乳腺癌局部治疗进展

1、会计学1乳腺癌局部治疗进展乳腺癌局部治疗进展Giuliano AE, McCall L, Beitsch PD, Whitworth PW,Blumencranz PW, Leitch AM, Saha S, Hunt K,Brennan M, Ballman KV, Morrow MPresented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007研究支持假说： 接受保乳术与辅助系统化疗的乳腺癌患者单纯接受SLND与 I、II级ALND相比能取得相近的局部区域控制率与生存期。Presented By Armando

2、Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007106例（27.4%）接受了ALND的患者在前哨淋巴结（SN）外找到阳性淋

3、巴结。Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By

4、Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano

5、 at 2016 ASCO Annual Meeting Abstract 1007Presented By Armando Giuliano at 2016 ASCO Annual Meeting Abstract 1007Presented By Elizabeth Mittendorf at 2016 ASCO Annual MeetingPresented By Elizabeth Mittendorf at 2016 ASCO Annual Meeting思考Howlader N， et al.: SEER cancer statistics review. Bethesda: Na

6、tional Cancer Institute, 19752008.Carmichael AE: Does local surgery have a role in the management of stage IV breast cancer? Eur J Surg Oncol 2003;29:20112019Cardoso F, ESMO Guidelines Working Group: Locally recurrent or metastatic breast cancer: ESMO clinical recommendations for diagnosis, treatmen

7、t and follow-up. Ann Oncol 2009;20 Suppl 4:1518.Surveillance, Epidemiology, and End Results(SEER) Program ().SEER*Stat Database: Mortality all COD, Aggregated with State, Total U.S. (19692010) , National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance System B

8、ranch, released April 2013. underlying mortality data provided by NCHS (www. /nchs).Ann Surg Oncol (2013) 20:28282834Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Atilla Soran, MD, MPH, FACS,Magge-Womens Hospital of UPMCVahit Ozmen, Serdar Ozbas, Hasan Karanlik, Mahmut Mu

9、slumanoglu,Abdullah Igci, Zafer Canturk, Zafer Utkan, Cihangir Ozaslan, Turkkan Evrensel,Cihan Uras, Erol Aksaz, Aykut Soyder, Umit Ugurlu, Cavit Col, Neslihan Cabioglu, Betul Bozkurt, Efe Sezgin, Ronald Johnson, Barry LemberskyPresented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Prese

10、nted By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005主要终点：评价手术切除原发肿瘤对女性IV期乳腺癌患者OS的影响次要终点：发病率、局部-区域疾病进展/复发、生活质量Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005纳入/排除标准：纳入标准：u 活检证实为原发乳腺癌u 现阶段分期为IV期乳腺癌u 年龄18岁u 原发乳腺肿瘤可手术完整切除u 具备足够的器官功能可耐受方案中设计的局部放疗与系统治疗排除标准：u 原发乳腺肿瘤不可手术完整切除，或伴

11、有迁延的感染、出血或坏死u 患者体质较差不能耐受局部放疗与系统治疗u 之前诊断有其他恶性肿瘤史（不包括皮肤基底细胞癌及皮肤鳞状细胞癌、宫颈上皮内瘤变u 妊娠期或哺乳期u 患者不适合进行足够的随访与无法完成知情同意条款Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005统计分析：1.经过对过去回顾性研究（2007年之前）的思考，认为假设两组间3年总生存绝对差异在18%（局部-区域手术组为35%，单纯系统治疗组为17%）。2.假设有10%的脱落率因失访而产生。3.生存分析使用95%的可信区间（=0.05）与90%的检

12、验效能（=0.9）的单侧log-rank检验，样本量估算需要271例患者经过随机分组。Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 10051.根据患者与主治医生的倾向/原发病灶侵犯程度选择接受保乳术（BCS）或乳房切除术。2.临床/活检判定区域淋巴结转移或SLN（+）需行腋窝淋巴结清扫术。3.必须达到切缘干净。4.保乳术（BCS）后需全乳放疗（WBRT）。5.乳房切除术后的放疗根据

13、疾病侵犯程度与该中心的实践经验。6.研究者判断是否行转移灶活检。7.经随机分组后，标准治疗（ST）组患者即接受化疗，手术组患者在完整切除原发肿瘤后接受化疗。8.所有激素受体（HR）阳性乳腺癌患者接受了内分泌治疗（HT）。9.c-erb B2阳性（IHC 3+阳性 或 FISH +）接受了曲妥珠单抗治疗。10. 给予双膦酸盐的治疗需根据临床医生的判断。11.对于远隔转移所在部位的相关治疗（手术或放疗）需根据研究者的判断。Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Presented By Atilla So

14、ran at 2016 ASCO Annual Meeting Abstract 1005Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Presented By Atilla Soran at 2016 ASCO Annual Meeting

15、Abstract 1005Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 10051.在36个月的随访中是否行原发乳腺肿瘤切除两组在生存率上相近。2.更长的随访提示手术组患者的中位生存期（46个月 vs. 33个月；HR：0.66）与5年总生存率（41.6% vs. 24.4%）分别有统计学上的显著改善。3.罹患惰性MBC（如ER阳性、HER2 neu阴性、骨寡转移）与55岁以下的患者

