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`EXHIBIT 1
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`EXHIBIT 1
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`EXHIBIT 2
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`——PRQGA’\»I/I‘Re5:: III IINI'
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`SOCIETY OF
`
`CLINICAL
`
`.NCOLOGY
`
`éfii/IERICAN
`
`
`
`UNCL
`The Librarv - UC Berkeley
`Received on: Da~28—98
`American Society of Clinical
`Oncology. Meeting
`the
`._Annuai meeting of
`Amarimmh Smuiaty pf Cliniaal
`
`AMGKAN02733994
`
`

`

`THIRTY-FOURTH
`
`Annual Meeting of the
`
`American Society of Clinical Oncology
`
`May 16 — 19, 1998
`
`PROGRAM/PROCEEDINGS
`
`Los Angeles, California
`
`
`
`ASCO Program Information
`iii
`Officers and Directors ...........................................................
`iv
`Calendarovaents ................
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`xi
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`CommitteeRosters....
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`xii
`General Information ..........................................................
`xvi
`Award Recipients ............................................................
`xvii
`1998 ASCO Merit Awards .......................................................
`xviii
`PlenarySession.
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`xix
`Integrated Symposia .........................................................
`xx
`Special Sessions ..................... .
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`xxiii
`Annual Business Meeting .....................................................
`xxiv
`Tumor Panel Sessions ............ .
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`Scientific Symposia ..................... .
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`EducationSessions ..............
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`Meet the Professor Sessions
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`1998Annual Meeting Support ........
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`1998ASCO Exhibitor List ....................... .
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`ASCO Shuttle Service .................... .
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`x1
`LosAngeles Convention Center Maps .......... .
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`xliii
`Scientific Program .........................................................
`xlv
`ASCOProceedings... ..............
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`1a
`PlenarySession ....................
`1a
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`Adult Leukemia and Lymphoma
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`2a
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`AIDS/Supportive Care .................... .
`41a
`Bone Marrow Transplantation/Cytokines ................. .
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`75a
`BreastCancer ........................
`97a
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`ClinicalPharmacology
`.V
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`185a
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`Gastrointestinal Cancer. .
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`255a
`GenitourinaryCancer ............ ..
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`307a
`GynecologicCancer ................
`349a
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`Head and Neck Cancer and CNS .....
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`Health Services .............................................. .
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`Immunobiology and Biologic Therapy ............................................. 428a
`LungCancer.
`.....
`.,4503
`MelanomaandSarcoma....r...._...
`................ .................__.505a
`Pediatric Oncology .......................................................... 525a
`Tumor Biology/Human Genetics ......
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`AMGKAN02733995
`
`

`

`1998 ASCO CALENDAR OF EVENTS
`
`SATURDAY, MAY 16, 1998
`
`Education Sessions
`8:00 aim-9:15 am
`
`E5
`Cancer Survivors: Clinical and Research Issues
`E8
`I-Tepntucullufur Carcinoma—Etiology. Pathogenesis and Ma nagement
`E13 Inhenmd Breast Gunter Susmptibility and Tufiting Prevention
`E15 Mnnugmncnt of Stage Ill Not-1~Stnal‘l Cell Lung Cancer
`E20 Prostate Cancer: What to do After Hormones Pail?
`E22 Rectal Cancer
`E24 Tumor Vaccines
`
`8:00 sum-9:15 am Meet the Professor Sessions
`
`M9A
`Identifying Patient}: at Risk for Cancel: Oluftm mflnyo Utopadc. M353
`M15A Management Trends in low and Intonnediate Risk Neuroblammn: Rnbarr Castleberry, MD
`M28A thimlar Cancer: Craig Nichols, MD
`M29A Therapy oi’Eale Stage Colorectal Cancer: Danim’ Haifa-1; MD
`
`
`8:00 ant-9:15 am Tumor Panel Sessions
`TPl Cutaneous Lymphoma
`TP3 Esophageal Carcinoma—Combined Modality Therapy
`
`9:35 am-10:50 an Education Session
`E6
`C-uritruversies in the Management of Early Stage Breast Cancer
`E7
`Germ Cell Tumors
`E9
`Hodgkin’s Disease
`E13
`inherited Breast Cancer Susceptibility and Testing Prevention
`E14 Interpreting Clinical Trials
`E16 New Agents for Colon Cancer
`E21 Psychosocial Interventions
`
`9:35 am-10:50 am Meet the Professor Sessions
`M2A
`Bioetatiatical Issues in Oncology Trials: Colin Begg. PhD
`M6A
`Ductnl Cnrc'mnma in Situ‘. Monica Morrow, MD
`M7A
`Endometrinl Chi-met: Jonathan Bowie, MD
`M12A Managumem of “win Metastases: Jay Steven Muffler. MD
`M14A Mnnageniem of Recurrent Into—Grade Lymphoma; Arm: Hofmri'nm: MD
`M17A Oatcngeneic Sm‘mmu: Robert Benjamin. MD
`M19A Ovarian Cancer: Molecules-Approaches to Management: Robert Bust, MD
`M23A Prostate Cantor: In“ Tanmck. MD
`M25A Rule nl’ Immunuflierapy in Renal Cancer: Ronald Bukaumat-i, MD
`M27A Solid Tumor [lying-enmity Jonathan Fletcher, MD
`
`Tumor Panel
`9:35 uni-10:50 am
`
`TPIO Thymoma
`
`Scientific Symposium
`9:35 am-10:50 am
`SS] Molecular Targets of Chemoprevention
`
`Internet Session
`9:35 tun-10:50 am
`
`181
`Introduction to the Internet and the World Wide Web
`
`11:10 uni-1:10 pm Presidential Symposium
`Report of the Task Force on End of Life Issues: Robert J. Mayer, MD—Chair
`
`
`2:10 pm-3:10 pm American Cancer Society Lecture
`Cancer Control Through Genetics: Opportunities and Challenges: Frederick Li, MD
`
`AMGKAN02733996
`
`

