[教育]早期乳癌術(shù)后輔助化療

1、早期乳腺癌術(shù)后輔助治療,福建醫(yī)科大學(xué)附屬協(xié)和醫(yī)院 腫瘤內(nèi)科福建醫(yī)科大學(xué)腫瘤中心 腫瘤內(nèi)科組施純玫,內(nèi) 容,乳癌個體化治療研究臨床實踐-方案選擇,乳腺癌系統(tǒng)輔助治療取得的進展,,,,疾病相關(guān)復(fù)發(fā)風(fēng)險降低百分比,,,,,,0,10,20,30,40,,17%,,42%,46%,,31%,,CEF vs CMFLevine 2005,AC ? T vs ACHenderson 2003,Piccart 2005,三苯氧胺 vs 安

2、慰劑Fisher 2004,DAC vs FACMartin 2005,,28%,,,HER2+&HER2-,Romond 2005,,50,,52%,HER2+,化療+赫賽汀 vs 化療,化療 → 赫賽汀 vs 化療,,輔助治療方案選擇應(yīng)有循證醫(yī)學(xué)依據(jù),整體治療計劃 方案組成 劑量 療程 選擇與臨床試驗的入組條件最相近的方案,NCCN指南（英文版、中文版）St Gallen專家共識,INT C9741

3、 劑量密度 與 標(biāo)準(zhǔn)劑量中位隨訪5年,,C9741—DFS ： ER 狀態(tài)與劑量密集隨訪69個月,Disease-Free Survival,,0.0,,0.1,,0.2,,0.3,,0.4,,0.5,,0.6,,0.7,,0.8,,0.9,,1.0,,,,,,,0,,,1,,,2,,,3,,,4,,,5,,,6,,,7,Year,ER+ q3wk,ER- q3wk,ER- q2wk,ER+ q2wk,ER+ q2 n = 63

4、6 Events = 126 ER- q2 n = 336 Events = 99ER+ q3 n = 639 Events = 133 ER- q3 n = 327 Events = 127,P = .014,P = NS,ER = estrogen receptorsWith permission from Hudis C, et al. 2005 San Antonio Breast Cancer Symposiu

5、m. Abstract 41.,分子分型與病理免疫組化分型的大致關(guān)系,,WWW . Pnas.org/cgi/doi/10.1073/pnas.191367098,基因分型預(yù)后,ν,PAM 50 預(yù)測不同亞型生存率,Supervised Risk Predictor of Breast Cancer Based on Intrinsic SubtypesJoel S. Parker, Michael Mullins, Maggie J

6、 Clin Oncol 27:1160-1167,個體化治療時代,乳腺癌不是一種單一的疾病，而是一組生物學(xué)行為不同的疾病。術(shù)后輔助化療不再有“通用”的方案,È,,RANDOMIZE,tamoxifen x 5 yrs,Albain, et al. Breast Cancer Res Treat 2005,,,n = 1477,CAF x 6, then tamoxifen,,CAF x 6, with con

7、current tam,,(n = 361),(n = 550),(n = 566),SWOG 8814Postmenopausal N+ ER+,SWOG 8814/TBCI 0100 Sample Size for This Analysis,Patients with samples - 666 (45% of parent trial) RT-PCR obtained - 601 (90%)

8、Tamoxifen alone 148CAFT (concurrent)234CAF-T (sequential)219Final sample for primary analysis148 + 219 = 367 (40% of parent trial),,,,,,,,,,,,0.00,,0.25,,0.50,,0.75,,1.00,Disease-free survival,

9、,,0,,2,,4,,6,,8,,10,Years since registration,,,,Tamoxifen (n=55, 15 events),CAF-T (n=91, 26 events),Stratified log-rank p = 0.97 at 10 years,Low risk (RS < 18),Disease-Free Survival by Treatment,低RS者化療無受益,,,,,

10、,,,0.00,,0.25,,0.50,,0.75,,1.00,Disease-free survival,,,0,,2,,4,,6,,8,,10,Years since registration,,,,Tamoxifen (n=47, 26 events),CAF-T (n=71, 28 events),Stratified log-rank p = 0.033 at 10 years,High risk (RS

11、 ≥31),Disease-Free Survival by Treatment,,,,,,,,,,,0.00,,0.25,,0.50,,0.75,,1.00,Disease-free survival,,,0,,2,,4,,6,,8,,10,Years since registration,,,,Tamoxifen (n=46, 22 events),CAF-T (n=57, 20 events),Str

12、atified log-rank p = 0.48 at 10 years,Intermediate risk (RS 18-30),Disease-Free Survival by Treatment,高RS者化療明顯受益,RS與化療獲益的關(guān)系,,,,,,,,,0.00,,0.25,,0.50,,0.75,,1.00,Disease-free survival,,,0,,2,,4,,6,,8,,10,Years since regis

