乳腺癌新辅助治疗临床思路PPT课件

乳腺癌新辅助治疗临床思路1Neoadjuvant of treatment for breast cancer2The first generationof neoadjuvant clinical trials - NSABP 18 3The second generation of neoadjuvant clinical trials-NSABP 274NSABP-B18/27Neoadjuvant vs adjuvant “AC”Rastogi et al JCO 20081, Neo-adjuvant=Adjuvant 2, pCR is a good surrogate marker for long-term outcome 3, NSABP-27 showed that the addition of preoperative taxanes to AC improve the response5Questionn In the second generation of neoadjuvant clinical,although addition of taxanes generally led to higher pCR rates, a clinically meaningful improvement in long-term outcomes was not shown consistentlyn early improvements in pCR rates cannot yet act as surrogate endpointsn most neoadjuvant trials undertaken so far have enrolled unselected populations of patients. 6Part :Proposal for the standard characterisation of the population to treatGianni L EW, Semiglazov V, et al. SABC 2008 (abstract 31/Leone JP et al.J Clin Oncol 27:15s, 2009 (suppl; abstr 625) Chang HR et al. J Clin Oncol 26: 2008 (May 20 suppl; abstr 604)the genomic complexity of breast cancer has started to be appreciated, with several subtypes with specific molecular profiles 7Subtypes by IHC-ASCO/CAP guidelines8Shanghai Breast Cancer Survival Study datasSu et al. BMC Cancer 2011, 11:292/1471-2407/11/2929HER2 positive4cycles Neo THLuminalB4cycles Neo XTTripe negative4cycles Neo TPPathology,IHCsubtypesLuminal A subtype： ER+ or PR +，HER2-,Ki6716%Luminal B subtype,Her2+:HER2+subtype： ER-PR-， HER2+TNBC： ER-、 PR-、 HER2-Neoadjuvant in BC - phase trial10Subtypes Luminal B HER2+ve TNBCregimes Capecitabine+Docetaxel Paclitaxel+Trastuzumab Paclitaxel+DDPnumbers 90 (42%) 90 (42%) 33 (16%)Median age 45 (26-69) 47 (26-76) 46 (29-66)绝经绝经 前前 64 (71.1%) 59 (65.6%) 22 (66.7%)绝经绝经 后后 26 (28.9%) 31 (34.4%) 11 (33.3%)Grade 1 17 (18.9%) 0 (0%) 0 (0%)2 61 (67.8%) 69 (76.7%) 19 (57.6%)3 12 (13.3%) 21 (23.3%) 14 (42.2%)Tumor size T1 9 (10%) 7 (7.8%) 4 (12.1%)T2 66 (73.3%) 58 (64.4%) 21 (63.6%)T3 9 (10%) 16 (17.8%) 4 (12.1%)T4 6 (6.7%) 9 (10.0%) 4 (12.2%)Node N0 45 (50%) 39 (43.3%) 18 (54.5%)N1 36 (40%) 40 (44.4%) 12 (36.4%)N2 5 (5.6%) 8 (8.9%) 1 (3.0%)N3 4 (4.4%) 3 (3.3%) 2 (6.1%)Stage II 71 (78.9%) 66 (73.3%) 25 (75.8%)III 19 (21.1%) 24 (26.7%) 8 (24.2%)213 patients (median follow up 24months)11Subtypes Luminal B HER2+ve TNBCRegimes XT TH TPnumber 90(42%) 90(42%) 33(16%)clinicalCR 19(21.1%) 47(52.2%) 14(42.4%)PR 52(57.8%) 36(40.0%) 14(42.4%)SD 18(20%) 7(7.8%) 5(15.2%)PD 1(1.1%) 0(0%) 0(0%)pathologypCR 13(14.4%) 39(43.3%) 11(33.3%)non-pCR 77(85.6%) 51(56.7%) 22(66.7%)Breast pCR 20(22.2%) 40(44.4%) 20(60.6%)Total pCR 29.6%(61/213)ORR 85.4%(182/213)Results12All patients6377Eligible with known HER2-status4387HER2 negative3060 HER2 positivew/o trastuzumab665HER2 positivewith trastuzumab662pCR454pCR119pCR181no pCR2606no pCR546no pCR481pCR-Rate*14.8%pCR-Rate*17.9%pCR-Rate*27.3%*ypT0 ypN0AGO13OS analysis by pCRArm N Eventspositive w trast 481 35positive w/o trast 546 75negative 2606 310No pCRArm N Eventspositive w trast 181 1positive w/o trast 119 9negative 454 14pCRn= 662 HER2+ with trastuzumabn= 3060 HER2 negativen= 665 HER2+; no trastuzumabLog-rankvs p=0.058vs p=0.134 vs p=0.295vs p=0.384 14n ClinicalT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n 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n 未进行分子分型的试验 8项，其中 5项新药试验， 3项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n 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15Part : Proposal for Use of the functional and molecular imagine as endpoint?n MRI-n Ultrasonography-n Mammography- n PET-CT-n MammographyIs controversial with respect to both assessment of disease extent and 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 method to investigate in the neoadjuvant setting at presenttends 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 pathologicaloutcome is poor, especially when calcifications are present. Results available on use of (FDG) PET-CT in the neoadjuvant setting are contradictory 16Part : Proposal for Use of the functionaland molecular imagine as endpoint?n PET CT-1 have shown that metabolic information obtained from FDG-PET provides 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 because 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, 20112, Duch J, et al. . Eur J Nucl Med Mol Imaging 2009; 36: 155157. 3, Straver ME, et al. Eur J Nucl Med Mol Imaging 2010; 37: 106976. 17StudyN = 71 patients N = 71 evaluablePET CT study71 patients before neo chemothearpy4 cycles neoOur PET imaging studyThe changes in the glucose uptake value should be associated with the tumors respond 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 18Characteristics of patients19Primary result- For all cases AUCFigure.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 95.1%, positive predictive value is 32.4%. 20The SUV decrease rate and tumor responseReceiver 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 0.453.21ROC curves of different subtypesA HER2: Area under curve: 0.679; Sensitivity: 0.500; Specificity: 0.857; 95% CI:0.370-0.987B Luminal A: Area under curve: 0.188; Sensitivity: 0.00; Specificity:0.375; 95% CI:0.00-1.00C Luminal B: Area under curve: 0.889; Sensitivity: 1.00; Specificity:0.778; 95% CI:0.353-0.916D Triple negative: Area under curve: 0.875; Sensitivity: 1.00; Specificity:0.750; 95%CI: 0.00-1.00 A BC D22Part : Proposal for Use of the functional and molecular imagine as endpoint?In our study-conclusions1. For PET CT, the metabolic response obtained on the end of neoadjuvant chemotherapy may be useful in determining histopathologic non-responders with high negative predictive value of 95.1%2. 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 functional and molecular imagine as the predicitive response for LuminalB /TNBC subtypes23Part :Proposal for the standard evaluation of the response to treatment1, PCRn An intermediate endpoint for breast cancer relapse and survival-To assess the pathological response to neoadjuvant treatment and to define PCR varies between clinical trials24Part :Evaluation of the response to treatment1, PCRNode- 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 significant difference in DFS and OS between PCR and residual DCIS25n III期、随机、对照试验，新辅助治疗n 样本量： 512n 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