`

`SATURDAY, MAY 16, 1998 (CONTINUED)
`
`3:35 pm-4:50 pm Education Sessions
`
`E3 Alternative Donor Sources in Allogeneic Transplant
`E10 How to Break Bad News to Patients with Cancer
`E11 Implications of Genetic Rating for Practicing Physicians
`E17 New Approaches to the Treatment of Advanced Bladder Cancer
`E18 Non-Hodgkin's Lymphoma
`E19 Progress in Endocrine Tumors
`
`3:35 pm-4:50 pm Meet the Professor Sessions
`MlA Anal Cancer: James Marlenson, MD
`M5A
`Chronic Myelogenous Leukemia: Hagop Kantarjian, MD
`M10A Late Complications of Allogeneic Transplant: Keith Sullivan, MD
`M11A Management of Advanced Breast Cancer: Andrew Seiclman, MD
`M2OA Pain Management: Stuart Grossman, MD
`M22A Primary Extranodal Lymphomas—1998: Mary Gospodarowicz, MD
`M30A Treatment of Older Breast Cancer Patients: Hyman Muss. MD
`
`8:35 pm-4:50 pm Tumor Panel Sessions
`TPZ Early Stage Prostate Cancer
`TP4 Glioma—Adult and Pediatric
`TP5 Head and Neck Cancers
`TP7 Melanoma: Controversies in Advanced and Intermediate Risk Disease
`
`3:35 pm-4:50 pm Internet Session
`
`ISS Oncology on the Internet—Resources, ‘Ibols, and Trends for the Experienced
`Internet User
`
`3:35 pin-4:50 pm Special Sessions
`
`NCI Listens
`The Role of Consumers in Cancer Research and Clinical Trials
`
`8:00 am-9:15 am
`
`Education Sessions
`
`SUNDAY, MAY 17, 1998
`
`E1 Adult Acute Myeloid Leukemia
`E4
`Bone Metastases—Management
`E5
`Cancer Survivors: Clinical and Research Issues
`E8 Hepatocellular Carcinoma—Etiology, Pathogenesis and Management
`E15 Management of Stage III Non-Small Cell Lung Cancer
`E18 Non-Hodgkin’s Lymphoma
`
`8:00 urn-9:15 am Meet the Professor Sessions
`
`Childhood Acute Lymphoblastic Leukemia—Treatment of Relapse: David Poplack, MD
`MSA
`MlaA Management of Esophageal Cancer: Arlene Forostiere, MD
`MlGA Non-Small Cell Lung Cancer: Everett Vokes, MD
`M18A Outcomes Research and Management: Jane Weeks, MD
`M24A Resolving Ethical Dilemmas in Cancer Care: Ezekiel Emanuel, MD, PhD
`MZGA Small Cell Lung Cancer—Management Issues: David Johnson, MD
`
`
`
`8:00 am-9:15 am Tumor Panel Sessions
`
`TPl Cutaneous Lymphoma
`TP3 Esophageal Cancer Combined Modality Therapy
`'I‘Ptl Glioma—Adult and Pediatric
`
`
`
`8:00 am-9:15 am Scientific Symposia
`
`551 Molecular Targets of Chemoprevention
`332 Progress in Gene Therapy
`
`AMGKAN02733997
`
`

