1 / 45

Locally Advanced & Inflammatory Breast Cancer

Locally Advanced & Inflammatory Breast Cancer. Suparna Bonthala Wedam, M.D. National Cancer Institute Cancer Therapeutics Branch November 17, 2003. Locally Advanced Breast Cancer. LABC. 10%-20% of newly diagnosed breast cancer Heterogeneous group of tumors Definitions vary

avari
Télécharger la présentation

Locally Advanced & Inflammatory Breast Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Locally Advanced & Inflammatory Breast Cancer Suparna Bonthala Wedam, M.D. National Cancer Institute Cancer Therapeutics Branch November 17, 2003

  2. Locally Advanced Breast Cancer

  3. LABC • 10%-20% of newly diagnosed breast cancer • Heterogeneous group of tumors • Definitions vary • Stage IIB, IIIA, IIIB, and IIIC per AJCC 2002 staging guidelines (TNM staging classification) • No standard treatment regimen

  4. LABC • Large tumors (>5cm) • Extensive regional lymph node involvement • Direct involvement of the skin or underlying chest wall • No distant metastases • Inflammatory breast cancer

  5. Clinical Staging • Complete physical exam • Bilateral mammography • Blood tests • Complete blood count • Liver function tests • Radionuclide bone scan • Chest radiograph • CT scan of the abdomen and pelvis

  6. LABC Treatment • Historically considered inoperable • Distant metastases most frequent site of therapy failure with local therapy alone • 5 yr OS<20% • Adjuvant therapy-modest effect on survival • Primary chemotherapy has high response rates and increases rate of BCT • Multimodality treatment • Subsequent sequence of treatment unclear

  7. Primary ChemotherapyAdvantages • Early systemic treatment • Intact tumor vasculature • In vivo assessment of response • Decrease radical local therapy • Downstaging • Increase breast conservation • Improve resectability

  8. Primary ChemotherapyDisadvantages • Delayed local treatment • May induce drug resistance • Large tumor burden • Only have clinical staging • May increase risk of surgical/XRT complications

  9. Serial biopsies to examine Tissue architecture and histology Tumor markers/oncogenes or growth factors Matrix/stromal environment Functional studies: Dynamic imaging Metabolic testing Comparing primary to metastasis response to therapy Primary ChemotherapyResearch Rationale

  10. NSABP B-18 Operable Breast Cancer Stratification • Age • Clinical Tumor Size • Clinical Nodal Status Operation AC x 4 + TAM if >50 yrs. AC x 4 Operation + TAM if >50 yrs.

  11. B-18 Eligibility and Patient Characteristics • Palpable, operable breast cancer: • T1,2,3 N0,1 M0 • 1506 patients eligible after randomization • 51.5 % under age 49 • 74 % clinically node negative • Tumor size: • 28% <= 2 cm (T1) • 59% 2.1-5 cm (T2) • 13% >5 cm (T3)

  12. B-18Clinical and Pathologic Breast Tumor Response to Preop Chemo (685 pts) pCR (63 pts) 9% 36% 4% cCR (249 pts) pNon-Inv (26 pts) 23% pInv (160 pts) cPR (296 pts) 43% cSD + cPD (140 pts) 20%

  13. B-18Lumpectomy Rate P < 0.01 80% 60% 68% 60% 40% 20% 0 Preop Chemo Postop Chemo

  14. B-18Disease-Free and Overall Survival 100% 80% 60% P = 0.8 P = 0.5 Pts. Events Pts. Events 40% Postop 338 Postop 218 751 751 20% Preop 323 Preop 221 742 742 0 Year 2 4 6 8 2 4 6 8

  15. B-18Disease-Free and Overall SurvivalAccording to Response 100% 80% 60% pCR pCR pINV pINV P=0.0008 40% P=0.00005 cPR cPR 20% cNR cNR 0 Year 2 4 6 8 2 4 6 8

  16. B-18 Summary • Largest published trial comparing primary vs adjuvant chemo • Establishes primary and adjuvant chemo as EQUIVALENT for survival • No increased risk of local recurrence • Increased lumpectomy rate for primary chemo, esp for large tumors • Pathologic CR = better survival

  17. B-27 Schema Operable Breast Cancer Randomization AC x 4 Tam X 5 Yrs AC x 4 Tam X 5 Yrs AC x 4 Tam X 5 Yrs Surgery Docetaxel x 4 Surgery Surgery Docetaxel x 4 I II III Mamounas, Dec 2001

  18. B-27 Eligibility and Patient Characteristics • Palpable, operable breast cancer: • T1,2,3 N0,1 M0 • 2411 patients accrued • 56 % under age 49 • 70 % clinically node negative • Tumor size: • 15% <= 2 cm (T1) • 41% 2.1-4 cm • 45% >4 cm

