乳腺癌辅助内分泌治疗相关试验
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乳腺癌的内分泌治疗
2020/11/4
1
乳癌内分泌治疗历史
1896年 卵巢切除术治疗复发转移乳癌
1922年 放疗卵巢去势
1939年 雄性激素
1944年 人工合成雌激素
1951年 孕激素
1953年 肾上腺切除和下丘脑切除
1973年 三苯氧胺
1981年 芳香化酶抑制剂
1990‘s 新一代的芳香化酶抑制剂
Risk reduction by age, (ER+)
54
45
37
32
34
Recurrence Mortality 11
<50
50-59
>60
patient age (years)
8
Tamoxifen Adjuvant Therapy for Breast Cancer (IV)
no. of cases
2020/11/4
17
Survival Data Anastrozole / MA
60 50 40 30 20 10
0
2020/11/4 Median time to death(months)
P < 0.05
2 year survival rate (%)
Arimidex MA
18
Femara® ( letrozole ) vs
10
34 17
28
Recurrence
Mortality
0 2020/11/4 1 year
2 yrs
5 yrs of therapy
6
Tamoxifen Adjuvant Therapy for Breast Cancer (II)
Risk reduction by ER status (5yrs therapy)
25
21个月
P=0.03
20 14个月
15
10
5
0
2020/11/4 Femara 0.5mg Femara 2.5mg
AG 500mg
16
Anastrozole (Arimdex) vs
Megestrol Acetate in Advanced Breast Cancer
Phase III Trials
Adrenal gland
Peripheral tissues
Aromatase
Aromatase
= Estrogen =20A20/n11d/4rostenedione
Receptor
Tumor
Postmenopausal wo10men
Anti-Aromatase Agents: Mechanism of Action
2020/11/4
14
Femara > AG
Clinical Benefit (CR+PR+SD>=6 个月) %
40%
P=0.03
30%
20%
10%
0% Femara 0.5mg
2020/11/4
Femara 2.5mg
AG 500mg
15
Femara > AG
Median Duration of Clinical Benefit (months)
women.
Lancet 1998; 351: 1451
2020/11/4
5
Tamoxifen Adjuvant Therapy for Breast Cancer (I)
Reductions in risk in ER+ patients
60 51
50
% reduction
40
30 22
20 11
11
Anti-Aromatase Agents by Generation
Generation
Nonsteroidal Inhibitors
Steroidal Inactivators
First
Aminoglutethimide Testolactone
Second
Fadrozole
Formestane
Incidence in >20,000 patient follow-up years
160 140 120 100 80 60 40 20
0
2020/11/4
157 91
contralat. b.c.
42 9
Endometrial cancer
Placebo Tamoxifen
9
The Role of Aromatase in Estrogen Biosynthesis and Tumor Growth
Tamoxifen
as First0-Li2ne5Therapy
2020/11/4
50 50
40
37
30
20
10
6
28
21 Recurrence Mortality
% reduction
0
-3
-10
2020/11/4 ER poor
ER unknown
ER +ve
7
% reduction
60 50 40 30 20 10
0
2020/11/4
Tamoxifen Adjuvant Therapy for Breast Cancer (III)
Cholesterol
Pregnenolone
Cortisol
Progesterone Aldosterone
2020/11/4
Androstenedione
Testosterone
Aromatase Inactivators
and
Aromatase Inhibitors
Estrone
Estradiol
Third
2020/11/4
Anastrozole Letrozole
Exemestane
12
高选择性芳香化酶抑制剂
选择性抑制芳香化酶
作用强度更强
不良反应更轻
2020/11/4
13
Femara (Letrozole) vs
Aminoglutethimide (AG)
Phase III Trial
2020/11/4
2
乳癌内分泌治疗药物
乙来自百度文库雌酚 雌激素
MPA MA 孕激素
TAM 抗雌激素
Droloxifene Toremifene
AG
Zoladex
芳香化酶抑制 (失活) 剂
兰他隆
Exemestane Arimidex
肾上腺皮质激 素类
Femara (Letrozole)
2020/11/4
3
三苯氧胺 TAM （Tamoxifen,他莫昔芬）
目前最常用的非甾体类抗雌激素药 复发转移乳癌的解救治疗 乳癌术后预防复发转移的辅助治疗 高危健康妇女预防乳癌
2020/11/4
4
Tamoxifen Adjuvant Therapy
