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Multidisciplinary Cancer Management Course




  Locally Advanced
Primary Breast Cancer
         Sandra Swain, MD
        ...
Multidisciplinary Cancer Management Course

          Natural History of Disease

• Most cases of stage III breast cancer ...
Multidisciplinary Cancer Management Course

                 Clinical Presentation
• “Grave clinical signs”
   –   Skin ul...
Multidisciplinary Cancer Management Course

        Clinical Presentation of
        Stage III Breast Cancer




         ...
Multidisciplinary Cancer Management Course

Clinical Presentation of Stage III, Locally
     Advanced (Inoperable) Disease...
Multidisciplinary Cancer Management Course

                Diagnostic Work-Up

• Distinguish benign from malignant diseas...
Multidisciplinary Cancer Management Course

                 TNM Staging System for
                 Advanced Breast Cance...
Multidisciplinary Cancer Management Course

         TNM Staging System for
      Advanced Breast Cancer (cont.)
N2   Invo...
Multidisciplinary Cancer Management Course

         TNM Staging System for
      Advanced Breast Cancer (cont.)
N3   Invo...
Multidisciplinary Cancer Management Course
          Stage Classifications for Locally
             Advanced Breast Cancer...
Multidisciplinary Cancer Management Course

      Stage Classifications for Locally
      Advanced Breast Cancer (cont.)

...
Multidisciplinary Cancer Management Course

Survival According to Treatment

                                             ...
Multidisciplinary Cancer Management Course

     Systemic Therapy for Breast Cancer
• Goals
  – Attain cure, prevent recur...
Multidisciplinary Cancer Management Course

       Chemotherapy for Breast Cancer

• Improves disease-free and overall sur...
Multidisciplinary Cancer Management Course

         Neoadjuvant Chemotherapy

• Concept developed concurrently with adjuv...
Multidisciplinary Cancer Management Course

    Neoadjuvant Chemotherapy (cont.)

• Goals
  – Decrease tumor size
  – Mini...
Multidisciplinary Cancer Management Course

           Clinical Rationale for
        Preoperative Chemotherapy
• Excellen...
Multidisciplinary Cancer Management Course

               Advantages of
         Neoadjuvant Chemotherapy
• Increased rat...
Multidisciplinary Cancer Management Course

    Factors Influencing Decision to Use
       Neoadjuvant Chemotherapy
      ...
Multidisciplinary Cancer Management Course
    NSABP B-18 Trial: Schema
          Operable Breast Cancer

                ...
Multidisciplinary Cancer Management Course
          NSABP B-18 Trial (cont.)
   Response to Preoperative Chemotherapy
   ...
Multidisciplinary Cancer Management Course

                       NSABP B-18 Trial (cont.)
                     Pathologi...
Multidisciplinary Cancer Management Course
                     NSABP B-18 Trial (cont.)
                      Rate of Lum...
Multidisciplinary Cancer Management Course

                             NSABP B-18 Trial (cont.)
                      Ip...
Multidisciplinary Cancer Management Course
                                         NSABP B-18 Trial (cont.)
             ...
Multidisciplinary Cancer Management Course

                                      NSABP B-18 Trial (cont.)
               ...
Multidisciplinary Cancer Management Course
            NSABP B-27 Trial: Schema
               Operable Breast Cancer
    ...
Multidisciplinary Cancer Management Course

           NSABP B-27 Trial (cont.)
       Effect of Preoperative Docetaxel
Co...
Multidisciplinary Cancer Management Course

         NSABP B-27 Trial (cont.)
     Effect of Postoperative Docetaxel

Comp...
Multidisciplinary Cancer Management Course
      NSABP B-27 Trial (cont.)
 Eligibility: Operable Breast Cancer
• Diagnosis...
Multidisciplinary Cancer Management Course

              NSABP B-27 Trial (cont.)
             Clinical Tumor Size at Ent...
Multidisciplinary Cancer Management Course

           NSABP B-27 Trial (cont.)
         Clinical Node Status at Entry

No...
Multidisciplinary Cancer Management Course

     NSABP B-27 Trial (cont.)
     Grade of Tumor at Entry

   Tumor          ...
Multidisciplinary Cancer Management Course
             NSABP B-27 Trial (cont.)
               Treatment Regimen
Chemothe...
Multidisciplinary Cancer Management Course