13、tration,,,,Tamoxifen (n=73, 36 events),CAF-T (n=112, 39 events),Stratified log-rank p = 0.011 at 10 years,HER2 Positive or ER Allred <7,,Her-2 - 和ER高表達(dá)者未能從CAF化療中獲益,根據(jù)ＴＮＭ分期,Panel of 21 Genes and the Recurrence

14、-Score Algorithm,S. Paik, NEMJ 2004,T 0.6-1cm（病理分化差、不良預(yù)后因素）或 T ＞1cm， N0 ER+ Her2 -,2007年St Gallen早期乳腺癌初始治療國際專家共識,低度危險：術(shù)后腋淋巴結(jié)陰性，并同時具備以下所有特征： pT≤2cm、病理分級1 級、未侵犯腫瘤周邊血管、HER-2(

15、-)、年齡≥35 歲。中度危險：① 腋淋巴結(jié)陰性，并至少具備以下特征中的一項：pT＞2cm、病理分級為2－3級、有腫瘤周邊血管侵犯、HER-2（+）、年齡＜35 歲 。② LNM 1－3 和HER-2(-)、HR（-）。高度危險：① 腋LNM 1－3 和HER-2 (+)、 ② 腋LNM>3。 2009年的共識加入了 Ki 67,內(nèi)分泌治療,適應(yīng)癥：所有激素受+PR+ ER － ：

16、意義未明，建議重新檢測免疫 組化ER－ PR －：病理類型較好的，如管樣癌、 膠樣癌，重新檢測免疫組化藥物選擇：,哪些患者無需化療，哪些患者需化療？,T＜1 cm、N0、無其他潛在復(fù)發(fā)風(fēng)險（脈管浸潤）者，可不給予任何全身治療，激素受體反應(yīng)型者可接受內(nèi)分泌治療。三陰性患者由于高復(fù)發(fā)風(fēng)險，絕大部分應(yīng)接受化療，而對于特殊類型乳腺癌如

17、髓樣癌（如診斷此型應(yīng)與病理科再次確認(rèn)，因典型髓樣癌極少見）、頂泌型癌及腺囊癌，由于其低危性可不接受化療，但若為三陰性患者也應(yīng)接受化療。,在選擇化療適應(yīng)證時對傳統(tǒng)的預(yù)后因子還應(yīng)予以充分的考慮，這些因子包括：淋巴結(jié)轉(zhuǎn)移、Ki 67（低表達(dá)＜15%，中表達(dá)15%～30%，高表達(dá)＞39%）、有絲分裂相高，年齡、脈管浸潤、Her-2 +、激素受體等，當(dāng)傳統(tǒng)的預(yù)后因子對指導(dǎo)化療無助時，多基因測定結(jié)果可作為參考因素之一。,哪些患者無需化療，哪些患者需

18、化療？,HR陽性 、Her-2陰性患者化療方案選擇,指南推薦方案,優(yōu)先采用方案,TAC、AC、劑量密集AC序貫紫杉醇、AC序貫每周紫杉醇、TC，,其他可選方案,FEC、CAF、EC、單周密集序貫A-T-C、CMF、EFC序貫單周紫杉醇,aBased on small subgroups of patients with HER2-positive breast cancer; bDDFS; CTx, chemothe

19、rapy; AC, doxorubicin, cyclophosphamide; P, paclitaxel; T, docetaxel; Carbo, carboplatin; V, vinorelbine; CEF, cyclophosphamide, epirubicin, 5-fluorouracil,Her-2 陽性者抗Her-2治療----- 赫賽汀治療持續(xù)無病生存獲益的研究,,3,4,5,4,Gianni et al

20、 2008; Gianni et al 2009; Joensuu et al 2009; Slamon et al 2006; Perez et al 2007;Smith et al 2007; Spielmann et al 2007,3,3,中位隨訪時間, 年,,,,DFS 獲益,B-31 / N9831 AC?PH,HERA 化療?赫賽汀 1 年,FinHera VH / TH?CEFb,PACS-04a CTx?H 1

21、 year,BCIRG 006 AC?TH,TCarboH,,,,,,n=231,n=528,NOAH CTx / H?H 1 year,3,,,,,,0,1,2,傾向赫賽汀治療,傾向非赫賽汀治療,HR,,,,1-年赫賽汀治療持續(xù)降低33％的死亡機會,0,1,2,,B-31 / N9831 AC?PH,3,HERA CTx?H 1 year,4,OS 獲益,BCIRG 006 AC?TH,3,TCarboH,3,傾向赫賽汀治療,傾向非赫

22、賽汀治療,HR,,,,,5,FinHer VH / TH?CEF,n=231,,,,中位隨訪時間, 年,,,,,Gianni et al 2009; Joensuu et al 2009; Slamon et al 2006; Perez et al 2007; Smith et al 2007,,,化療聯(lián)合赫賽汀,AC → THTCHDT →FEC使用時間1年監(jiān)測心功能,總 結(jié),個體化治療已步入臨床當(dāng)前建議將早期乳腺