`

`SUNDAY, MAY 17, 1998 (CONTINUED)
`
`
`
`9:35 am-10:50 am Education Sessions
`
`Controversies in the Management of Early Stage Breast Cancer
`E6
`E9 Hodgkin's Disease
`E12 Incorporating Geriatric Principles into Oncology Practice
`E14 Interpreting Clinical Tnaln
`E16 New Agents for Colon Cancer
`E21 Psychosocial Interventions
`
`9:85 lam-10:50 am Meet the Professor Sessions
`
`
`Biostntisticul issue-s in Oncology Trials: C'm’in Boga, PhD
`M2B
`Chronic Lymphm‘ylic Leukemia. Michoe! GWLL'T, IVE)
`M4A
`Identifying Patients at Risk for Cancer: Olufunmilayo Olopade, MBBS
`M9B
`M15B Management Trends in Low and Intermediate Risk Neurublastoma: Robert Castleberry. MD
`M17B Osteogeneic Sarcoma: Robert Benjamin, MD
`M19B Ovarian Cancer: Molecular Approaches to Management: Robert Bast. MD
`M21A Pancreatic Cancer. Current and Futu ru Multimodality Treatment Strategies: Douglas Evans, MD
`M253 Role of lmmnnotherapy in Renal Cancer: firm Bujcmuski, MD
`M27B Solid Tumor Cytogenetics: Jonathan Fletcher, MD
`M283 'Ilasticular Cancer: Craig Nichols, MD
`M29B Therapy of Early Stage Colorectal Cancer: Daniel Holler; MD
`
`Tumor Panel Session
`9:35 aux-10:50 am
`
`
`'I‘P2 Early Stage Prostate Cancer
`
`Internet Session
`9:35 8111-10250 am
`182
`Introduction to the Internet and the World Wide Web
`
`
`
`9:35 sin-10:50 am Scientific Symposium
`SSB Viral Pathogenesis of Human Malignancies
`
`11:10 inn-12:25 pm
`
`Education Sessions
`
`E2 AIDS Associated Malignancies
`E4
`Bone Metastases—Management
`E23 Strategies for Promoting Evidence Based Medicine: Critical Appraisal, Prac‘ln'ce Guidelines and the Cochrane Collaboration
`E24 Tumor Vaccines
`
`11:10 am-12:25 pm Meet the Professor Sessions
`
`Ductal Carcinoma in Situ: Monica Morrow, All)
`M6B
`Endometria] Cancer: Jonathan Berek, MD
`M7B
`MBA Gastric Cancer: Update on Clinical Trials and Recent. Developments in Clinical Molecular Correlations:
`David Kuiocn, MD
`M12B Monagcmmn of Brain Metastases: Joy Strum Lilifmlfl'. MD
`M14B Management of Ramirrcnt Low-Gracie Lymphoma: Ame Rnhatiner; MD
`M22B Primary Extranodai Lymphomas—1998: Mary Gosporiarowicz, MD
`M233 Pronto LI: Cancel" for: ‘T‘armm‘Jc, MD
`
`Tumor Panel Sessions
`11:10 urn-12:25 pm
`-—————_.—._——._———_
`TPE Head and Neck Cancer
`TP'7 Melanoma: Controversies in Advanced and Intermediate Risk Disease
`TPB
`Sarcoma
`TP9
`The Clinical Challenge of Unknown Primary Tumors
`TPIO Thymoma
`
`
`
`11:10 aim-12:25 pm Scientific Symposium
`
`352 Progress in Gene Therapy
`
`
`
`11:10 aux-1:10 pm Special Session
`
`FECS/ASCO Symposium: Controversies and Challenges in the Management of Rectal Cancer
`
`V |
`
`AMGKAN02733998
`
`