                      NSABP B-27 Trial (cont.)
                        Clinica...
Multidisciplinary Cancer Management Course
                        NSABP B-27 Trial (cont.)
                     Pathologi...
Multidisciplinary Cancer Management Course
                     NSABP B-27 Trial (cont.)
                   Histologically...
Multidisciplinary Cancer Management Course

                       NSABP B-27 Trial (cont.)
                     Histologi...
Multidisciplinary Cancer Management Course
NSABP Neoadjuvant Trial: Concept

         Operable Breast Cancer
         Core...
Multidisciplinary Cancer Management Course

        Neoadjuvant Docetaxel Trial
        by Aberdeen Breast Group
• Randomi...
Multidisciplinary Cancer Management Course

   Neoadjuvant Docetaxel Trial (cont.)
First Phase                            ...
Multidisciplinary Cancer Management Course

      Neoadjuvant Docetaxel Trial (cont.)
      Patient and Tumor Characterist...
Multidisciplinary Cancer Management Course

Neoadjuvant Docetaxel Trial (cont.)
   Response Rates: First Phase

          ...
Multidisciplinary Cancer Management Course
  Neoadjuvant Docetaxel Trial (cont.)
   Response Rates: Second Phase
      (Pa...
Multidisciplinary Cancer Management Course
  Neoadjuvant Docetaxel Trial (cont.)
   Response Rates: Second Phase
     (Pat...
Multidisciplinary Cancer Management Course

                             Neoadjuvant Docetaxel Trial (cont.)
             ...
Multidisciplinary Cancer Management Course
                          Neoadjuvant Docetaxel Trial (cont.)
                 ...
Multidisciplinary Cancer Management Course

   Update on Studies with Trastuzumab
• Survival advantage with chemotherapy a...
Multidisciplinary Cancer Management Course

                       Schema of Trials of
                    Neoadjuvant Tra...
Multidisciplinary Cancer Management Course
  Neoadjuvant Trastuzumab (cont.)
          Treatment Plan
                    ...
Multidisciplinary Cancer Management Course
      Neoadjuvant Trastuzumab (cont.): Pathologic Complete
                    ...
Multidisciplinary Cancer Management Course
    Neoadjuvant Trastuzumab (cont.)
Pathologic Complete Response by Hormone Rec...
Multidisciplinary Cancer Management Course

    Trials of Neoadjuvant Trastuzumab:
            Summary of Efficacy

• Preo...
Multidisciplinary Cancer Management Course

    Neoadjuvant Endocrine Therapy:
 Third-Generation Aromatase Inhibitors
    ...
Multidisciplinary Cancer Management Course

Efficacy of Neoadjuvant Endocrine Therapy




   Before treatment             ...
Multidisciplinary Cancer Management Course

                   Neoadjuvant Tamoxifen
                   Compared with Letr...
Multidisciplinary Cancer Management Course

                  Neoadjuvant Tamoxifen Compared with
                   Letro...
Multidisciplinary Cancer Management Course

Preoperative Endocrine Therapy: Tamoxifen
   Compared with Aromatase Inhibitor...
Multidisciplinary Cancer Management Course

     Radiation Therapy after Mastectomy

According to Consensus Statement deve...
Multidisciplinary Cancer Management Course




                 Prepared by

     Susana M. Campos, MD, MPH
        Dana-F...
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Locally Adv Breast Cancer

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Transcript of "Locally Adv Breast Cancer"

