辉瑞乳腺癌内分泌治疗
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1.Jordan VC 1999 Melville, NY. PRR, Inc 2.Lancet.1983 Feb 5;1(8319):257-61. 3.JNCI 1996:88;1543-9 4.JNCI, Vol. 93, No. 6, 456-462, 2001 5.JNCI 1996:88;1529-42 6.Lancet. 1998,vol 351,(9114):1451-1467
SIR G. T. BEATSON
Hierarchy of evidence on ovarian ablation for breast cancer Continued maintenance of the review
2000+ Continued maintenance of the review 2000 Next cycle of review by Early Breast Cancer Trialists' Collaborative Group 1998 Review published as Cochrane review 1996 Second full review published in Lancet 1992 First full review is published 1990 Partial review is published 1983 Early Breast Cancer Trialists' Collaborative Group is formed 1948 First randomised trial begins 1900+ Case series and non-randomised studies are published 1896 Beatson publishes first case report 1889 Schinzinger suggests possible use
Fisherian theory
肿瘤细胞扩散无固定模式 ，区域淋巴结对播散无屏障作用，反映肿瘤生物学行为 血行播散与淋巴转移无相关性，局部复发为血行播散的局部表现，是预后决定因素 不同局部治疗方式对生存率无影响，NSABP B-04 三期临床试验肯定保乳手术疗效： NSABP B-06 (Bernard Fisher), Milan Cancer Institute (Umberto Veronesi)
Sir George Thomas Beatson, He took his degree from Clare College, Cambridge, in 1869, studied medicine at Edinburgh University. He was later examiner in surgery at Edinburgh; Consulting Surgeon to Glasgow Infirmary and Chairman of the Scottish Branch of the Royal Red Cross Society end the St. Andrew's Ambulance Association. He died at Glasgow in 1933
中国, 上海
日本, 大阪
日本, Yamagata
美国, 洛杉矶: 韩国人
0
20
40
60
80
100
世界女性乳腺癌发病率, 1988-1992
Cancer Incidence in Five Continents, Vol. VII,1988-1992
肿瘤的内在特性
乳癌内分泌治疗的挑战
Breast cancer ---heterogeneous disease, ER+ /- tumors Predict risk---difficult "one size fits all" ? Endocrine therapy may be the best or only systemic treatment Optimal endocrine therapy: Based on varied response to endocrine therapy. individuation?
意大利, 帕尔马
丹麦
瑞典
美国, 洛杉矶: 菲律宾人
英国, 英格兰和威尔士
美国, 洛杉矶: 日本人
德国, 东部洲
新加坡: 中国人
美国, 洛杉矶: 中国人
香港
台湾
ຫໍສະໝຸດ Baidu
90.7
79.3
77.2
77.1
76.8
73.6
73.3
72.9
69.3
68.8
63
48.2
39.5
36.8
34
26.8
26.5
24.3
22.7
21.4
美国,SEER: 白人
美国,SEER: 黑人
新西兰: 非毛利人
新西兰: 毛利人
加拿大
Cancer Registry Annual Report Republic of China, 1993-1998
每100,000 人口发病
乳腺癌发病的最关键因素 —雌激素作用
综合治疗（立体治疗）
SERMs
1967年 Jensen发现 ER---hormonal responsive marker Tamoxifen Golden standard
Tamoxifen evidence (adjuvant)
In 1986, as monotherapy for early breast cancer in node-positive, postmenopausal women.1 NATO (The Nolvadex Adjuvant Trial Organisation 1983)2 evaluate the effectiveness in early breast cancer. The Stockholm trial (1996)3 The Scottish trialists group(2001)4 NSABP B-14 trial (1996)5 EBCTCG (1998)6
Endocrine pathways and the breast
卵巢切除
George Beatson, was the first to publish a case report. He postulated an association between the hormonal action of the ovaries and the proliferation of breast cells and tested this in June 1895. A 33 year old woman had noticed a small lump on her left breast when breast feeding her first child. This lump got larger after the birth of her second baby and she went to the Glasgow Royal Infirmary. A 12 cm tumour was removed but the cancer was already far advanced. She was referred to the Glasgow Cancer Hospital, and Beatson removed both her ovaries. The woman survived for nearly four years before dying of recurrent disease. He reported the case to the Edinburgh Medico-Chirurgical Society and published details in the Lancet in July 1896. 这是乳腺癌作为全身性疾病治疗的开始
外科治疗 放疗 化疗 内分泌治疗 分子靶向治疗
对乳腺癌认识的演变
Hippocrates和Galen的black bile学说
12世紀，William of Salicet(1210-1277) ，那些發瘋的黑色膽汁是包含於乳房內的血管。當時使用caustics(浸蝕劑)，使乳房腐爛 Andeas Versalius(1514-1564) 《人體構造》，以外科切除術來治療乳癌 1757年Le Dran，乳癌加腋下淋巴結腫大，其預後較差，建立起乳癌是一個局部疾病的觀念 有描述記載的乳房腫瘤切除是拿坡崙外科醫師Larrey为D`Ablay夫人所作的手術。她描寫〝外科醫師使用刀子從我的胸骨上把乳房刮起來〞，前後只花20分鐘，Larrey醫師臉色蒼白，但被血液噴的全臉都是血，醫師的表情悲傷、害怕、恐懼到似乎要死去一樣。
Systemic disease onset
Breast Conserving treatment
Umberto Veronesi , M. D.
