Presentation on theme: "Neo-adjuvant Chemotherapy for Breast Cancer"— Presentation transcript:
1 Neo-adjuvant Chemotherapy for Breast Cancer Shiuh-Wen Luoh MD PhDPortland VA Medical CenterOregon Health Sciences University
2 Neoadjuvant Treatment of Primary BC Improve Surgical OptionsObtain Information on ResponseObtain Long Term Disease Free ControlJCO Vol 24, pp 1940-, 2006.
3 Neoadjuvant Treatment of Primary BC Caution on Future Trial Design! An increase in the pCR rate as the result of a Superior Treatment has not been proven to consistently translate into an Improved Long Term Outcome.Caution on Future Trial Design!JCO Vol 24, pp 1940-, 2006.
4 Recurrence Score in Predicting Response to Chemotherapy Recurrence Score (RS) from Genomic Health-- L Gianni JCO 23:7265-, Pre-OP AP/P-- S Paik JCO 24:3726-,2006 Adjuvant CMF-- J Chang ASCO 2006, abs # 538 Pre-OP TaxotereThird is the charm for RS?Publication Bias?ASCO 2006, Abs # 538
13 doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 each on day 1 every 14 days for 4 cycles with granulocyte colony-stimulating factor support (ADOC)versusdoxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 every21 days followed by docetaxel 100 mg/m2 every 21 days for 4 cycles (AC-DOC).Factors associated with a significantly higher breast-conserving surgery rate:pre-chemotherapy tumor size < 40 mm, non-lobular histological characteristics, treatment with AC-DOC, clinical response, post-chemotherapy tumor size < 20 mm, and treatment in a larger center (>10 enrolled patients).
26 A total of 143 neoadjuvant and 170 surgery-first patients were studied A total of 143 neoadjuvant and 170 surgery-first patients were studied. Patients treated with neoadjuvant chemotherapy were significantly more likely to have fewer than 10 lymph nodes retrieved at ALND than were the surgery-first patients (19/143 or 13% vs. 6/170 or 4%, P=003).
28 Neoadjuvant versus Adjuvant - A Meta-analysis JNCI Vol 97, pp 188-, 2005.
29 Neoadjuvant versus Adjuvant - A Meta-analysis JNCI Vol 97, pp 188-, 2005.
30 Neoadjuvant versus Adjuvant - A Meta-analysis Equivalent in Survival and Overall Disease Progression.Statistically Significant Increased Risk of Loco-Regional Relapse if RT without Surgery.“Trend Towards Increased Local Recurrence in B18!”(Multi-centric or Multi-focal Disease)JNCI Vol 97, pp 188-, 2005.
32 Evolving Role of Surgery and Radiationin the Pre-operative Systemic Therapy Setting- Morrow, Giuliano, HarrisExpert OpinionsUltrasound and FNA before Neoadjuvant therapy to assess Axillary LN statusFNA (+)-- Axillary Clearance after ChemotherapyPitfalls: 10-20% Error rate even in Best HandsDr. Morrow Recommends Sentinel Mapping pre-Chemo.Radiation Planning based on pre-treatment tumor features.ASCO 2006 Ticketed Session
33 Evolving Role of Surgery and Radiation in the Pre-operative Systemic Therapy Setting- Morrow, Giuliano, HarrisSurgical Options if Residual Tumor Present---Dr. Morrow Recommends:If Uni-focal tumor found with Negative Margin:Minimal Margin of 2 mm.If Multi-focal tumor found with Negative Margin:Further Surgery to Achieve as Wide Margin as Possible.ASCO 2006 Ticketed Session
38 Neoadjuvant Treatment of Primary BC Caution on Future Trial Design! An increase in the pCR rate as the result of a Superior Treatment has not been proven to consistently translate into an Improved Long Term Outcome.Caution on Future Trial Design!JCO Vol 24, pp 1940-, 2006.
39 Nodal Status post Neo-adjuvant Chemo is a Powerful Prognostic Factor - NSABP B-27 ExperienceJCO Vol. 24, pp , 2006.
40 Pathologic CR (pCR) post Neo-adjuvant Chemo is a Powerful Prognostic Factor - NSABP B-27 ExperienceJCO Vol. 24, pp , 2006.
41 Residual Cancer Burden (RCB) Measurement of Primary Tumor (size and cellularity) and Nodal Met (Number and Size)RCB-0 (pCR) to RCB-3Prognosis: RCB-0 = RCB-1 > RCB-2 > RCB-3ASCO 2006 Abs 536.
42 In vivo Sensitivity Directed Neoadjuvant Therapy -The Aberdeen Trial Locally Advanced or Large Primary (> 3 cM).162 Patients Completed 4 Cycles of CVAP52 Responders to get 4 More Cycles of CVAP (Group 1),52 Responders to get 4 Cycles of Taxetere (Group 2),55 Non-Responders to get 4 Cycles of Taxotere (Group 3).pCR: 16% (Gr 1); 34% (Gr 2); 2% (Gr 3).Improved BCS and 3 year Survival for Group 2.JCO Vol 20, pp 1456-, 2002.