  1. 1. Multidisciplinary Cancer Management Course Locally Advanced Primary Breast Cancer Sandra Swain, MD Prof. of Medicine, Director of Washington Cancer Institute 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  2. 2. Multidisciplinary Cancer Management Course Natural History of Disease • Most cases of stage III breast cancer were once stage I breast cancer • In poor countries, more than half of patients have locally advanced or metastatic disease at the time of diagnosis – Lack of education – Lack of screening 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  3. 3. Multidisciplinary Cancer Management Course Clinical Presentation • “Grave clinical signs” – Skin ulceration – Skin edema – Tumor fixation to the chest wall – Axillary nodes larger than 2.5 cm – Fixed axillary nodes • Satellite skin nodules and infraclavicular, internal mammary, and supraclavicular adenopathy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  4. 4. Multidisciplinary Cancer Management Course Clinical Presentation of Stage III Breast Cancer Photographs courtesy of Aman Budzar and Henry Kuerer. Peau d’orange Large mass, edema, and erythema 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  5. 5. Multidisciplinary Cancer Management Course Clinical Presentation of Stage III, Locally Advanced (Inoperable) Disease Photographs courtesy of Frankie Holmes and Merrick Ross. Large primary breast cancer Locally advanced breast cancer 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  6. 6. Multidisciplinary Cancer Management Course Diagnostic Work-Up • Distinguish benign from malignant disease • Distinguish noninvasive from invasive disease • Obtain pathologic diagnosis before treatment – Percutaneous image-guided biopsy (preferred) • Core-needle biopsy • Fine-needle aspiration – Excisional biopsy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  7. 7. Multidisciplinary Cancer Management Course TNM Staging System for Advanced Breast Cancer T3 Tumor >5 cm T4 Invasion of the chest wall or to the skin (inflammatory breast cancer T4a Invasion of the chest wall T4b Edema, thickening of the skin, or ulceration of the skin or surrounding skin nodules T4c Signs of both T4a and T4b T4d Inflammatory cancer (breast is red, swollen, and warm) Greene FL, et al. AJCC Cancer Staging Manual, 6th ed, 2002. 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  8. 8. Multidisciplinary Cancer Management Course TNM Staging System for Advanced Breast Cancer (cont.) N2 Involvement of four to nine axillary lymph nodes or of internal mammary lymph nodes without axillary node involvement N2a Involvement of four to nine axillary lymph nodes N2b Involvement of only internal mammary lymph nodes 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  9. 9. Multidisciplinary Cancer Management Course TNM Staging System for Advanced Breast Cancer (cont.) N3 Involvement of 10 or more axillary lymph nodes or of the infraclavicular lymph nodes or of the internal mammary nodes with axillary node involvement N3a Involvement of 10 or more axillary lymph nodes or of the infraclavicular lymph nodes N3b Involvement of the internal mammary nodes and axillary nodes N3c Involvement of the supraclavicular nodes 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  10. 10. Multidisciplinary Cancer Management Course Stage Classifications for Locally Advanced Breast Cancer Stage IIB T2 N1 M0 T3 N0 M0 Stage IIIA T0 N2 M0 T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0 Singletary SE, et al. J Clin Oncol. 2002;20:3576-3577. 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  11. 11. Multidisciplinary Cancer Management Course Stage Classifications for Locally Advanced Breast Cancer (cont.) Stage IIIB T4 N0 M0 T4 N1 M0 T4 N2 M0 Stage IIIC Any T N3 M0 Stage IV Any T Any N M1 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  12. 12. Multidisciplinary Cancer Management Course Survival According to Treatment No. of 5-Yr. Treatment Patients Survival (%) Surgery only 2,453 36 Radiation only 2,386 29 Surgery plus radiation 4,249 33 Chemotherapy, surgery, 1,923 63 and radiation Giordiano SH et SH. Oncologist. 2003;8:521-530. Giordiano al. Oncologist. 2003;8:521-530. 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  13. 