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1、乳腺癌新辅助治疗临床思路,乳腺癌新辅助治疗临床思路,The first generation of neoadjuvant clinical trials - NSABP 18,The first generation of neoad,The second generation of neoadjuvant clinical trials-NSABP 27,The second generation of neo,NSABP-B18/27Neoadjuvant vs adjuvant “AC”,Rastogi et al JCO,1, Neo-adjuvant=Adjuvant,2, pCR
2、 is a good surrogate marker for long-term outcome,3, NSABP-27 showed that the addition of preoperative taxanes to AC improve the response,NSABP-B18/27Neoadjuvant vs ad,Question,In the second generation of neoadjuvant clinical,although addition of taxanes generally led to higher pCR rates, a clinical
3、ly meaningful improvement in long-term outcomes was not shown consistently early improvements in pCR rates cannot yet act as surrogate endpoints most neoadjuvant trials undertaken so far have enrolled unselected populations of patients.,QuestionIn the second generati,Part :Proposal for the standard
4、characterisation of the population to treat,Gianni L EW, Semiglazov V, et al. SABC (abstract 31/Leone JP et al.J Clin Oncol 27:15s, (suppl; abstr 625) Chang HR et al. J Clin Oncol 26: (May 20 suppl; abstr 604),the genomic complexity of breast cancer has started to be appreciated, with several subtyp
5、es with specific molecular profiles,Part :Proposal for the standa,Subtypes by IHC -ASCO/CAP guidelines,Subtypes by IHC -ASCO/CA,Shanghai Breast Cancer Survival Study datas,Su et al. BMC Cancer , 11:292biomedcentral/1471-2407/11/292,Shanghai Breast Cancer Surviva,HER2 positive4cycles Neo TH,LuminalB4
6、cycles Neo XT,Tripe negative4cycles Neo TP,Pathology,IHC,subtypesLuminal A subtype：ER+ or PR +，HER2-,Ki6716%Luminal B subtype,Her2+:HER2+subtype：ER-PR-，HER2+TNBC：ER-、PR-、HER2-,Neoadjuvant in BC - phase trial,HER2 positiveLuminalBTripe neg,213 patients (median follow up 24months),SubtypesLuminal BHER
7、2+veTNBCre,Results,SubtypesLuminal BHER2+ve TNBCR,All patients6377,Eligible with known HER2-status4387,HER2 negative3060,HER2 positivew/o trastuzumab665,HER2 positivewith trastuzumab662,pCR454,pCR119,pCR181,no pCR2606,no pCR546,no pCR481,pCR-Rate*14.8%,pCR-Rate*17.9%,pCR-Rate*27.3%,*ypT0 ypN0,AGO,Al
8、l patientsEligible with know,OS analysis by pCR,No pCR,pCR,n= 662 HER2+ with trastuzumab n= 3060 HER2 negative n= 665 HER2+; no trastuzumab,Log-rank vs p=0.134,vs p=0.384,OS analysis by pCRArmNEventspo,网站显示全球目前正在进行中的总共有15项乳腺癌新辅助化疗的III期临床试验其中有7项是基于分子分型的试验，受试对象为三阴性乳腺癌或HER2阳性乳腺癌未进行分子分型的试验8项，其中5项新药试验，3项
9、寻求验证新的分子标志物的指导意义的试验，1项研究双膦酸盐疗效的试验已经没有正在进行中的非基于分子分型的标准化疗的乳腺癌新辅助化疗临床试验,网站显示全球目前正在进行中的总共有15项乳腺癌新辅助化疗的I,Part : Proposal for Use of the functional and molecular imagine as endpoint?,MRI-Ultrasonography-Mammography- PET-CT- Mammography,Is controversial with respect to both assessment of disease extent and
10、 response to treatment. False-positive findings on breast MRI can arise after neoadjuvant chemotherapy. It could overestimate the extent of residual disease.Findings suggest that the value of MRI could be of particular importance for some BC subtype. MRI to be the most promising research imaging met
11、hod to investigate in the neoadjuvant setting at present,tends to overestimate residual tumour volume and, compared with mammography and MRI, it has the highest rate of false-positive findings and low specificity,specificity of mammography is low and prediction of pathological outcome is poor, espec
12、ially when calcifications are present.,Results available on use of (FDG) PET-CT in the neoadjuvant setting are contradictory,Part : Proposal for Use of th,Part : Proposal for Use of the functional and molecular imagine as endpoint?,PET CT-have shown that metabolic information obtained from FDG-PET p
13、rovides a reliable marker of tumour viability and treatment response, being associated with response to neoadjuvant chemotherapy at an early stage , and accurately visualising lymph-node metastases 2 Current guidelines do not support use of FDG-PET or FDG-PET with CT for staging of breast cancer bec
14、ause of the high false-negative rate for detection of lesions that are small (1 cm) or low grade, the relatively low sensitivity for detection of axillary nodal metastases,1, National Cancer Institute. Breast cancer treatment (PDQ). Nov 21, 2, Duch J, et al. . Eur J Nucl Med Mol Imaging ; 36: 155157
15、. 3, Straver ME, et al. Eur J Nucl Med Mol Imaging ; 37: 106976.,Part : Proposal for Use of th,StudyN = 71 patients,N = 71 evaluable,PET CT study71 patients before neo chemothearpy,4 cycles neo,Our PET imaging study,The changes in the glucose uptake value should be associated with the tumors respond
16、 to NAC, we conducted this retrospective study to investigate the value of PET imaging in the evaluation of respond to NAC in breast cancer.,histological diagnosis and subtype by IHC of breast cancer by core needle biopsy,StudyN = 71 evaluablePET CT st,Characteristics of patients,Characteristics of