Bernard Fisher, M.D.
Spectrum theory
1980年 Samuel Hellman（芝加哥大學）提出， spectrum意思：部份乳癌，雖然沒有局部淋巴結轉移，但確有遠處轉移，相反，有一些病灶已經很大，但卻沒有淋巴結或遠處轉移，大部份乳癌是屬於中間型 這個觀念是對淋巴結、淋巴管道、淋巴循環系統的解剖學、生理學、生物學行為以及分子生物學的瞭解所引發出來的新觀念
古代手術代表著痛苦、殘害
Halstedian theory
G.Morgagni 病理解剖學，Rudolf Virchow 細胞病理學 1846年William Morton乙醚全身麻醉示範成功 1867年J.Lister消毒滅菌概念的確立 Halsted 发表，The results of operations for the cure of cancer of the breast performed at Johns Hopkins hospital from June 1889 to January 1894 〝the efficiency of an operation is measured truer in terms of local recurrence than ultimate cure〞。 當時局部再發率: 60-82% 肿瘤扩散有一定规律，由区域淋巴结到全身
Halsted’s radical mastectomy 19th~20th(50yrs)
William Stewart Halsted born Sept. 23, 1852, New York, N.Y., U.S. died Sept. 7, 1922, Baltimore, Md. American pioneer of scientific surgery who established at Johns Hopkins University, Baltimore
SIR G. T. BEATSON
Hierarchy of evidence on ovarian ablation for breast cancer Continued maintenance of the review
2000+ Continued maintenance of the review 2000 Next cycle of review by Early Breast Cancer Trialists' Collaborative Group 1998 Review published as Cochrane review 1996 Second full review published in Lancet 1992 First full review is published 1990 Partial review is published 1983 Early Breast Cancer Trialists' Collaborative Group is formed 1948 First randomised trial begins 1900+ Case series and non-randomised studies are published 1896 Beatson publishes first case report 1889 Schinzinger suggests possible use
Fisherian theory
肿瘤细胞扩散无固定模式 ，区域淋巴结对播散无屏障作用，反映肿瘤生物学行为 血行播散与淋巴转移无相关性，局部复发为血行播散的局部表现，是预后决定因素 不同局部治疗方式对生存率无影响，NSABP B-04 三期临床试验肯定保乳手术疗效： NSABP B-06 (Bernard Fisher), Milan Cancer Institute (Umberto Veronesi)
Sir George Thomas Beatson, He took his degree from Clare College, Cambridge, in 1869, studied medicine at Edinburgh University. He was later examiner in surgery at Edinburgh; Consulting Surgeon to Glasgow Infirmary and Chairman of the Scottish Branch of the Royal Red Cross Society end the St. Andrew's Ambulance Association. He died at Glasgow in 1933
中国, 上海
日本, 大阪
日本, Yamagata
美国, 洛杉矶: 韩国人
0
20
40
60
80
100
世界女性乳腺癌发病率, 1988-1992
Cancer Incidence in Five Continents, Vol. VII,1988-1992
肿瘤的内在特性
乳癌内分泌治疗的挑战
Breast cancer ---heterogeneous disease, ER+ /- tumors Predict risk---difficult "one size fits all" ? Endocrine therapy may be the best or only systemic treatment Optimal endocrine therapy: Based on varied response to endocrine therapy. individuation?