13. Multidisciplinary Cancer Management Course Systemic Therapy for Breast Cancer • Goals – Attain cure, prevent recurrence, eradicate micrometastases • Appropriate treatments – Tamoxifen or aromatase inhibitors for postmenopausal women – Ovarian ablation – Chemotherapy – Monoclonal antibody therapy – Supportive care 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  14. 14. Multidisciplinary Cancer Management Course Chemotherapy for Breast Cancer • Improves disease-free and overall survival • Durations of more than six months do not add major advantage • Anthracycline-based combinations are better than combination of cyclophosphamide, methotrexate, and fluorauracil (CMF) • Taxane-based combinations are more effective in the adjuvant setting • Trastuzumab in the adjuvant setting improves disease-free and overall survival 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  15. 15. Multidisciplinary Cancer Management Course Neoadjuvant Chemotherapy • Concept developed concurrently with adjuvant chemotherapy in the 1970s • Treatment for locally advanced breast cancer (stage III disease) • Allows for immediate assessment of tumor response • Allows for the evaluation of new and novel agents 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  16. 16. Multidisciplinary Cancer Management Course Neoadjuvant Chemotherapy (cont.) • Goals – Decrease tumor size – Minimize surgery – Establish tumor sensitivity • Appropriate treatments – Chemotherapy – Tamoxifen or aromatase inhibitors – Radiation therapy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  17. 17. Multidisciplinary Cancer Management Course Clinical Rationale for Preoperative Chemotherapy • Excellent response rates for locally advanced breast cancer • Efficacy of adjuvant chemotherapy for node- negative breast cancer • Equivalent survival for breast-conserving surgery and mastectomy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  18. 18. Multidisciplinary Cancer Management Course Advantages of Neoadjuvant Chemotherapy • Increased rate of breast-conserving surgery • Earlier treatment of micrometastases • Treatment serves as in vivo chemosensitivity assay • Improved rates of local control and disease-free survival 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  19. 19. Multidisciplinary Cancer Management Course Factors Influencing Decision to Use Neoadjuvant Chemotherapy in Operable Breast Cancer • Does the patient need adjuvant chemotherapy based on information known prior to surgery? • Would neoadjuvant chemotherapy potentially alter the extent of resection? • Does the patient desire breast preservation? • Would treatment benefit from knowledge of in vivo chemosensitivity? 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  20. 20. Multidisciplinary Cancer Management Course NSABP B-18 Trial: Schema Operable Breast Cancer Stratification • Age • Clinical tumor size • Clinical node status AC x 4 Operation + TAM if >50 yrs. AC x 4 + TAM if >50 yrs. Operation 5 – 6 April 2007 Wolmark et al. J Natl Cancer Inst Monogr. 2001;30:96-102. Cairo - Egypt South & East Mediterranean College of Oncology
  21. 21. Multidisciplinary Cancer Management Course NSABP B-18 Trial (cont.) Response to Preoperative Chemotherapy Complete response Clinical responses 9% (n = 63) Complete response (n = 249) 36% 4% Noninvasive disease (n = 26) 23% Invasive disease (n = 160) Partial response (n = 296) 43% Pathologic responses Stable and progressive disease (n = 140) 20% 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  22. 22. Multidisciplinary Cancer Management Course NSABP B-18 Trial (cont.) Pathologically Positive Nodes 80 P < 0.01 % positive nodes 60 40 58% 20 40% 0 Postop. Preop. chemotherapy chemotherapy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  23. 23. Multidisciplinary Cancer Management Course NSABP B-18 Trial (cont.) Rate of Lumpectomy 80 P < 0.01 60 % Lumpectomy 68% 40 60% 20 0 Postop. Preop. chemotherapy chemotherapy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  24. 24. Multidisciplinary Cancer Management Course NSABP B-18 Trial (cont.) Ipsilateral Breast Cancer Recurrence 30 Cumulative incidence (%) P = 0.11 20 Postop: 7.1 % Preop: 9.9 % 10 0 1 2 3 4 5 6 7 8 Year Wolmark et al. J Natl Cancer 6 April 2007 5 – Inst Monogr. 2001;30:96-102. Cairo - Egypt South & East Mediterranean College of Oncology