43 In vivo Sensitivity Directed Neoadjuvant Therapy - The Gepartrio Trial TAC x2 to Select for Responders- >50% Size ReductionResponders to Complete TAC x6.Non-responders randomized to TAX x4 or NX x4.pCR in Responders after TAC x6: %;pCR in Non-responders after TAC x6: 7.3%;pCR in Non-responders after NX x4: 3.1%.More Effective Treatments Needed for Non-respondersAnnals Oncology Vol 16, pp 56- , 2005.
44 In vivo Sensitivity Directed Adjuvant Therapy - The M. D In vivo Sensitivity Directed Adjuvant Therapy - The M.D. Anderson ExperienceJCO Vol 22, pp , 2004.
45 In vivo Sensitivity Directed Adjuvant Therapy - The M. D In vivo Sensitivity Directed Adjuvant Therapy - The M.D. Anderson ExperienceJCO Vol 22, pp , 2004.
46 In vivo Sensitivity Directed Adjuvant Therapy - The M. D In vivo Sensitivity Directed Adjuvant Therapy - The M.D. Anderson Experience“What to do When There is Residual Disease?”JCO Vol 22, pp , 2004.
48 ILC Patients: 122 (12%) vs IDC Patients: 912 (88%). Invasive Lobular Carcinoma (vs Ductal)Older (53 y vs 47 y); More HR (+) (92% vs 62%); Lower Nuclear Grade and Higher Stage at Diagnosis.Less Likely to have pCR (3% vs 15%).Less Breast Conservation Surgery (16% vs 29%).Longer Recurrence Free and Overall Survival!!!JCO Vol. 23, pp 41- , 2005.
49 Invasive Lobular Carcinoma and Response to Neo-adjuvant Chemotherapy Single InstitutionPure ILC (n=118, 14%), Pure IDC (n=742, 86%).Lobular Histology- Older (53 y vs 49.6 y); Lower Grade; Larger Primary (T3: 38.1% vs 21.4%); More N0; More HR(+) (89% vs 60%).Mastectomy Rate: 70% (ILC) vs 52% (IDC).pCR: 1% (ILC) vs 9% (IDC).DFS at 60 month: 76.5% (ILC) vs 60.8% (IDC).OS at 60 month: 91.7% (ILC) vs 79.3% (IDC).
56 Neoadjuvant Treatment of Primary BC Candidate Selections as in Adjuvant Therapy -Avoid Over-treating.Endocrine Tx. for menopausal women unfit for chemo.Low pCR (1-8%) with Endocrine Tx.Higher pCR with HR(-) than HR(+).A Trial shows Endocrine and chemo comparable.Optimal Regimen or Duration not Established.Month of Endocrine Tx. or 4 Cycles of Chemo.Sentinel Node Mapping after Tx. Might be Reasonable.Marker Studies pre- and post- Tx.JCO Vol 24, pp 1940-, 2006.
57 SWOG 0012Locally Advanced and Inflammatory Breast CancerA60C600 q3w x 5 cycles vs. A24qw+ oral C60qd +G x 15wFollowed by Taxol 80 qw x 12w.372 Patients Enrolled, 265 evaluable. All Received MRM.FN: 1.8% and 0.6%. No Grade V Toxicity.More Hand Foot and Stomatitis with Continuous Chemo.pCR plus N0 is 26% versus 13% P=0.02.Highest PCR rate reported for LABC and IBC.SWOG 0221 is companion Adjuvant TrialS0012 and S0221 both closed due to poor accrual.ASCO 2006 LBA #537
59 Neo-adjuvant Dose Dense AC-Taxol A60C600 X 4cycles q2W followed by Taxol175 (N=34) or Taxotere (N=8) q2W.42 Patients (6IIA, 12IIB, 10IIIA, 5IIIB, 9IIIC).Grade III 19, ER(+) 18, HER-2(+) 8, Clinically N(+) 26.cCR plus cPR > 95%.pCR 33%(14/42) -- pCR 52.4% (HR-) versus 17.6% (HR+).Dose Dense AC-Taxol Safe, Efficient and High pCR Rate.SABC 2005 Abst #5062.
60 Docetaxel/Xeloda versus Adria/Cytoxan Neo-adjuvant Chemo for Stage II/III BCMature Result from a Randomized Phase III Trial.Positive Axillary Nodes by PET or FNA.A60C600 q3W X4 versus D75X(1000bid d1-14) q3W X4.209 Patients (Aug 02-April 05).Primary Tumor pCR DX (23%) versus AC (8%) p=More Hand-Foot Syndrome, Skin ∆ Mucositis with DX .SABC 2005 Abst #5052.