16、人群能够从初始手术中得到显著的生存获益。4.初诊IV期乳腺癌患者中接受原发肿瘤切除不增加30天死亡率。5.标准治疗组的局部区域复发率是手术组的11倍（LRR：手术组 1% vs. 标准治疗组 11%）6.多发肝和/或肺转移可能提示初始手术预后不佳。Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005 转移性乳腺癌的生存较过去有明显改善，手术在原发肿瘤的处理中有重要的作用。 PS评分、年龄、伴随疾病必须纳入考量； 转移癌的肿瘤负荷需纳入考量； 手术的获益依靠对肿瘤的完整切除； 腋窝淋巴结清扫、局部-区域放疗应该纳入

17、考量，不管其转移如何。Presented By Atilla Soran at 2016 ASCO Annual Meeting Abstract 1005King TA, Lyman JP, Gonen M, Reyes S, Boafo C, Plichta J, Hwang ES, Rogu HS, Liu M, Boughey JC, Jacobs LK, Krontiras H, McGuire K, Storniolo A, Nanda R, Golshan M, Isaacs C, Meszoely IM, Van Poznak C,Babiera G, Norton L, Mo

18、rrow M, Wolff AC, Winer EP, Hudis CA转化性乳腺癌研究联盟Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006初诊IV期乳腺癌中手术对原发肿瘤处理的作用仍然存在很大争议。回溯性数据提示存在一致的生存获益：HR 0.69（0.63-0.77），p0.00001- 大部分证据为多模式治疗- 大部分证据中较少有ER阳性的肿瘤支持生存获益的前瞻性研究数据有限Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Prese

19、nted By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006 TBCRC 013：前瞻性注册研究描述近年来IV乳腺癌患者的特征- 对一线治疗的反应率- 接受原发肿瘤切除患者的比率- 手术决策的制定流程*与常见预后因素、手术、生存相关联的原发肿瘤分子学特征判定无法控制的局部病灶事件与姑息手术需要的频次完成相关肿瘤分子学层面研究*Presented at ASbrS 2016 Presented By Tari K

20、ing at 2016 ASCO Annual Meeting Abstract 1006纳入标准：-初诊IV期乳腺癌且原发肿瘤结构完整-在原发肿瘤行手术切除后3个月内确诊转移性乳腺癌-组织取自原发肿瘤与转移病灶入组时间：2009年7月2012年4月-共纳入127例合格的患者，14家中心，2个队列-队列A：初诊IV期乳腺癌且原发肿瘤结构完整的患者（n=112）-队列B：在原发肿瘤行手术切除后3个月内确诊为转移性乳腺癌的患者相关文献-Fackler MJ et al. Novel methylated biomarkers and a robust assay to detect circula

21、ting tumor DNA in metastatic breast cancer. Cancer Res 2014-King T et al. Prognostic impact of 21-Gene Recurrece Score in Patients with Stage IV Breast Cancer: TBCRC013. JCO 2016Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006 队列A的结果处理：112例初诊IV期乳腺癌且原发肿瘤结构完整的患者均由医生制定一线系统治疗方案对一线治疗出现反应者

22、（医生判定转移病灶的SD、PR、CR）可进入讨论行下一步选择性手术选择性手术在没有局部症状或需要局部控制的前提下完成患者与肿瘤的特征、对系统治疗的反应、原发肿瘤切除与3年OS之间的相关性使用log rank检验、K-M法、Cox回归进行生存分析。Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meetin

23、g Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 201

24、6 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented

25、 By Tari King at 2016 ASCO Annual Meeting Abstract 1006Presented By Tari King at 2016 ASCO Annual Meeting Abstract 1006 在这项前瞻性注册研究，初诊乳腺癌患者的3年总生存率为70%。 大部分患者（85%）的生存与接受的一线治疗及其反应率显著相关。 患者选择手术很可能是由于单个器官转移与即将接受一线化疗。 手术不对各个肿瘤亚型的生存都有影响。 HER2状态与患者年龄仍然是重要预后因素，需要更深入的研究确定能从手术中获益的患者亚群。 不应在临床研究外选择对原发肿瘤进行手术。Pres

26、ented By Tari King at 2016 ASCO Annual Meeting Abstract 1006| 64 对系统治疗有反应的患者中，对姑息手术的需求不常见，手术对其PFS并不是负面的影响，患者选择手术很可能是由于单个器官转移与即将接受一线化疗，需要更深入的研究确定能从手术中获益的患者亚群，不应在临床研究外选择对原发肿瘤进行手术。MF07-01 Vs TBCRC013指南证据：中国/NCCN指南/ABC2真实世界：IV期乳腺癌的特点 局部治疗的意义 人文关怀| 66 SLND的临床研究可以较好的指导临床治疗选择。 原发IV期乳腺癌的临床研究不易开展，来自于这些研究数据的结果指导临床需要权衡利弊慎重选择。系统治