Presentation is loading. Please wait.

Presentation is loading. Please wait.

Department of Surgery Inflammatory Breast Cancer Julie Lang, MD Assistant Professor of Surgery Director of Breast Surgical Oncology University of Arizona.

Similar presentations


Presentation on theme: "Department of Surgery Inflammatory Breast Cancer Julie Lang, MD Assistant Professor of Surgery Director of Breast Surgical Oncology University of Arizona."— Presentation transcript:

1 Department of Surgery Inflammatory Breast Cancer Julie Lang, MD Assistant Professor of Surgery Director of Breast Surgical Oncology University of Arizona Cancer Center

2 Department of Surgery Inflammatory Breast Cancer Rare, represents <6% of all breast cancers Most aggressive form of breast cancer Clinical diagnosis - red skin involving more than 1/3 of the breast - peau d’orange - often no mass lesion - thickened skin - edema of breast tissue - rarely ulceration is present - Pathologic diagnosis of invasive breast cancer required International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Annals of Oncology 2010

3 Department of Surgery Inflammatory Breast Cancer Clinical course - Onset in weeks to months rather than months to years - Often confused for an infection of the breast - Often patients see many physicians before correctly diagnosed - Usually have nodal metastasis at time of diagnosis - 30% have distant metastases at diagnosis

4 Department of Surgery Inflammatory breast cancer Clinical Stage III Tumor classified as T4D Prognosis worse than locally advanced breast cancer Tends to be diagnosed at a younger age than most breast cancer May be more prevalent in African Americans than Caucasians. More information needed on prevalence in other populations

5 Department of Surgery Prognostic Markers Often triple negative Higher frequency of HER2 amplification Elevated Ki67

6 Department of Surgery Inflammatory breast cancer Presenting Symptoms Redness100% Edema100% Clinically positive 63% axillary nodes Enlargement 43% Warmth 33% Nipple retraction 15% Induration 13% Pain or tenderness 8% Arm Edema 3% Haagensen et al, 1951-1980. Adapted from Swain, NCI

7 Department of Surgery Inflammatory Breast Cancer: Differential Diagnosis Mastitis or cellulitis Breast abscess Cellulitis post radiation Radiation dermatitis Duct ectasia

8 Department of Surgery

9

10 Locally advanced, non-inflammatory breast cancer

11 Department of Surgery Yang et al, BCRT 2007

12 Department of Surgery Yang et al, BCRT 2007

13 Department of Surgery Yang et al, BCRT 2007

14 Department of Surgery Inflammatory breast cancer: overall survival -398 patients treated at MDACC 1974-2005 -Median follow-up 5.8 years -236 deaths -Median overall survival 4.2 years -Increasing year not associated with decreased risk of death Gonzalez-Angulo et al, The Oncologist 2007

15 Department of Surgery Inflammatory breast cancer: recurrence free survival - 398 patients treated at MDACC 1974-2005 -Median follow-up 5.8 years -238 recurrences -Median recurrence free survival 2.3 years -Increasing year not associated with decreased risk of recurrence Gonzalez-Angulo et al, The Oncologist 2007

16 Department of Surgery Treatment of Inflammatory Breast Cancer Urgent need to start chemotherapy quickly Evaluate if surgical candidate, if so surgical treatment is modified radical mastectomy No role for SLN dissection No role for lumpectomy Comprehensive radiation therapy Consolidative chemotherapy

17 Department of Surgery What is the best treatment for IBC? 256 consective patients with IBC (non- metastatic) treated at MDACC 1977-2004 192 completed planned course of chemotherapy, MRM, post-mastectomy radiation, 64 did not. Bristol et al, Int J. Rad Onc Biol Phys 2008

18 Department of Surgery Bristol et al, Int J. Rad Onc Biol Phys 2008

19 Department of Surgery Bristol et al, Int J. Rad Onc Biol Phys 2008

20 Department of Surgery Bristol et al, Int J. Rad Onc Biol Phys 2008

21 Department of Surgery Bristol et al, Int J. Rad Onc Biol Phys 2008

22 Department of Surgery What is the best treatment for IBC? Univariate factors significant for locoregional control in the patients who completed treatment were: -Response to neoadjuvant chemotherapy -Surgical margin status -Number of involved nodes -Use of taxanes Bristol et al, Int J. Rad Onc Biol Phys 2008