  25. 25. Multidisciplinary Cancer Management Course NSABP B-18 Trial (cont.) Survival 100 Disease-free survival (%) Overall survival (%) 80 60 P = 0.5 P = 0.8 40 Pts. Events Pts. Events Postop 751 338 Postop 751 218 20 Preop 742 323 Preop 742 221 0 2 4 6 8 2 4 6 8 Year Year Wolmark et al. J Natl Cancer Inst Monogr. 5 – 6 April 2007 2001;30:96-102. Cairo - Egypt South & East Mediterranean College of Oncology
  26. 26. Multidisciplinary Cancer Management Course NSABP B-18 Trial (cont.) Survival According to Response 100 Overall survival (%) Disease-free survival (%) 80 60 pCR pCR 40 pINV pINV P = 0.0008 P = 0.00005 20 cPR cPR cNR cNR 0 2 4 6 8 2 4 6 8 Year Year Wolmark et al. J Natl Cancer Inst Monogr. 5 – 6 April 2007 2001;30:96-102. Cairo - Egypt South & East Mediterranean College of Oncology
  27. 27. Multidisciplinary Cancer Management Course NSABP B-27 Trial: Schema Operable Breast Cancer Randomization AC x 4 AC x 4 AC x 4 tamoxifen x 5 yrs. tamoxifen x 5 yrs. Tamoxifen x 5 yrs. Surgery docetaxel x 4 Surgery Surgery docetaxel x 4 I II III 5 – 6 April 2007 Bear et al. J Clin Oncol. 2003;21:4165-4174. Cairo - Egypt South & East Mediterranean College of Oncology
  28. 28. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Effect of Preoperative Docetaxel Compared with chemotherapy and surgery alone, chemotherapy and docetaxel followed by surgery led to increased rates of – Clinical response – Pathologic response – Downstaging of node disease – Lumpectomies 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  29. 29. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Effect of Postoperative Docetaxel Compared with chemotherapy and surgery alone, chemotherapy and surgery followed by docetaxel led to increased rates of disease-free and overall survival in subgroups of patients (according to nodes) 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  30. 30. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Eligibility: Operable Breast Cancer • Diagnosis by fine-needle aspiration or core biopsy • Palpable on physical examination (T1c-3 N 0, M 0 / T 1-3, N 1, M 0) • Movable in relation to chest wall and skin • Nodes of any size but not fixed to each other or to adjacent structures • No arm edema 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  31. 31. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Clinical Tumor Size at Entry Size of Tumor Preop. AC Preop. AC + Preop. AC + (cm) (% of Pts.) Preop. Postop. Docetaxel Docetaxel (% of Pts.) (% of Pts.) ≤2.0 15 15 14 2.1-4.0 40 40 41 ≥4.0 45 45 45 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  32. 32. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Clinical Node Status at Entry Node Status Preop. AC Preop. AC + Preop. AC + (% of Pts.) Preop. Docetaxel Postop. (% of Pts.) Docetaxel (% of Pts.) Negative 70 70 69 Positive 30 30 31 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  33. 33. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Grade of Tumor at Entry Tumor Preop. AC Preop. or Postop. Grade (n = 2,400) Docetaxel (n = 1,494) 1 22 15 2 50 40 3 13 16 4 10 24 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  34. 34. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Treatment Regimen Chemotherapy: doxorubicin, 60 mg/m2 cyclophosphamide, 600 mg/m2 Docetaxel: 100 mg/m2 Tamoxifen: 20 mg, orally, daily for five years (beginning on day 1 of chemotherapy) Radiation: Only for patients who had lumpectomy; done after surgery (arms I and II) and after treatment with docetaxel) (arm III) 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  35. 35. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Clinical Response 100 cCR 80 40% 65% cPR % of patients 60 cNR 85% 91% 40 45% P < 0.001 20 26% 14% 9% 0 AC (n = 1,502) AC + docetaxel (n = 687) 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  36. 36. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Pathologic Complete Response No tumor Noninvasive 30 P < 0.001 % of patients 20 18.7% 10 9.8% 13.7% 25.6% 3.9% 6.9% 0 AC AC docetaxel (n = 1,492) (n = 718) 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  37. 37. