Internato de Ginecologia Wesley Küster 10º Período.

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Internato de Ginecologia Wesley Küster 10º Período Câncer de Mama Triplo Negativo

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  • Internato de Ginecologia Wesley Kster 10 Perodo
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  • O cncer de mama a neoplasia mais comum entre as mulheres. O Cncer de Mama Triplo Negativo (TNBC) Representa 15% a 20% das neoplasias de mama. Current Concept: Triple-Negative Breast Cancer; Foulkes W, Smith I, Reis J; New England J Medicine. 2010 Nov ; 363:1938-48.
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  • Carcinoma in situ: Ductal Lobular Carcinoma Infiltrante: Ductal Lobular Mucinoso Inflamatrio...
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  • Clula Luminal Clula Mioepitelial Membrana Basal Estroma Intralobular Designer: Wesley Kster Lbulo / Ducto Mamrio
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  • luminal A: expresso de RE, RP e Ki-67 =14%; HER- 2 negativo luminal B: RE e/ou RP positivo (s); Ki-67 > 14%; HER-2 negativo HER-2: RE e/ou RP negativo; HER-2 positivo Basal-smile: RE, RP e HER-2 negativos; EGFR e/ou citoqueratina 5 positivo. Invasive Breast Cancer: Recognition of Molecular Subtypes. Strehl JD, Wachter DL, Fasching PA, et al. Breast Care (Basel). 2011;6(4):258-264.
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  • Ausncia de receptor de estrognio Ausncia de receptor de progesterona Ausncia de receptor de HER-2 ( Receptor semelhante ao fator de crescimento de epidrmico) Current Concept: Triple-Negative Breast Cancer; Foulkes W, Smith I, Reis J; New England J Medicine. 2010 Nov ; 363:1938-48.
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  • Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas; Kreike B, van Kouwenhove M, Horlings H, et al. Breast Cancer Res. 2007;9(5):R65.
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  • BRCA 1 e 2 Supressores Tumorais Codificam protenas envolvidas no reparo de DNA Mutao envolvida no tumores de mama hereditrios (90%) 90% dos pacientes com essa mutao so fenotipicamente triplo-negativo Poly(ADP-ribose) polymerase inhibition: a new direction for BRCA and triple-negative breast cancer? Plummer R. Breast Cancer Res. 2011 Aug 16;13(4):218.
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  • ReceptoresTriplo NegativoBasal SimileBRCA 1 Mutado Estrognio-Geral Geral - Progesterona--Geral HER-2-Geral - EGFRFreqente +Geral + CK5 ou CK17Freqente ++Geral + Ciclina EFreqente +Geral + Current Concept: Triple-Negative Breast Cancer; Foulkes W, Smith I, Reis J; New England J Medicine. 2010 Nov ; 363:1938-48.
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  • Schematic illustration of overlap among triple negative breast cancer (TNBC), basal-like, and BRCA1-related tumors
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  • 15% a 20 % dos tumores de mama Mulheres jovens, habitualmente antes da menopausa. Ascendncia africana Ascendncia hispnica ( EUA) Current Concept: Triple-Negative Breast Cancer; Foulkes W, Smith I, Reis J; New England J Medicine. 2010 Nov ; 363:1938-48.
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  • Fatores de Risco: Menarca precoce Primeira gravidez precoce Aumento da paridade Diminuio do aleitamento materno IMC elevado Baixo nvel socioeconmico Triple-negative breast cancer: adjuvant therapeutic options; Gucalp A, Traina TA; Chemother Res Pract. 2011;2011:696208.
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  • O Cncer de Mama Triplo Negativo (TNBC) tm o pior prognstico. o mais agressivo das neoplasias de mama, observando alta tendncia a disseminao precoce H rompimento da correlao seqencial Tamanho do tumor comprometimento linfonodal metstases sistmicas Platinun-based chemoterapy in triple negative breast cancer; Eckstein N, Haas B; Dtsch Med Wochenschr. 2012 Feb ;137(7):333-6.
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  • Maior recorrncia de recidiva nos trs primeiros anos e morte nos cinco primeiros anos. Recidivas alm dos cinco anos so menos comuns Recidiva a distncia ocorre em 33,9% Triple negative breast cancer: unmet medical needs. Pal SK, Childs BH, Pegram M. Breast Cancer Res Treat. 2011 Feb;125(3):627-36.