`

`SUNDAY, MAY 17, 1998 (CONTINUED)
`
`
`Education Sessions
`1:25 pro-2:40 pm
`E2
`AIDS Associated Malignancies
`E3 Alternative Donor Sources in Allogeneic Transplant
`E10 How to Break Bad News to Patients with Cancer
`E12
`Incorporating Geriatric Principles into Oncology Practice
`E20 Prostate Cancer: \Vhat to Do After Hormones Fail?
`
`
`1:25 pm—2:40 pm Meet the Professor Sessions
`M4B
`Chronic Lymphocytic Leukemia: Michael Grever; MD
`MBB Gastric Cancer: Update on Clinical Trials and Recent Developments in Clinical Molecular Correlations:
`David Kelsen, MD
`Ml3B Management of Esophageal Cancer. Arlene Forastiere, MD
`MIGB Non-Small Cell Lung Cancer: Everett Votes, MD
`MIBB Outcomes Research and Management: Jane Weeks. MD
`M21B Pancreatic Cancer: Current and Future Multimodality Treatment Strategies: Douglas Evans, MD
`M24B Resolving Ethical Dilemmas in Cancer Care: Ezekiel Emanuel, MD, PhD
`MZSB Small Cell Lung Cancer—Management Issues: David Johnson, MD
`
`
`1:25 pm-2:40 pm
`Tumor Panel Session
`’I‘P6 Locally Advanced Cervical Cancer:
`Innovation and Treatment Optimization
`
`1:25 pin-2:40 pm Special Session
`
`International Symposium: Cancer Around the World
`
`1:25 pm-2:40 pm Scientific Symposium
`
`SSS Viral Pathogenesis of Human Malignancies
`
`
`3:20 pro—4:35 pm
`Education Sessions
`E1
`Adult Acute Myeloid Leukemia
`E7
`Germ Cell Tumors
`E11
`Implications of Genetic Testing for Practicing Physicians
`E17 New Approaches to the Treatment of Advanced Bladder Cancer
`E19 Progress in Endocrine Tumors
`E22 Rectal Cancer
`E23 Strategies for Promoting Evidence Based Medicine: Critical Appraisal, Practice Guidelines and the Cochrane Collaboration
`
`
`3:20 pm-4:35 pm Meet the Professor Sessions
`MIB
`Anal Cancer: James Martenson, MD
`M313
`Childhood Acute Lymphoblastic Leukemia—Treatment of Relapse: David Paplack, MD
`M5B
`Chronic Myelogenous Leukemia: Hagop Kantarjian, MD
`MlOB Late Complications of Allogeneic Transplant: Keith Sullivan, MD
`MIIB Management of Advanced Breast Cancer: Andrew Scidman, RID
`M2013 Pain Management: Stuart Grossman, MD
`M398 Treatment of Older Breast Cancer Patients: Hyman Muss, MD
`
`
`
`3:20 {rm-4:35 pm Tumor Panel Sessions
`
`TP6 Locally Advanced Cervical Cancer: Innovation and Treatment Optimization
`TPS Sarcoma
`TP9 The Clinical Challenge of Unknown Primary Tumors
`
`
`
`3:20 pm-4:35 pm Internet Session
`ISS Oncology on the Internet—Resources, Tools, and Trends for the Experienced Internet User
`
`
`4:00 pm-6:00 pm
`Integrated Session
`HER-2-Neu in Breast Cancer
`
`Special Sy'mposia
`4:55 pm-6:10 pm
`Forum on Reimbursement: Health Care Legislation, and Other Government Issues
`Strategies for Successful Clinical Grant Writing
`
`vii
`
`AMGKAN02733999
`
`

`

`MONDAY, MAY 18, 1998
`
`
`8:00 am-10:00 am
`Oral Sessions (Slide Sessions)
`Allogeneic BMT 8; Cytokjnes
`Cancer Genetics
`Cancer Vaccine Therapy
`Clinical Pharmacology
`Head and Neck
`Non—Hodgkin’s Lymphoma
`Non-Small Cell Lung,r Cancer
`Pediatric Oncology-Solid Tumors
`Progress in Early Breast Cancer
`
`8:00 am-10:00 am
`
`Poster Discussion Sessions
`
`HSR: Quality of Life and Clinical Trials
`Melanoma
`
`Integrated Symposium
`8:00 am-10:00 am
`Prostate Cancer: Optimizing Therapy for Different Disease Status
`
`8:00 8111-12200 pm Poster Discussion Sessions
`
`Clinical Pharmacology
`
`
`8:00 dim-12:00 pm
`General Poster Sessions
`
`Adult Leukemia/Lymphoma/Myeloma
`AIDS/Supportive Care
`Central Nervous System
`Clinical Pharmacology 1
`Gastrointestinal Cancer I—Upper GI, Pancreatic and Liver Cancer
`Gastrointestinal Cancer II—Colorectal Cancer
`Gene Therapy
`Gynecologic Cancer
`Sarcoma
`
`9:35 ant-10:50 am
`
`Internet Session
`
`
`
`183
`
`Introduction to the Internet and World Wide Web
`
`
`
`11:10 am-12:25 pm Internet Session
`
`IS7 Oncology on the Internet—Resources, Tools, and Trends for the Experienced Internet User
`11:15 sill-12:00 pm Special Session
`
`
`
`Karnofsky Award and Memorial Lecture: Cancer Pain—The Science. Politics. and Ethics, Kathleen Foley. MD
`
`1:00 pm-3:30 pm Plenary Session
`
`Plenary Session
`
`General Poster Sessions
`1:00 pin-5:00 pm
`Cancer Vaccines and Dendritic Cells
`Clinical Pharmacology 11
`Head and Neck Cancer
`Health Services Research
`
`
`3:45 pin-5:46 pm Oral Sessions (Slide Sessions)
`Advances in Breast Cancer Biology and Treatment
`Central Nervous System
`Melanoma
`Novel Compounds
`Pediatric Oncology—Leukemia/Ly‘mphoma
`Small Cell and Other Lung Issues
`'Iksticular Tumors
`
`W“
`
`AMGKAN02734000
`
`