  19. B-27Treatment Regimen AC: Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Taxotere: 100 mg/m2 Tamoxifen: In all patients, 20 mg PO daily X 5 years starting on day 1 of chemotherapy Breast XRT: In lumpectomy patients after surgery (Groups I and II) and after Taxotere (Group III)

  20. B-27Clinical Response*P<0.001 90.7%* 85.7% 85.4%

  21. B-27Pathologic Response in BreastP<.001 26.1%* 14.5% 12.9%

  22. B-27 Pathologic Nodal StatusP<.001

  23. AC Taxotere B-27Lumpectomy Rate P = 0.33 80% 60% 63.7% 61.6% 40% 20% 0 AC Bear et al, JCO, Nov 15 2003

  24. B-27 Conclusions The addition of preoperative Taxotere to preoperative AC resulted in a significant increase in the rates of: • Clinical Complete Response:40% vs 64%(p<.001) • Pathologic Complete Response:13.7% vs 26.1% (p<.001) • Negative Axillary Nodes:50.8% vs 58.2% (p<.001) Bear et al, JCO, Nov 15th 2003

  25. B-27 Conclusions (cont.) • There was an increase in grade 4 toxicity with the addition of Taxotere to the AC regimen • (10.3% vs 23.4%) • No significant increase in lumpectomy rates Bear et al, JCO, Nov 15th 2003

  26. Chemotherapy Regimens • AC • CAF • FEC, EC-mostly in Europe • CAF • CMF • CAVP • Combination or sequential regimens with taxanes (docetaxel, paclitaxel) • Clinical trials using trastuzumab (Herceptin)

  27. LABC Conclusions • Multimodality treatment • Prognosis based on certain factors • Age • Menopausal status • Tumor stage • Histologic grade • Clinical response • LN stats following tx • HR status • Approx 50% now attain long-term survival

  28. Inflammatory Breast Cancer

  29. Inflammatory Breast Cancer • Rare, 1-5% in U.S. • Most aggressive form of breast cancer • Clinical diagnosis • diffuse erythema involving majority breast • peau d’ orange • erisypeloid edge • often no palpable mass • Significantly lower overall survival than non-IBC

  30. Inflammatory Breast Cancer • Dermal lymphatic invasion • Stage IIIB (T4d) if not metastatic • Compared to non-IBC, more frequently ER/PR negative Her2/neu positive

  31. Clinical Presentations of IBC

  32. Survival and Prognosis of IBC: Single Institution Experiences

  33. IBC Survival: NCI Experience 100 90 80 70 60 50 40 30 20 10 Non-Inflammatory Inflammatory 3 6 9 12 15 18 21 Years from On-Study Date

  34. Primary Chemotherapy Surgery RT Chemotherapy + Hormonal Therapy Inflammatory Breast CancerStandard Treatment

  35. Rationale for Primary Chemotherapy • Consideredinoperable • Tumor extension beyond visible erythema • Micrometastatic at diagnosis • Response used to guide therapy

  36. Local Therapy Issues • Surgery: Mastectomy or BCT? • Reconstruction: Immediate or delayed? • Radiation therapy

  37. Immediate vs Delayed Reconstruction Issues • Postoperative radiation interferes with cosmetic result • Probability of local recurrence • Wound closure of large mastectomy site • TRAM vs skin graft? • Psychological benefit worth risk? • Recommend: Delayed Reconstruction

  38. Radiotherapy • Post-mastectomy radiation to a dose of at least 5000 cGy • Supraclavicular nodal radiation and bolus • Bifractionated radiotherapy (MDACC, McNeese)

  39. IBC Summary • Aggressive, poor prognosis disease • Primary chemotherapy to best response • Mastectomy, chest wall radiation • Delayed reconstruction • Enrollment onto clinical trials should be encouraged, especially for: • Herceptin • High dose chemotherapy • Experimental agents

  40. Case Presentation • 43 y.o. premenopausal female presented with lump on inner quadrant of right breast • Right core biopsy-grade III infiltrating ductal carcinoma, ER-, PR-, Her-2 3+ • No other symptoms • No significant medical history • No medications

  41. Physical Examination • Right breast • Enlarged, erythematous, tender • Diffuse mass-difficult to measure • Palpable right axillary lymph node • No other abnormalities

  42. Staging Work-Up • Labs-normal except for elevation of ALT • Bone Scan-? Met focus in sternum, bilateral SI joint uptake • CT Scan-4x3.6 cm right breast mass, 1.3x0.9 supraclavicular LN, 2.7 x 1.6 cm right axillary LN; liver okay • MRI of breast-abnormalities in right breast; no sternal involvement • STAGE IIC

  43. Treatment • Primary chemotherapy with paclitaxel, carboplatin and Herceptin (TCH) for 5 cycles • Right MRM/ALND • 2 cm poorly diff IDC, negative margins, 5/28LN+ • ER-, PR-, Her-2 3+ • Adjuvant therapy with doxorubicin and cyclophosphamide (AC) for 4 cycles • XRT

More Related