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  • Fator TempoTriplo Negativo Outros CAs Mama Mdio at a Morte4,2 anos6 anos Morte relacionado a neoplasia aps o diagnstico 10 anos18 anos Mdio para recidiva a distncia2,6 anos5 anos Mximo para recidiva8 anos17 anos Triple-negative breast cancer: clinical features and patterns of recurrence. Dent R, Trudeau M, Pritchard KI, Hanna WM, et al. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34.
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  • Triple-negative breast cancer: Recurrence and survival. Hudis C A, Gianni L The Oncologist 2011;16:1-11 2011 by AlphaMed Press
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  • Mamografia: Presena de leso em massa, com bordas lisas Geralmente sem presena de calcificaes Geralmente sem presena de margens espiculadas USG: Ausncia de halo ecognico TC: Maior captao de contraste TNBCs so menos provveis de ser detectado por qualquer exame de imagem (36% vs 18,6%) Maior chances de se apresentar entre mamografias regulares Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Yang WT, Dryden M, Broglio K, et al. Breast Cancer Res Treat. 2008 Oct;111(3):405-10.
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  • Define prognstico dos pacientes com TNBCs Pacientes com TNBC geralmente desenvolvem metstases viscerais Sobrevida mdia de 13 meses aps diagnstico metasttico Current Concept: Triple-Negative Breast Cancer; Foulkes W, Smith I, Reis J; New England J Medicine. 2010 Nov ; 363:1938-48
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  • Triple-negative cancer Non-triple-negative cancer Brain 30% Lung 40% Bones 10% Liver 20% 10% 20% 30% 40% Figure 2. Sites of First Distant Recurrence in Cases of Metastatic Triple- Negative Breast Cancer as Compared with NonTriple-Negative Breast Cancer. Current Concept: Triple- Negative Breast Cancer; Foulkes W, Smith I, Reis J; New England J Medicine. 2010 Nov ; 363:1938-48.
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  • Metstases Cerebrais Fatores de Risco: Mulheres Jovens Receptores hormonais negativos Aproximadamente 30% Ocorrncia relativamente precoce Sobrevida mdia aps diagnostico de 3 meses Responsvel por 24% das recidivas Survival among women with triple receptor-negative breast cancer and brain metastases ; Dawood S, Broglio K, Esteva FJ, Ann Oncol. 2009 Apr;20(4):621-7
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  • Cirrgico, Radioterapia e Quimioterapia Base do tratamento a Poliquimioterapia TNBCs apresentam melhor resposta a quimioterapia No responsivo a hormonioterapia ou inibidores da HER-2 (Transtuzumab) Maior taxa de resposta patolgica completa (PCR) neoadjuvante, tendo a PCR valor preditivo Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors; Guarneri V, Broglio K, Kau SW, et al. J Clin Oncol. 2006 Mar 1;24(7):1037-44.
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  • Medicaes usadas habitualmente para tratar o cncer de mama: I. CMF (ciclofosfamida, metotrexato e 5- fluorouracil) II. CAF (ciclofosfamida, adriamicina e 5- fluorouracil) III. CEF (ciclofosfamida, epirrubicina e 5- fluorouracil) Triple-negative breast cancer: role of specific chemotherapy agents. Isakoff SJ. Cancer J. 2010 Jan-Feb;16(1):53-61.
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  • Taxanos Docetaxel e Paclitaxel H aumento da PCR em alguns estudos de at 100% com a adio de taxanos Reduo dos indces de recorrncia Se houver alteraes no BRCA-1, h diminuio da resposta dpos TNBCs aos Taxanos No h alteraes na resposta quando h metastase instalada Triple-negative breast cancer: role of specific chemotherapy agents. Isakoff SJ. Cancer J. 2010 Jan-Feb;16(1):53-61.
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  • Platinas Cisplatina e Carboplatina Estudos demonstram que pode ser usado como agente nico na terapia neoadjuvante (PCR mdio de 30%) Tumores com Mutao no BRCA1 so mais sensveis. (PCR 70% como agente nico neoadjuvante) Ensaios clnicos em pacientes metastticos tem demonstrado superioridade das platinas aos esquemas convencionais. Triple-negative breast cancer: role of specific chemotherapy agents. Isakoff SJ. Cancer J. 2010 Jan-Feb;16(1):53-61. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Byrski T, Huzarski T, Dent R, et al. Breast Cancer Res Treat. 2009 May;115(2):359-63
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  • Agentes antiangiognicos Bevacizumab Portadores de TNBCs possuem maior expresso de VEGF (Fator de crescimento endotelial vascular) Utilizado em associao a quimioterapia neoadjuvante Estudos apontam maior PCR ( em mdia 15% ) quando a utilizao do agente antiangiognico. Triple-negative breast cancer: an update on neoadjuvant clinical trials. Amos KD, Adamo B, Anders CK. Int J Breast Cancer. 2012;2012:385978
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  • Inibidores da PARP (Protena envolvida no reparo do DNA) Inipibaribe Atuante em tumores com mutao do gene BRCA 1 e 2 Impede reparo do DNA mutante Aumento da apoptose Potencializa os efeitos dos quimioterapicos. Aumento da taxa de sobrevida global Iniparib plus chemotherapy in metastatic triple-negative breast cancer ; O'Shaughnessy J, Osborne C, Pippen JE, et al. N Engl J Med. 2011 Jan 20;364(3):205-14.
