Dubai meet 2015

1. HORMONAL THERAPY FOR
BREAST CANCER

2.  Breast cancer is the 2nd most common malignancy diagnosed throughout the
world and is the 5th most common cause of cancer related death
 In women throughout the world, it is the most common malignancy diagnosed
and is the most common cause of death
 Around 60-70% patients diagnosed to have breast cancer are Estrogen receptor-
positive (65% of these are also positive for Progesterone receptors)
INTRODUCTION

3.  Patients with Estrogen receptor-Positive (ER+) tumors have a better survival than
tumors with no Estrogen receptors (ER-)
 Five-year survival is about 10 % better for women with ER+ breast cancer than for
those with ER- tumors
 Patients with ER + tumors are candidates for hormonal therapy
INTRODUCTION

4. Study Study
Population
Characteristics
of patients
Follow up
(Years)
ER + ER -
SEER 111,993 Stage I, II or III 8 Women
younger than
40:
90%*Sig
Women 40-49:
94%*Sig
Women 50-59:
95%*Sig
Women 60-69:
95%*Sig
Women 70-74:
94%*Sig
Women
younger than
40:
78%*Sig
Women 40-49:
81%*Sig
Women 50-59:
81%*Sig
Women 60-79:
81%*Sig
Women 70-74:
80%*Sig
5 YEAR OVERALL SURVIVAL

5. Study Study
Population
Characteristics
of patients
Follow up
(Years)
ER + ER -
Danish Breast
Cancer
Cooperative
Group
26,944 Grade I, II or III 5 85% 69%
Truong et al. 8,038 T1-2, M0
Grade I, II, or III
4-6 Higher
survival
Sig
Lower
survival
Sig
San Antonio
Data Base
3,452 Stage I, II or III 3 84% 75%Sig
Crowe et al. 1,392 Stage I or II 10 82% 70%Sig
NSABP B-06 1,157 Node-negative
Tumor smaller than
4 cm
5 92% 82%Sig
Winstanley et al. 767 Stage I or II 11 69% 62%NS
Crowe et al. 501 Stage I
Node-negative
7 94% 80%Sig

6.  1971 – Christie Hospital, Manchester
 1st Clinical study of Tamoxifen in Advanced Breast Cancer
HISTORY AND EVOLUTION

7.  1973 – 1st work done on Aromatase Inhibitors in treatment of Breast cancer
HISTORY AND EVOLUTION

8. TIMELINE OF DEVELOPMENT OF AGENTS IN
BREAST CANCER

9. MOLECULAR BASIS
 Overexpression of Estrogen receptors is seen in a large number of breast cancer
patients (~70%)
 Estrogen :
 Steroid hormone
 Profound proliferative effect on normal human mammary epithelium through its
activation of ER-alpha, a classic nuclear hormone receptor
 Exerts its actions through both genomical and nongenomical mechanisms

10.  Genomic Mechanism :
 Involves binding of hormones to their respective receptors, transcription of the specific
genes, and protein synthesis
 Sequence of events often takes hours to days
 Non Genomic Mechanism :
 Involves the modulation of neurotransmission unrelated to the transcription of genes
 May occur within seconds to minutes
MOLECULAR BASIS

13. AGENTS USED IN HORMONAL THERAPY
 Selective Estrogen Receptor Modulators (SERM)
 Tamoxifen
 Raloxifen
 Torimefene
 Anti Estrogens
 Fulvestrant
 Aromatase Inhibitors
 Letrozole
 Anastrazole
 Exemestane
 LHRH Agonists
 Leuprolide
 Goserlin
 Progestins
 Megestrol acetate
 Medroxyprogesterone acetate

14. SERD vs SERM

15. CONCLUSIONS
 Endocrine therapy is a safe and well tolerated targeted treatment modality in
majority of patients with breast cancer
 In the adjuvant setting primary treatment with Tamoxifen should be considered in
all receptor positive pre menopausal females
 Ovarian ablation may have additive benefits with Tamoxifen in premenopausal
females
 Aromatase Inhibitors have a major role to play in hormone positive post
menopausal females