意大利, 帕尔马
丹麦
瑞典
美国, 洛杉矶: 菲律宾人
英国, 英格兰和威尔士
美国, 洛杉矶: 日本人
德国, 东部洲
新加坡: 中国人
美国, 洛杉矶: 中国人
香港
台湾
ຫໍສະໝຸດ Baidu
90.7
79.3
77.2
77.1
76.8
73.6
73.3
72.9
69.3
68.8
63
48.2
39.5
36.8
34
26.8
26.5
24.3
22.7
21.4
美国,SEER: 白人
美国,SEER: 黑人
新西兰: 非毛利人
新西兰: 毛利人
加拿大
Cancer Registry Annual Report Republic of China, 1993-1998
每100,000 人口发病
乳腺癌发病的最关键因素 —雌激素作用
综合治疗（立体治疗）
SERMs
1967年 Jensen发现 ER---hormonal responsive marker Tamoxifen Golden standard
Tamoxifen evidence (adjuvant)
In 1986, as monotherapy for early breast cancer in node-positive, postmenopausal women.1 NATO (The Nolvadex Adjuvant Trial Organisation 1983)2 evaluate the effectiveness in early breast cancer. The Stockholm trial (1996)3 The Scottish trialists group(2001)4 NSABP B-14 trial (1996)5 EBCTCG (1998)6
Endocrine pathways and the breast
卵巢切除
George Beatson, was the first to publish a case report. He postulated an association between the hormonal action of the ovaries and the proliferation of breast cells and tested this in June 1895. A 33 year old woman had noticed a small lump on her left breast when breast feeding her first child. This lump got larger after the birth of her second baby and she went to the Glasgow Royal Infirmary. A 12 cm tumour was removed but the cancer was already far advanced. She was referred to the Glasgow Cancer Hospital, and Beatson removed both her ovaries. The woman survived for nearly four years before dying of recurrent disease. He reported the case to the Edinburgh Medico-Chirurgical Society and published details in the Lancet in July 1896. 这是乳腺癌作为全身性疾病治疗的开始
外科治疗 放疗 化疗 内分泌治疗 分子靶向治疗
对乳腺癌认识的演变
Hippocrates和Galen的black bile学说
12世紀，William of Salicet(1210-1277) ，那些發瘋的黑色膽汁是包含於乳房內的血管。當時使用caustics(浸蝕劑)，使乳房腐爛 Andeas Versalius(1514-1564) 《人體構造》，以外科切除術來治療乳癌 1757年Le Dran，乳癌加腋下淋巴結腫大，其預後較差，建立起乳癌是一個局部疾病的觀念 有描述記載的乳房腫瘤切除是拿坡崙外科醫師Larrey为D`Ablay夫人所作的手術。她描寫〝外科醫師使用刀子從我的胸骨上把乳房刮起來〞，前後只花20分鐘，Larrey醫師臉色蒼白，但被血液噴的全臉都是血，醫師的表情悲傷、害怕、恐懼到似乎要死去一樣。
Systemic disease onset
Breast Conserving treatment
Umberto Veronesi , M. D.
Bernard Fisher, M.D.
Spectrum theory
1980年 Samuel Hellman（芝加哥大學）提出， spectrum意思：部份乳癌，雖然沒有局部淋巴結轉移，但確有遠處轉移，相反，有一些病灶已經很大，但卻沒有淋巴結或遠處轉移，大部份乳癌是屬於中間型 這個觀念是對淋巴結、淋巴管道、淋巴循環系統的解剖學、生理學、生物學行為以及分子生物學的瞭解所引發出來的新觀念
古代手術代表著痛苦、殘害
Halstedian theory
G.Morgagni 病理解剖學，Rudolf Virchow 細胞病理學 1846年William Morton乙醚全身麻醉示範成功 1867年J.Lister消毒滅菌概念的確立 Halsted 发表，The results of operations for the cure of cancer of the breast performed at Johns Hopkins hospital from June 1889 to January 1894 〝the efficiency of an operation is measured truer in terms of local recurrence than ultimate cure〞。 當時局部再發率: 60-82% 肿瘤扩散有一定规律，由区域淋巴结到全身
Halsted’s radical mastectomy 19th~20th(50yrs)
William Stewart Halsted born Sept. 23, 1852, New York, N.Y., U.S. died Sept. 7, 1922, Baltimore, Md. American pioneer of scientific surgery who established at Johns Hopkins University, Baltimore