`

`MONDAY, MAY 18, 1998 (CONTINUED)
`
`
`3:45 pm-5:45 pm
`Poster Discussion Sessions
`AIDS/Psychosocial
`Gastrointestinal Cancer
`Genetic Markers of Risk and Prognosis
`
`TUESDAY, MAY 19, 1998
`
`Oral Sessions (Slide Sessions)
`
`8:00 inn-10:00 am
`Sarcoma
`
`8:00 Inn-12:00 pm Oral Sessions (Slide Sessions)
`
`Gastrointestinal Cancer
`HSR: Economics. Guidelines, Outcomes and Patient Care
`Major New Treatment Issues in Gynecologic Cancer
`New Approaches in Drug Development
`Renal, Bladder & Prostate Cancer
`
`8:00 Inn-12:00 pm Poster Discussion Sessions
`
`Breast Cancer in Older Women
`Central Nervous System
`Cytokines, Minimal Residual Disease, and Conditioning Regimens
`Predictive Factors for Breast Cancer Treatment
`
`8:00 uni-12:00 pm General Poster Sessions
`
`Breast Cancer—Adjuvant Systemic Therapy
`Breast Cancer——General
`Breast Cancer—Local Therapy
`Clinical Pharmacology III
`Genitourinary Malignaucies
`Lung Cancer and Mesothelioma I—Diagnosis, Prognosis and Other
`Lung Cancer II—Non-Small Cell Lung Cancer Therapy
`Lung Cancer III—Small Cell Lung Cancer Therapy
`Metastases and Advanced Breast Cancer
`Pediatric Oncology I—Leukemia. Bone Marrow Transplant and Neuroblastuma
`Pediatric Oncology II—Lymphoma, Brain Tumors, and Other Pediatric Issues
`Tumor Biology and Cancer Genetics 1
`Tumor Biology and Cancer Genetics 11
`
`
`9:00 aim-11:00 am
`Oral Session (Slide Session)
`Anti-Emetics
`
`
`
`9:00 Inn-12:00 pm Oral Session (Slide Session)
`Hodgkin's Disease. Lymphoma and Myeloma
`
`Internet Session
`9:35 am-10:60 am
`
`1S4
`Introduction to the Internet and World Wide Web
`
`11:10 am-12:25 pm Internet Session
`
`ISS Oncology on the Internet—Resources, Tools, and Trends for the Experienced Internet User
`
`1:00 poi-3:00 pm Oral Session (Slide Session)
`
`Myelodysplasia and Leukemia
`
`IX
`
`AMGKAN02734001
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`

`

`TUESDAY, MAY 19, 1998 (CONTINUED)
`
`
`
`1:00 pm-3:00 pm Poster Discussion Sessions
`Genitourinary Cancer—Developing Approaches
`
`
`1:00 pm-5:00 pm
`Oral Session (Slide Session)
`’Ibpics in Breast Cancer
`
`
`
`1:00 pun-5:00 pm Poster Discussion Sessions
`
`Biochemical Pharmacology
`Small Cell, Non-Small Cell and Thoracic Surgical Issues Worth Discussing
`Gynecologic Cancer
`Head and Neck Cancer
`
`1:00 pm-5:00 pm
`
`General Poster Sessions
`
`Bone Marrow Transplantation/Cytokines
`Clinical Pharmacology IV
`Immunotherapy
`
`AMGKAN02734002
`
`