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Histologically Positive Nodes 80 60 P < 0.01 % of patients 40 48.5% 40.5% 20 0 AC AC docetaxel (n = 1,492 pts) (n = 718) 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  38. 38. Multidisciplinary Cancer Management Course NSABP B-27 Trial (cont.) Histologically Positive Nodes 80 According to Response P < 0.0001 60 % of patients 61% 59% 55% 40 45% 20 13% 0 pCR pINV cPR cSD cPD cCR 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  39. 39. Multidisciplinary Cancer Management Course NSABP Neoadjuvant Trial: Concept Operable Breast Cancer Core biopsy (biomarkers) Randomization AC x 4 AC x 4 docetaxel x 4 docetaxel + capecitabine X 4 Surgery 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  40. 40. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial by Aberdeen Breast Group • Randomized trial • Single-agent docetaxel compared with anthracycline-based polychemotherapy regimen • 145 patients • Large (>3cm) or locally advanced (T3, T4, Tx N2) breast cancer • No prior therapy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  41. 41. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial (cont.) First Phase Second Phase Final Assessment / Surgery docetaxel x 4 s e p on s All Patients o Re N Randomize CVAP X 4 Re docetaxel x 4 sp on se OR CVAP x 4 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  42. 42. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial (cont.) Patient and Tumor Characteristics Randomized Randomized Nonrandomized CVAP Docetaxel Docetaxel Mean age (yrs.) 51.71 52.56 52.78 Tumor stage (%) T2 42 40 29 T3 42 46 38 T4 17 14 33 Mean tumor 48.9 45.3 50.8 diam. (mm) 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  43. 43. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial (cont.) Response Rates: First Phase Objective % of Pts. Clinical Response (N =145) Overall 67 Complete 16 Partial 51 Stable disease 32 Progressive disease 1 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  44. 44. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial (cont.) Response Rates: Second Phase (Patients with Response) Objective CVP Docetaxel Clinical Response (N = 50) (N = 47) Overall 66 94* Complete 34 62 Partial (additional) 32 32 Partial (maintained) 30 6 Progressive disease 4 0 *p = 0.001 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  45. 45. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial (cont.) Response Rates: Second Phase (Patients without Response) Objective % of Pts. Clinical Response (N = 48) Overall 55 Complete 13 Partial 42 Stable disease 35 Progressive disease 10 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  46. 46. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial (cont.) Survival 1.0 • Patients who docetaxel responded to Survival probability CVAP .9 • Randomized to: p=0.05 docetaxel x 4 or CVAP CVAP x 4 .8 Log Rank Test • Survival increased in .7 docetaxel group 0 10 20 30 40 50 60 Time (mos.) 5 – 6 April 2007 Hutcheon et al. Breast Cancer Res Treat. 2003;79 Suppl 1:S19-24. Cairo - Egypt South & East Mediterranean College of Oncology
  47. 47. Multidisciplinary Cancer Management Course Neoadjuvant Docetaxel Trial (cont.) Clinical Responses and Type of Surgery 100 100 Docetaxel Docetaxel CVAP CVAP 80 80 % of patients % of patients 60 60 40 40 20 20 0 0 Conservation Mastectomy Complete Partial Overall Clinical Response Type of surgery Overall response rate Breast-conserving surgery Docetaxel: 94% Docetaxel: 67% CVAP: 66% CVAP: 48% P < 0.001 P < 0.01 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  48. 48. Multidisciplinary Cancer Management Course Update on Studies with Trastuzumab • Survival advantage with chemotherapy and trastuzumab in the metastatic setting • Trastuzumab in adjuvant setting produced spectacular results with 50% decrease in recurrence • Alternative approach is to introduce trastuzumab in the neoadjuvant setting, where response to therapy can provide an intermediate endpoint for the impact of trastuzumab on survival in early breast cancer 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  49. 49. Multidisciplinary Cancer Management Course Schema of Trials of Neoadjuvant Trastuzumab Induction chemotherapy (fluorouracil, epirubicin, cyclophosphamide) (every 3 wks. x 4) Assess Assess clinical Definitive pathologic ± Tamoxifen response response breast ± Radiation ↑↑↑ ↑↑↑ ↑↑↑ ↑↑↑ surgery (every wk. x 12) ♥ ♥ ↑ trastuzumab, 4mg/kg first wk.; ↑ trastuzumab 2mg/kg every wk.; ♥ left ventricular ejection fraction 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  50. 