17、patients,Primary result- For all cases AUC,Figure.1. The receiver operating characteristic curve of the overall predictive value of all the cases in the study. The area under curve is 0.697 , the sensitivity is 0.72, while the specificity is 0.674. 95% CI: 0.568-0.826, , negative predictive value is
18、 95.1%, positive predictive value is 32.4%.,Primary result- For all cases,The SUV decrease rate and tumor response,Receiver operating characteristic curve between SUV decrease rate and pathologic complete response. The AUC is 0.797 and reveals a sensitivity of 0.852 and specificity of 0.453.,The SUV
19、 decrease rate and tumo,ROC curves of different subtypes,C Luminal B: D Triple negative: Area under curve: 0.875; Sensitivity: 1.00; Specificity:0.750; 95%CI: 0.00-1.00,A,B,C,D,ROC curves of different subtyp,16 (17.Luminal B subtype：ER+ or PR +，HER2-,Ki6716%EDC方案对于特定患者可以显著提高pCR率绝经前biomedcentral/1471
20、-2407/11/292HER2 positiveHER2 positive1 (3.Capecitabine+Docetaxel18 (54.21 (63.Retrospective analysis of a database including 2302 patients with neoadjuvant chemotherapy at MD Anderson Cancer Center indicated no significant difference in DFS and OS between PCR and residual DCISPaclitaxel+DDPT400; Sp
21、ecificity:0.Eur J Nucl Med Mol Imaging ; 37: 106976.4 (12.HER2 positive,Part : Proposal for Use of the functional and molecular imagine as endpoint?In our study-conclusions,For PET CT, the metabolic response obtained on the end of neoadjuvant chemotherapy may be useful in determining histopathologic
22、 non-responders with high negative predictive value of 95.1% Different molecular phenotypes based on IHC reflect different metabolic properties . As our result, the luminal B subtype obtain a best predictive value, the less proliferation subgroup luminal A were the worst. 3. PET CT may be a good fun
23、ctional and molecular imagine as the predicitive response for LuminalB /TNBC subtypes,16 (17.Part : Proposal fo,90 (42%)Characteristics of patientsn= 3060 HER2 negativeFuture perspectives and conclusionsN = 71 evaluableTumor size T124 (26.69 (76.绝经前4 cycles neo9 (10%)Paclitaxel+DDP1, National Cancer
24、 Institute.Part :Evaluation of the response to treatment1, PCR31 (34.,Part :Proposal for the standard evaluation of the response to treatment 1, PCR,An intermediate endpoint for breast cancer relapse and survival-To assess the pathological response to neoadjuvant treatment and to define PCR varies b
25、etween clinical trials,90 (42%)Part :Proposal f,Part :Evaluation of the response to treatment1, PCR,Node- negative status after treatment have excellement survival-Retrospective analysis of a database including 2302 patients with neoadjuvant chemotherapy at MD Anderson Cancer Center indicated no sig
26、nificant difference in DFS and OS between PCR and residual DCIS,Part :Evaluation of the resp,III期、随机、对照试验，新辅助治疗样本量：512主要研究终点：pCR率,ABCSG-24 试验：主要研究终点的亚组分析,N=512分层因素： 月经状态 激素受体状态 组织学分级 HER2受体状态 研究点,6 x 表柔比星多西他赛,手术,HER2 (-),HER2 (+),HER2 (-),HER2 (+),曲妥珠单抗,安慰剂,6 x 表柔比星多西他赛卡培他滨,N=89,随机化,随机化,活检,Steger GG
27、, et al. ASCO Abst 530.,III期、随机、对照试验，新辅助治疗ABCSG-24 试验：,患者 (%),ED EDCpCR,EDC方案对于特定患者可以显著提高pCR率,Steger GG, et al. ASCO Abst 530.,经logist回归模型分析,无关临床淋巴结状态、停经状态以及HER2受体状态均可从EDC方案中获得一致的pCR,25 30 0 5 10 15 20患者 (%)E,Part :Evaluation of the response to treatment2, Ki-67,The standard cutoff for the value of
28、Ki67 as a response endpoint ?,Measurement of Ki 67,Part :Evaluation of the resp,Part :Evaluation of the response to treatment3 , Preoperative Endocrine Prognostic Index(PEPI),Predict long-term outcome (relapse-free/OS) in patients treated with neoadjuvant Endocrine therapy:Ki67 indexPathological tum
29、or sizeNodal statusER status,Part :Evaluation of the resp,Part :Standard evaluation of the response to the treatmentconclusion,Part :Standard evaluation of,Part :Standard definition of survival endpoint?- is lacking,STEEP system-standardised definition for efficacy endpointIssue:how to define the st
30、arting point for assessment of time-to-event data-DFS has been defined inconsistently either from the date of study entry or from the date of surgery-STEEP system in adjuvant setting, the starting point of these events,either the date of the first course of treatment, or the date surgery,Part :Stand
31、ard definition of,Systemic treatment pCR vs long-term outcomes in neoadjuvant,Systemic treatment pCR vs long,Future perspectives and conclusions,the neoadjuvant setting can be used for both therapeutic and research purposes, one can envisage a future in which neoadjuvant treatment could be recommend
32、ed to all patients eligible for adjuvant chemotherapy on the basis of their clinical and molecular characteristics. Further insights into understanding the mechanism of action of new drugs and identification of predictive and prognostic biomarkers could instead derive from implementation of biological window or other presurgical trials.,Future perspectives and conclu,Thank you!,乳腺癌新辅助治疗临床思路课件,谢谢观看！,谢谢观看！,