`

`980
`
`BREAST CANCER
`
`‘377
`ADDITION OF HEROEPTIN’Z" (HUMANIZED ANTI-HERZ ANTIBODY) TO FIRST LINE
`CHEMOTHERAPY FDR HERZ DVEREXPRESSING METASTATIC BREAST CANCER
`(HER2+IMBC) MARKEDLY INCREASES ANTICANCER ACTIVITY: A RANDOMIZED,
`MULTINATIONAL CONTROLLED PHASE III TRIAL D. Stamina, B. Leyland—Jones,
`S. Shak, V. Paton, A. Bajamonde, I Fleming, W. Eiermann, J. Walter,
`J. Base/go, L. Norton. Los Angeles CA, Montreal Canada, Genentcch, S.
`San Francisco, CA. Seattle WA. Munich Germany, Chicago IL, Barcelona
`Spain, New York NY.
`Herceptin (H), a humanized monoclonal antibody directed against HER2,
`has single-agent activity in previously-treated HER2+lMBC (JCO 14:737,
`1996). and is additive to chemotherapy (CRx)
`in HER2+ preclinical
`models. To test H's ability to augment the actiwty of CRx safely in the clinic.
`469 female patients (pts) with HER2+/M BC received doxorubicin-
`cyclophosphamide (AC) or paclitaxel
`(T) as first CRx if they had not
`received prior adjuvant A, or T if previously exposed to A. (A = 60 mglm’.
`C = 600 mglm2 , T = 175 mglm2 x 3 hrs, all CRx q 3 weeks X 6cycles)
`Half the pts (stratified by CRx) were randomized to additionally receive H (4
`mg/kg loading, then 2 ngkg intravenously q week). At a median follow-up
`of 10.5 months,
`investigator assessments of time to disease progression
`(TTP) and response rates (RR) show a significant augmentation of CRx
`effect by H, without increase in overall severe adverse events (AE):
`Enrolled
`'I'I'P(months)
`RR(%)
`AE(%)
`234
`5.5
`36.2
`66
`CRx
`235
`8.6‘
`62.0“
`69
`CRx + H
`145
`6.5
`42.1
`71
`AC
`146
`9.0
`64.9
`68
`AC + H
`89
`4.2
`25.0
`59
`T
`
`
`7.1 57.389T + H 70
`
`
`
`‘p < 0.001 by log-rank test ”p < 0.01 by X2 test
`A syndrome of myocardial dysfunction similar
`to that observed with
`anthracyclines was reported more commonly with AC + H (18% Grade 3/4)
`than with AC alone (3%), T (0%), orT + H (2%). Review by an independent
`Response Evaluation Committee and analysis of response duration, time to
`treatment failure, survival, and quality of life are in progress. In summary,
`these data indicate that addition of Herceptin to CRx markedly increases
`clinical benefit, as assessed by RR and TTP. Preliminary analySIs of both
`risk and benefit favors the regimen of Herceptin plus T.
`“"379
`FACTORS RESPONSIBLE FOR THE UNDERUTILIZATIDN OF BREAST CONSERVING
`THERAPY (BOT). M. Morrow, D.P. Winchester, JS. Chmiel, J. Moughan, J.
`Owens,
`T. Pajak, J. Sylvester and J.F. Wilson. Northwestern University
`Medical School, Chicago, IL
`Guidelines for BCT were developed in 1992 and widely disseminated. This
`study conducted by the American College of Surgeons and the American
`College of Radiology was undertaken to determine current patterns of care
`and to evaluate gUIdeIine adherence. 17,931 patients with Stage I and II
`breast cancer treated at 827 institutions in 1994 were studied. Only 7,914
`(44.1%) had BCT. 46.7% of BCT patients were under age 60 compared to
`40.7% of mastectomy patients (p < 0.0001). Significant differences in
`clinical and pathologic stage were noted between patients undergoing BCT
`and mastectomy, with 53.6% of 8,312 clinical stage I patients having BCT
`compared to 32.2% of 4.138 clinical stage II patients and 38.6% of 5,252
`patients with no clinical stage data (p < O 0001) Significant differences
`in prccedure were noted on the basis of both clinical tumor size and nodal
`status with 52.7% of 9,140 T1 tumors having BCT versus 32.6% of 3,954
`T2 tumors (p < 0.0001), and 47.2% of 11.435 NO patients versus 31.9%
`of 920 N+ patients having BCT (p < 0.0001). These differences persisted
`when pathologic stage was considered, with 51.4% of 9,662 pathologic
`stage I patients having BCT compared to 30.5% of 7,417 pathologic stage
`II patients (p < 0.0001) Patients with favorable histologies (tubular,
`mucinous,
`intracystic, n = 840) were more likely to undergo BCT than
`thosewith other histologies(n = 17.062; p < 0.0001). Radiotherapy (RT)
`was given to 78.6% of BCT patients. Of 1,155 patients not receiving RT,
`surgical failure to refer for RT accounted for 51 1%. and patient refusal for
`15%. These results indicate that surgeons continue to utilize BCT primarily
`for patients with favorable breast cancer,
`in spite of guidelines and data
`from randomized trials indicating that age, prognosis. and tumor type
`should not be used as selection criteria for local therapy. This misunderstand-
`ing is a maior factor responsible for low national rates of BCT.
`