50. Multidisciplinary Cancer Management Course Neoadjuvant Trastuzumab (cont.) Treatment Plan P = paclitaxel, 225 mg/m2, 24-hr IV F F F F infusion every 3 wks. P P P P E E E E C C C C FEC = fluorouracil 500 mg/m2 IV, days 1 and 4 VS epirubicin 75 mg/m2 IV, day 1 only F F F F cyclophosphamide 500 mg/m2 P P P P E E E E IV, day 1 only, every 3 wks. C C C C + Trastuzumab 4 mg/kg IV day 1, then 2 mg/kg IV wkly 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  51. 51. Multidisciplinary Cancer Management Course Neoadjuvant Trastuzumab (cont.): Pathologic Complete Response Rates 95% CI (41%-87%) 95% CI (43%-84%) 70 P = 0.016 60 50 66.7% 65.2% 40 N = 18 N = 23 P+FEC alone 30 P+FEC + H 20 25% 26.3% 10 N = 16 N = 19 0 DSMB Reviewed Data Final Results 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  52. 52. Multidisciplinary Cancer Management Course Neoadjuvant Trastuzumab (cont.) Pathologic Complete Response by Hormone Receptor Status 70 60 70% N = 10 50 61.5% N = 13 40 P+FEC alone 30 P+FEC + H 20 25% 27.2% N=8 10 N = 11 0 Positive Negative 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  53. 53. Multidisciplinary Cancer Management Course Trials of Neoadjuvant Trastuzumab: Summary of Efficacy • Preoperative clinical responses observed – Overall response rate, 70% to 90% – Clinical complete response, 15% to 30% – Pathologic complete response, approximately 18% • Responses higher for patients with 3+ expression of HER2 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  54. 54. Multidisciplinary Cancer Management Course Neoadjuvant Endocrine Therapy: Third-Generation Aromatase Inhibitors N NC N N N O N Exemestane N NC CN Letrozole H3C CH H C CH3 3 3 O CN Anastrozole CH2 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  55. 55. Multidisciplinary Cancer Management Course Efficacy of Neoadjuvant Endocrine Therapy Before treatment After treatment with letrozole for three months 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  56. 56. Multidisciplinary Cancer Management Course Neoadjuvant Tamoxifen Compared with Letrozole • 55 centers in 16 countries R Tamoxifen 337 postmenopausal A S women with ER-positive 20 mg daily N U and/or PR-positive (n = 170) Adjuvant disease, not eligible for D R therapy at breast-conserving O G investigator’s surgery M E discretion Letrozole I R 2.5 mg daily Z Y (n = 154) E 4 months Eiermann W, et al. Ann Oncol. 2001;12:1527-1532. 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  57. 57. Multidisciplinary Cancer Management Course Neoadjuvant Tamoxifen Compared with Letrozole: Breast-Conserving Surgery 70 Letrozole Tamoxifen 60 p = 0.022 % of patients 50 40 30 20 10 61% 52% 29% 15% 45% 35% n=154 n=170 0 T2 >T2 Overall Tumor Stage Eiermann W, et al. Ann Oncol. 2001;12:1527-1532; Newman LA, et al. Ann Surg Oncol. 2002;9:228-234. 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  58. 58. Multidisciplinary Cancer Management Course Preoperative Endocrine Therapy: Tamoxifen Compared with Aromatase Inhibitors Study P024 IMPACT Semiglazov PROACT Drug(s) LET TAM ANA TAM ANA+ EXE TAM ANA TAM TAM Duration 16 wks. 12 wks. 16 wks. 12 wks. No. of pts. 154 170 113 108 109 36 37 163 151 Response 55 36 37 36 39 89 57 50 40 rate (%) BCS (%) 45 35 46 22 26 39 11 47 38 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  59. 59. Multidisciplinary Cancer Management Course Radiation Therapy after Mastectomy According to Consensus Statement developed by American Society for Therapeutic Radiology and Oncology (ASTRO) • Radiation therapy should be part of the treatment for stage III breast cancers and for disease that involves four or more lymph nodes • At a minimum, the chest wall and the supraclavicular fossa should be treated with doses of at least 50 Gy 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
  60. 60. Multidisciplinary Cancer Management Course Prepared by Susana M. Campos, MD, MPH Dana-Farber Cancer Institute 5 – 6 April 2007 Cairo - Egypt South & East Mediterranean College of Oncology
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