7. Worldwide Overview: Chemotherapy vs no chemotherapy, by age &ER, ratio of recurrence rates in years 0-4 Sir Richard Peto, SABCS, 2007 0.81 (0.05) 0.78 ( 0.08) 60-69 0.75 (0.05) 0.65 (0.07) 50-59 0.51 (0.06) 0.57 (0.07) <50 ER+ ER-poor Age
9. Worldwide Overview: Taxane vs no chemo: Age <50 Sir Richard Peto, SABCS, 2007 0.86 (0.05) 0.84 ( 0.04) Taxane vs Anthr. 0.46 (0.08) 2p>0.00001 Taxan vs no chem 0.38 (0.07) Multiplying 3 RR 2p<0.00001 0.81 (0.05) 0.84 (0.05) Anthr. Vs CMF 0.68 (0.05) 0.56 (0.05) CMF vs no chem BREAST CANCER MORTALITY rate ratio RECURRENCE rate ratio years 0-4 only
10.
11. 2 nd Versus 3 rd Generation Regimen: Differences in Relapse at 10 years (Adjuvant! 8.0) 2 nd Generation Regimen 3rd Generation Regimen
12. ER Neg ER Pos HER2 NEG HER2 POS HER2 is Predictive of Paclitaxel Benefit By Estrogen Receptor Disease Free Survival n = 1322 paclitaxel No paclitaxel paclitaxel No paclitaxel paclitaxel No paclitaxel paclitaxel No paclitaxel Years Hayes D.F., et al. N Engl J Med. 357:1496-506, 2007 n=390 (29%) n=144 (11%) n=703 (53%) n=79 (6%)
14. US Oncology: TC vs AC RANDOMIZE Doxorubicin 60 mg/m2 IV Day 1 Cyclophosphamide 600 mg/m2 IV Day 1 Every 21 days x 4 cycles Docetaxel 75 mg/m2 IV Day 1 Cyclophosphamide 600 mg/m2 IV Day 1 Every 21 days x 4 cycles
20. Effects of Bisphosphonates on Antitumor Activity in Preclinical Models Tumor-induced osteolysis Tumor cell proliferation and viability Metastatic behavior of tumor cells Activity of cytostatic drugs Angiogenesis Tumor burden in vivo
36. NSABP B-18 Stratification • Age • Clinical Tumor Size • Clinical Nodal Status + TAM if > 50 y AC x 4 + TAM if > 50 yrs. AC x 4 Operable Breast Cancer Operation Operation
40. Which tumors > 1, <5 cm definitely get chemotherapy (pre or post)? ++ ++ Node positive ++ ?? Node negative ER/PR both negative ER or PR positive
41. Which tumors > 1, <5 cm definitely get endocrine therapy (pre or post)? - ++ Node positive - ++ Node negative ER/PR both negative ER or PR positive
44. Probability of pathologic complete response (pCR) as a function of Recurrence Score Gianni, L. et al. J Clin Oncol; 23:7265-7277 2005 Gianni, L. et al. J Clin Oncol; 23:7265-7277 2005 doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) every 3 weeks x 3, followed by weekly paclitaxel (80 mg/m2) x 12.
50. pCR in The Neoadjuvant Model Would Have Predicted Trastuzumab Efficacy Journal of Clinical Oncology , Vol 23, No 16 (June 1), 2005: pp. 3676-3685
51. National Neoadjuvant Chemo Trials Nab-paclitaxel then AC Anthracycline then taxane-trastuzumab Docetaxel then AC FEC-75 then paclitaxel-trastuzumab Control Arm Adds new agent, support schedule “equivalence” Add sunitinib or not, AC first or second Locally advanced, Her-2 negative S0800 Adds and/or substitutes new agent Add carbo or not, add or substitute lapatinib Her-2 positive CALGB 40601 Adds new agents, data mines for predictive factors Add gemcitabine or capecitabine, add bevacizumab or not Palpable and operable cancer NSABP B40 Optimal scheduling, toxicity Paclitaxel-trastuzumab then FEC-75-trastuzumab Her-2 positive ACOSOG-Z1041 Concept Experimental Therapy Patient Population Trial Name
52. Diffusion MRI: Functional Diffusion Mapping Red – increase ADC Green – stable ADC Blue – decrease ADC
53. Schema Pre-Treatment Evaluation Baseline MRI Repeat Baseline MRI Chemotherapy A Post-Chemo A MRI Chemotherapy B Surgery Chemotherapy A Post-Chemo A MRI Chemotherapy B Post-Chemo B MRI Part One Part Two Pre-Chemo B MRI 10 patients 14 patients
54. Diffusion MRI, Interim Results cSD -2.40 -1.62 7 cSD -0.33 -0.23 5 cPR 1.40 1.04 4 cPR 1.75 1.14 2 cPR 1.61 1.02 1 after Part A only ±.05 null thresh ±.025 null thresh Case # Response % vol inc > 2.5%
55. Diffusion MRI Interim Results cPR, pPR cPR, pPR cPR, pPR cPR, pCR cCR, pCR after Parts A & B cSD -2.40 -1.62 7 cSD -0.33 -0.23 5 cPR 1.40 1.04 4 cPR 1.75 1.14 3 cPR 1.61 1.02 1 after Part A only ±.05 null thresh ±.025 null thresh Case # Response % vol inc > 2.5%