`Proceedings of ASCO Volume )7 199B
`BREAST CANCER
`Progress in Early Breast Cancer
`Oral Session, Monday, May 18. 1998
`
`*378
`CIRCULATING INSULIN-LIKE GROWTH FACTOR | LEVEL AND RISK OF BREAST
`CANCER. Atl.llv;yfiofi{atr. W.C. Willett, G.A Colditz, D.J. Hunter, 0.3. Mi-
`chaud. B. Demo, 3. Rosner, F. E Speizer, S. E. Hankinson Charming
`Laboratory, Brigham and Women’s Hospital and Harvard Medical School
`(SEH, WCW. DSM, SAC, DJH. BR, FES); Departments of Epidemiology
`(SEH, WCW, DSM, GAC. DJH) and Nutrition (WCW, DSM), Harvard School
`of Public Health, Boston MA; Depts. of Medicine and Oncology, Lady Davrs
`Res Inst, of the JeWish General Hospital and McGill University, Montreal,
`Quebec. Canada.
`(lGF-l) is a mitogeriic and anti-apoptotic
`Insulin-like growth factor I
`peptide that
`influences the proliferative behavior of many cell
`types,
`including normal breast epithelial cells. To determine if higher circulating
`IGF-l
`levels are associated with an increased risk of breast cancer, we
`conducted a nested case-control study within the prospective Nurses'
`Health Study cohort. We examined plasma levels of lGF—l and lGF binding
`protein 3 (lGFBP-S), the major circulating lGF binding protein,
`in 397
`women with invasive breast cancer and 620 age-matched controls. We
`observed no appreCIable association between circulating IGF-1 and breast
`cancer risk among women who were postmenopausal at blood collection
`(top versus bottom quintile of IGF-1 level: relative risk (RR) = 0.85; 95%
`confidence interval (CI) = 0.53—1.39; p-trend = 0.63). However, among
`premenopausal women, particularly premenopausal women who were 50
`years of age or younger at blood collection. we observed a strong positive
`relationship (top versus bottom tertile comparison: among all premeno
`pausal women RR = 2.33. 95% CI = 1.06-5.16, p-trend = 0.08; among
`premenopausal women 50 yearsofage or less, RR = 4.58,95%C| = 1.75—
`12.0, p—trend = 0 02). These relative risks were somewhat stronger after
`accounting for plasma IGFBP-3 levels (RR = 2.88 and 7.28, respectively).
`These findings have potentially important implications both for identifying
`women at high risk of breast cancer and for the development of risk
`reduction strategies. Additional,
`larger studies of this association are
`needed to provide more precise estimates of the effect and to investigate
`the possibility of a relationship between premenopausal IGF-l levels and
`postmenopausal breast cancer risk
`
`
`
`‘380
`CURRENT MANAGEMENT OF AXILUIRY LYMPH NODES IN BREAST CANCER: A
`NATIONAL PATTERNS OF CARE STUDY. DR. Brenin, M. Morrow, J. Moughan,
`J. Owen, J.F. Wilson, and D.P. Winchester. Northwestern University Medical
`School, Chicago lL.
`Routine axillary lymph node dissection (ALND) for breast cancer patients
`has become controversial. Factors influencing the performance rates of
`ALND and axillary irradiation (Al) were evaluated in a joint study of the
`American College of Surgeons and the American College of Radiology.
`17,931 patients with Stage I and Il breast cancer treated at 827
`institutions in 1994 were studied. 15.992 (93.2%) underwent ALND The
`mean ages of patients who did and did not undergo ALND were 60.4yrs and
`73.0 yrs (p < 0.0001). Patients with Tla tumors underwent fewer ALND's
`when compared to patients with larger tumors (81% vs 93%, p < 0.0001).
`Patients with favorable histology (tubular, papillary and mucinous carcino
`mas) underwent ALND in 87 9% of cases, compared to 93.6% of patients
`with other histologies (p < 0 0001). Women age 70 or older underwent
`fewer ALND's compared to younger women (86% vs. 97%, p < 0.0001).
`Multivariate Analysis of ALND Rafe
`
`Odds Ratio (95% CI)
`p
`8.5 (6.3-11 4)
`0.0001
`5.4 (4.1—7.3)
`0.0001
`24(1 8—3 2)
`0.0001
`1 5 (1 0—2 2)
`0.04
`
`Mastectomy vs Lumpectomy
`Age <70 vs 270
`Stagele,T1cvsTla
`Non»favorable Histology
`
`ALND rate did not vary between palpable vs. non»pa|pable tumors nor with
`tumor grade. 899 patients received Al. Patients not undergoing ALND were
`more likely to receive Al (27% vs 12%, p < 0.0001).
`In patients who
`undenivent ALND, 1.6% of those with no lymph node metastasis received
`AI, 8 9% of those with 1—3 nodal metastases received AI, 24 0% of those
`with 4—9, and 29.9% of patients with 210 nodal metastases received Al
`We conclude that the majority of patients with small breast cancers
`continue to undergo axillary dissection while Al is under-utilized in patients
`at risk for local regional relapse.
`
`AMGKAN02734003
`
`