23 Department of Surgery What is the best treatment for IBC? Increasing the total chest-wall dose of post-mastectomy radiation from 60 to 66 Gy significantly improved locoregional control for: - patients who experienced less than a partial response to chemotherapy - patients with positive, close, or unknown margins - patients < 45 years of age Bristol et al, Int J. Rad Onc Biol Phys 2008

24 Department of Surgery Genes associated with IBC “Basal-like” phenotype High levels of p53, MUC1, RhoC, E-Cadherin High levels of growth factor receptors such as HER2-neu and EGFR High levels of angiogenesis and lymphangiogenesis-related factors such as VEGF-A, VEGF-C, VEGF-D, FLT-1, KDR, Tie-1, Tie-2 Downregulation of p27kip1

25 Department of Surgery Chemotherapy Options Anthracycline containing regimen followed by a taxane (AC-T, FAC-T, FEC-T) Herceptin based regimens if indicated Lapatinib based regimens if indicated Hormonal based regimens if indicated Sutent? High dose chemotherapy with bone marrow transplant?

26 Department of Surgery Anti-angiogenesis Inhibitors Bevacizumab – monoclonal Ab VEGF Pilot neoadjuvant study in IBC clinical response rate 67% after single dose combined with doxorubicin/docetaxel Further studies necessary to determine if anti- angiogenesis inhibitors are clinically relevant approach in IBC Nature Reviews Clinical Oncology 2009

27 Department of Surgery Nature Reviews Clinical Oncology 2009

28 Department of Surgery Lapatinib Neoadjuvant Lapatinib + Paclitaxel in IBC 42 patients HER2 positive +/- EGFR positive 7 patients HER2 negative, EGFR positive Lack of efficacy in HER2 negative patients pCR rate 18%, clinical response rate 78% in HER2 positive patients Boussen et al, JCO 2010

29 Department of Surgery Radiation Therapy Accelerated hyperfractionated radiation to 66 Gy Local control 70-80% 70% of patients have localized disease at presentation Bristol et al, Breast Dis 2005

30 Department of Surgery IM nodes identified on US and CT pre-chemo post-chemo Courtesy of Dr Welela Tereffe, MD

31 Department of Surgery Locally advanced disease: Lateral Tangents + Medial Electrons Lateral TangentsMedial ElectronsIMN Courtesy of Dr Welela Tereffe, MD

32 Department of Surgery Initially positive IM nodes receive additional boost radiation Courtesy of Dr Welela Tereffe, MD

33 Department of Surgery Heart and lung exposure can actually be reduced by the use of an IMN field Courtesy of Dr Welela Tereffe, MD

34 Department of Surgery IBC Research Clinical trials help determine which treatments are most effective for breast cancer patients Rare form of cancer, many biological and treatment questions still unanswered An important area of disparities research

35 Department of Surgery One FDA-Approved Drug from Start to Finish 10 - 15 Years 1,000 - 6,000 Volunteers $1 billion Drug Development – Current Model

36 Department of Surgery It Is Time to Implement a More Efficient Clinical Trial Process Inefficient clinical trials account for a majority of the time and cost associated with the failures of the current system. We need to: Reduce time to conclusive results & accelerate learning Reduce patients/volunteers required Reduce cost of conducting trials Increase collaboration & data sharing

37 Department of Surgery Design Trials with the Future in Mind PRINCIPLESOLUTIONS Test agents where they matter most  Neoadjuvant setting, poor prognosis cancers  Integrate advocates into trial planning Rapidly learn to tailor agents  Adaptive Design  Neoadjuvant therapy  Integration of biomarkers, imaging Optimize Phase 3 trials  Graduate drugs with predicted probability of success in Phase 3 trials for given biomarker profile Drive Organizational Efficiency  Adaptive Design  Master IND  Test drugs by class, across many companies  Shared cost of profiling  Financial support separated from drug supply  Shared IT Infrastructure, caBIG Use Team Approach  Democratize access to data  Share credit and opportunity  Collaborative process for development

