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Neo-adjuvant Chemotherapy for Breast Cancer

Neo-adjuvant Chemotherapy for Breast Cancer. Shiuh-Wen Luoh MD PhD Portland VA Medical Center Oregon Health Sciences University. Neoadjuvant Treatment of Primary BC Improve Surgical Options Obtain Information on Response Obtain Long Term Disease Free Control. JCO Vol 24, pp 1940-, 2006.

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Neo-adjuvant Chemotherapy for Breast Cancer

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  1. Neo-adjuvant Chemotherapy for Breast Cancer Shiuh-Wen Luoh MD PhD Portland VA Medical Center Oregon Health Sciences University

  2. Neoadjuvant Treatment of Primary BC Improve Surgical Options Obtain Information on Response Obtain Long Term Disease Free Control JCO Vol 24, pp 1940-, 2006.

  3. Neoadjuvant Treatment of Primary BC 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-, 2005 Pre-OP AP/P -- S Paik JCO 24:3726-,2006 Adjuvant CMF -- J Chang ASCO 2006, abs # 538 Pre-OP Taxotere Third is the charm for RS? Publication Bias? ASCO 2006, Abs # 538

  5. Predicting Residual Tumor Size is Difficult! M D Anderson Experience Annals of Surgery Vol. 243, pp 257- , 2006.

  6. 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) versus doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 every 21 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).

  7. Neo!Adjuvant Cancer 2006; 107:1459–66.

  8. 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).

  9. Cancer 2002;95:681–95.

  10. Neoadjuvant versus Adjuvant - A Meta-analysis JNCI Vol 97, pp 188-, 2005.

  11. Neoadjuvant versus Adjuvant - A Meta-analysis JNCI Vol 97, pp 188-, 2005.

  12. 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.

  13. Breast Cancer Vol. 13 No. 3. 2006

  14. Evolving Role of Surgery and Radiationin the Pre-operative Systemic Therapy Setting- Morrow, Giuliano, Harris Expert Opinions Ultrasound and FNA before Neoadjuvant therapy to assess Axillary LN status FNA (+)-- Axillary Clearance after Chemotherapy Pitfalls: 10-20% Error rate even in Best Hands Dr. Morrow Recommends Sentinel Mapping pre-Chemo. Radiation Planning based on pre-treatment tumor features. ASCO 2006 Ticketed Session

  15. Evolving Role of Surgery and Radiation in the Pre-operative Systemic Therapy Setting- Morrow, Giuliano, Harris Surgical 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

  16. Sentinel Node Mapping post Neo-adjuvant Chemo • NSABP B-27 Experience • ID rate: 85%; False (-): 10.7%; Only Node (+): 56%. JCO Vol. 23, pp 2694- , 2005.

  17. Neoadjuvant Treatment of Primary BC 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.

  18. Nodal Status post Neo-adjuvant Chemo is a Powerful Prognostic Factor - NSABP B-27 Experience JCO Vol. 24, pp 2019- , 2006.

  19. Pathologic CR (pCR) post Neo-adjuvant Chemo is a Powerful Prognostic Factor - NSABP B-27 Experience JCO Vol. 24, pp 2019- , 2006.

  20. Residual Cancer Burden (RCB) Measurement of Primary Tumor (size and cellularity) and Nodal Met (Number and Size) RCB-0 (pCR) to RCB-3 Prognosis: RCB-0 = RCB-1 > RCB-2 > RCB-3 ASCO 2006 Abs 536.

  21. In vivo Sensitivity Directed Neoadjuvant Therapy -The Aberdeen Trial Locally Advanced or Large Primary (> 3 cM). 162 Patients Completed 4 Cycles of CVAP 52 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.

  22. In vivo Sensitivity Directed Neoadjuvant Therapy - The Gepartrio Trial TAC x2 to Select for Responders- >50% Size Reduction Responders to Complete TAC x6. Non-responders randomized to TAX x4 or NX x4. pCR in Responders after TAC x6: 22.6%; pCR in Non-responders after TAC x6: 7.3%; pCR in Non-responders after NX x4: 3.1%. More Effective Treatments Needed for Non-responders Annals Oncology Vol 16, pp 56- , 2005.

  23. In vivo Sensitivity Directed Adjuvant Therapy - The M.D. Anderson Experience JCO Vol 22, pp 2294- , 2004.

  24. In vivo Sensitivity Directed Adjuvant Therapy - The M.D. Anderson Experience JCO Vol 22, pp 2294- , 2004.

  25. In vivo Sensitivity Directed Adjuvant Therapy - The M.D. Anderson Experience “What to do When There is Residual Disease?” JCO Vol 22, pp 2294- , 2004.

  26. Neo-adjuvant Chemotherapy Negative Receptor Status Predicts Higher pCR JCO Vol 24, pp 1940-, 2006.

  27. 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.

  28. Invasive Lobular Carcinoma and Response to Neo-adjuvant Chemotherapy Single Institution 1990-2002. Pure 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).

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