRO- TAMOXIFEN (95% CI)
ZOLE ZOLE

Treatment- 0,57 0,84

related 223 369 (0,48 - 0,69); 66 78 (0,60 - 1,19);
serious P<0,0001 p = 0,3
adverse event
1,33 0,98
Fracture rates 451 351 (1,15 - 1,55) 110 112 (0,74 - 1,30);
P<0,0001 p = 0,9

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

Ref :
The ATAC Trialists Group. Lancet 2005;365:60-62
 SUMMARY
 Breast cancer recurrence peaks at the first two years of adjuvant
treatment regardless of tumor size and nodal involvement

Endocrine therapy is preferable to chemo in 1st line for ER(+) ABC

(unless life-threatening disease)

Anastrozole as upfront adjuvant therapy is significantly more

superior than tamoxifen in reducing all kind of recurrences

Anastrozole is a non steroid aromatase inhibitor which has shown no

significant impact on patients lipid profile compared to other AIs.