38 Department of Surgery One FDA-Approved Drug from Start to Finish 10 - 15 Years 1,000 - 6,000 Volunteers $1 billion Five FDA-Approved Drugs from Start to Finish 5.5 - 9 Years 1,000 - 3,000 Volunteers $200 Million Drug Development – I-SPY 2 Model 5 times more products for 1/5 of the cost (25 x improvement)5 times more products for 1/5 of the cost (25 x improvement) ½ of the time with ½ the volunteers (4 x improvement)½ of the time with ½ the volunteers (4 x improvement) 5 times more products for 1/5 of the cost (25 x improvement)5 times more products for 1/5 of the cost (25 x improvement) ½ of the time with ½ the volunteers (4 x improvement)½ of the time with ½ the volunteers (4 x improvement) 2 – 3 YEARS3 – 5 YEARS 0.5 – 1 YEAR 5 20 40 FIVE FDA- APPROVED DRUGS

39 Department of Surgery I-SPY 2 TRIAL Schema SURGERYSURGERY Tissue ONSTUDYONSTUDY MRI Biopsy Blood Draw MUGA/ECHO CT/PET Screening RANDOMIZERANDOMIZE Consent #2 Treatment Consent Paclitaxel* + Investigational Agent A (12 weekly cycles) AC (4 cycles) Paclitaxel * (12 weekly cycles) AC (4 cycles) Paclitaxel* + Investigational Agent B (12 weekly cycles) AC (4 cycles) MRI Biopsy Blood Draw MRI Blood Draw MRI Blood Draw *HER2 positive participants will also receive Trastuzumab. An investigational agent may be used instead of Trastuzumab. >= 2.5 cm Mammaprint high risk

40 Department of Surgery I-SPY 2 Participating & Candidate Sites

41 Department of Surgery Taxol + Trastuzumab* + New Agent A Taxol + New Agent C Patient is on Study Taxol + Trastuzumab Taxol + Trastuzumab* + New Agent B Taxol Taxol + New Agent E AC HER 2 (+) HER 2 (–) Randomize Surgery Learn and adapt from each patient as we go along Taxol + New Agent F Taxol + Trastuzumab* + New Agent C Taxol + New Agent D Taxol + New Agent GH Taxol + Trastuzumab* + New Agent F *Or equivalent MRI Residual Disease (Pathology) Key I-SPY 2 Adaptive Trial: Learn, Drop, Graduate, and Replace Agents Over Time

42 Department of Surgery I-SPY 2 Biospecimen Collection: Biospecimen Availability Blood (Serum, Plasma, Buffy Coat) Process & Distribute Samples to Labs Ship to I-SPY Lab Approved Biomarkers Per Protocol Qualifying Biomarkers Per Protocol Exploratory Biomarkers Per Protocol caTISSUE Shipping/Receiving, Quality information of Sample and Processed Sample caINTEGRATOR Assay Results H&E for % tumor Section Sample Process 1 core into FFPE Aliquot Sample Tissue (Core Bx, Section Frozen in OCT)

43 Department of Surgery Residual Cancer Burden

44 Department of Surgery 1.3 1.0 0 ∆S 1 S 0 S 0 PE = ∆S 1 ∆S 2 SER = S t1t1 t2t2 t0t0 S2S2 S1S1 ∆S 1 ∆S 2 S0S0 injection S0S0 S1S1 S2S2 SER map Washout SER>1.1 Plateau 0.9≤SER≤1.1 Gradual SER<0.9 ENHANCEMENT KINETICS: Primary Imaging Measurement: Tumor volume based on the Signal Enhancement Ratio (SER)

45 Department of Surgery MRI after full course of chemotherapy MRI after 1 cycle of chemotherapy MRI before chemotherapy Partial Response

46 Department of Surgery MRI before chemotherapy MRI after 1 cycle of chemotherapy MRI after full course of chemotherapy Complete Response

47 Department of Surgery Conclusions IBC has unique tumor biology from non-IBC Consensus exists on minimal diagnostic criteria HER2 targeted therapy effective in HER2 positive disease Given aggressive biology, these patients would benefit from clinical trial participation

48 Department of Surgery


Download ppt "Department of Surgery Inflammatory Breast Cancer Julie Lang, MD Assistant Professor of Surgery Director of Breast Surgical Oncology University of Arizona."

Similar presentations


Ads by Google