Early Breast Cancer Triallists report on 55 trials in 37,000
2020/11/4
1
乳癌内分泌治疗历史
1896年 卵巢切除术治疗复发转移乳癌
1922年 放疗卵巢去势
1939年 雄性激素
1944年 人工合成雌激素
1951年 孕激素
1953年 肾上腺切除和下丘脑切除
1973年 三苯氧胺
1981年 芳香化酶抑制剂
1990‘s 新一代的芳香化酶抑制剂
Risk reduction by age, (ER+)
54
45
37
32
34
Recurrence Mortality 11
<50
50-59
>60
patient age (years)
8
Tamoxifen Adjuvant Therapy for Breast Cancer (IV)
no. of cases
2020/11/4
17
Survival Data Anastrozole / MA
60 50 40 30 20 10
0
2020/11/4 Median time to death(months)
P < 0.05
2 year survival rate (%)
Arimidex MA
18
Femara® ( letrozole ) vs
10
34 17
28
Recurrence
Mortality
0 2020/11/4 1 year
2 yrs
5 yrs of therapy
6
Tamoxifen Adjuvant Therapy for Breast Cancer (II)
Risk reduction by ER status (5yrs therapy)
25
21个月
P=0.03
20 14个月
15
10
5
0
2020/11/4 Femara 0.5mg Femara 2.5mg
AG 500mg
16
Anastrozole (Arimdex) vs
Megestrol Acetate in Advanced Breast Cancer
Phase III Trials
Adrenal gland
Peripheral tissues
Aromatase
Aromatase
= Estrogen =20A20/n11d/4rostenedione
Receptor
Tumor
Postmenopausal wo10men
Anti-Aromatase Agents: Mechanism of Action
2020/11/4
14
Femara > AG
Clinical Benefit (CR+PR+SD>=6 个月) %
40%
P=0.03
30%
20%
10%
0% Femara 0.5mg
2020/11/4
Femara 2.5mg
AG 500mg
15
Femara > AG
Median Duration of Clinical Benefit (months)
women.
Lancet 1998; 351: 1451
2020/11/4
5
Tamoxifen Adjuvant Therapy for Breast Cancer (I)
Reductions in risk in ER+ patients
60 51
50
% reduction
40
30 22
20 11
11
Anti-Aromatase Agents by Generation
Generation
Nonsteroidal Inhibitors
Steroidal Inactivators
First
Aminoglutethimide Testolactone
Second
Fadrozole
Formestane
Incidence in >20,000 patient follow-up years
160 140 120 100 80 60 40 20
0
2020/11/4
157 91
contralat. b.c.
42 9
Endometrial cancer
Placebo Tamoxifen
9
The Role of Aromatase in Estrogen Biosynthesis and Tumor Growth
Tamoxifen
as First0-Li2ne5Therapy
2020/11/4
50 50
40
37
30
20
10
6
28
21 Recurrence Mortality
% reduction
0
-3
-10
2020/11/4 ER poor
ER unknown
ER +ve
7
% reduction
60 50 40 30 20 10
0
2020/11/4
Tamoxifen Adjuvant Therapy for Breast Cancer (III)
Cholesterol
Pregnenolone
Cortisol
Progesterone Aldosterone
2020/11/4
Androstenedione
Testosterone
Aromatase Inactivators
and
Aromatase Inhibitors
Estrone
Estradiol
Third
2020/11/4
Anastrozole Letrozole
Exemestane
12
高选择性芳香化酶抑制剂
选择性抑制芳香化酶
作用强度更强
不良反应更轻
2020/11/4
13
Femara (Letrozole) vs
Aminoglutethimide (AG)
Phase III Trial
2020/11/4
2
乳癌内分泌治疗药物
乙来自百度文库雌酚 雌激素
MPA MA 孕激素
TAM 抗雌激素
Droloxifene Toremifene
AG
Zoladex
芳香化酶抑制 (失活) 剂
兰他隆
Exemestane Arimidex
肾上腺皮质激 素类
Femara (Letrozole)
2020/11/4
3
三苯氧胺 TAM （Tamoxifen,他莫昔芬）
目前最常用的非甾体类抗雌激素药 复发转移乳癌的解救治疗 乳癌术后预防复发转移的辅助治疗 高危健康妇女预防乳癌
2020/11/4
4
Tamoxifen Adjuvant Therapy
Early Breast Cancer Triallists report on 55 trials in 37,000