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  • Inibidores do EGFR (Receptor do fator de crescimento epitelial) Cetuximab Anticorpo Monoclonal Expresso de EGFR esto associados a menor sobrevida 60% dos TNBCs possuem receptor No h ao quando atuando sozinho Gefitinib com carboplatina e docetaxel (Apresentam alta sinergia), com melhora da taxa de resposta. Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Corkery B, Crown J, Clynes M, et al. Ann Oncol. 2009 May;20(5):862-7.
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  • Constitui um importante desafio clnico Falta consenso para tratamento desse subgrupo de tumores A identificao de outros biomarcadores necessrio para prever a resposta aos tratamentos especficos e melhorar ainda mais as estratgias de tratamento, seja atravs de novas opes de quimioterapicos ou no futuro com terapias alvo.
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  • O mdico deve estar atento para a falta de associao entre o tamanho do tumor e positividade do linfonodo sentinela, com a tendncia a desenvolver metstases viscerais, no incio do curso da doena e altas taxas de recorrncia distal.
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  • Current Concept: Triple-Negative Breast Cancer; Foulkes W, Smith I, Reis J; New England J Medicine. 2010 Nov ; 363:1938-48. Invasive Breast Cancer: Recognition of Molecular Subtypes. Strehl JD, Wachter DL, Fasching PA, et al. Breast Care (Basel). 2011;6(4):258-264. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas; Kreike B, van Kouwenhove M, Horlings H, et al. Breast Cancer Res. 2007;9(5):R65. Poly(ADP-ribose) polymerase inhibition: a new direction for BRCA and triple-negative breast cancer? Plummer R. Breast Cancer Res. 2011 Aug 16;13(4):218. Triple-negative breast cancer: adjuvant therapeutic options; Gucalp A, Traina TA; Chemother Res Pract. 2011;2011:696208. Platinun-based chemoterapy in triple negative breast cancer; Eckstein N, Haas B; Dtsch Med Wochenschr. 2012 Feb ;137(7):333-6. Triple negative breast cancer: unmet medical needs. Pal SK, Childs BH, Pegram M. Breast Cancer Res Treat. 2011 Feb;125(3):627-36. Triple-negative breast cancer: clinical features and patterns of recurrence. Dent R, Trudeau M, Pritchard KI, Hanna WM, et al. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34. Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Yang WT, Dryden M, Broglio K, et al. Breast Cancer Res Treat. 2008 Oct;111(3):405-10.
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  • Survival among women with triple receptor-negative breast cancer and brain metastases ; Dawood S, Broglio K, Esteva FJ, Ann Oncol. 2009 Apr;20(4):621-7 Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors;Guarneri V, Broglio K, Kau SW, et al. J Clin Oncol. 2006 Mar 1;24(7):1037-44. Triple-negative breast cancer: role of specific chemotherapy agents. Isakoff SJ. Cancer J. 2010 Jan-Feb;16(1):53-61. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Byrski T, Huzarski T, Dent R, et al. Breast Cancer Res Treat. 2009 May;115(2):359-63 Triple-negative breast cancer: an update on neoadjuvant clinical trials. Amos KD, Adamo B, Anders CK. Int J Breast Cancer. 2012;2012:385978 Iniparib plus chemotherapy in metastatic triple-negative breast cancer ; O'Shaughnessy J, Osborne C, Pippen JE, et al. N Engl J Med. 2011 Jan 20;364(3):205-14. Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Corkery B, Crown J, Clynes M, et al. Ann Oncol. 2009 May;20(5):862-7. Triple-negative breast cancer: Recurrence and survival. From Kim K, Lee E, Lee J et al.; Korea Breast Cancer Society. Clinicopathologic signature of TNBC patients with good prognosis. Paper presented at: San Antonio Breast Cancer Symposium (SABCS) 2009; December 15
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