`

`EXHIBIT 3
`
`

`

`..nfl-_J\
`
`iasféiéafi-QH 993+. - i.
`-_ -_s_.A':1getes:CAw "
`— II
`
`AMGKAN02'733142
`
`

`

`
`
`Program/Proceedings
`of the
`
`American Society of Clinical Oncology
`
`Michael C. Pen'y, MD
`Program / Proceedings Editor
`
`
`American Society of Clinical Oncology
`
`Officers
`1997-98
`
`Robert J. Mayer, MD
`President
`
`Allen S. Lichter, MD
`Preside/t t-Elec!
`
`James O. Armitage, MD
`Im mediate Past President
`
`William P. Vaughan, MD
`Secretary! 'Il'easurcr
`
`Board of Directors
`
`Douglas W. Blayney, MD
`George J. 3051. MD
`Paul A. Bunn, Jr., MD
`Nancy E. Davidson. MD
`Jay R. Harris, MD
`Harry E. Hynes, MD. PhD
`John D. Minna, MD
`Larry Norton. MD
`Philip A. Pizza, MD
`J ames Lloyd Wade Ill, MD
`Barbara Lynn Weber, MD
`William C. Wood. MD
`
`John R. Durant, MD
`Exemlive Vice President
`———_—___—____
`
`Allan-act management and indexing provided by Prism Productions. Inc... Weslen'illo. 0H
`Elecrmnic pugpmnuumitiun and print urmlmliun nmvidi-d by WB Swindlers (lommny. Pliilmlolliliiu. PA
`and. the Muck Priming Gmup.
`
`Copyright 1995 b}: the American Society of Clinical Onmlogy
`
`AMGKAN02733143
`
`

`

`F820
`
`BREAST CANCER
`
`700
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`AMGKANO2'733144
`
`

`

`EXHIBIT 4
`
`

`

`Phase 11 Study of Weekly Intravenous Recombinant
`Humanized Anti-p185HER2 Monoclonal Antibody in
`Patients With HER2/neu-Overexpressing
`Metastatic Breast Cancer
`
`By José Baselga, Debasish Tripathy, John Mendelsohn, Sharon Baughman, Christopher C. Benz, Lucy Dantis,
`Nancy T. Sklarin, Andrew D. Seidman, Clillord A. Hudis, Jackie Moore, Paul P. Rosen, Thomas Twaddell,
`| Craig Henderson, and Larry Norton
`
`For use: Breast cancer lrequenlly overexpresses the
`panel a the HER2 photo-oncogene, a lflfirkd growth
`factor receptor [plBS’lmL The recombinant humanized
`monoclonal antibody (rhuMAb) HER2 has high affinity
`For p185”‘" and inhibits the growth of breast cancer
`cells that overexpress HER2. We evaluated the efficacy
`and toxicity at weekly intravenous administration of rhu-
`MAb HER2 in patients with HER2-overexpressing meta-
`static breast cancer.
`Patients and Methods: We treated 46 patients with
`metastatic breast carcinomas that overexpressed HER2.
`Patients received a loading close of 250 mg of intrave-
`nous rhuMAb HER2, then 10 weekly doses of 100 mg
`each. Patients with no disease progression at the comple-
`tion of this treatment period were olfered a maintenance
`phase of 100 mg/wk.
`
`Results: Study patients had extensive metastatic dis-
`ease, and most had received extensive prior anticancer
`therapy. Adequate pharmacakinetic levels at rhuMAb
`
`URLNG THE LAST DECADE, pinto—oncogenes that
`encode growth [actors and growth factor receptors
`have been found to play important roles in the pathogenesis
`of several human malignancies, including breast cancer.‘ The
`HER2 gene (also known as mm and as c-erbB—Z) encodes a
`lSS-kd transmembrane glycopmtein receptor (pl 85”") that
`has partial homology with the epidermal growth factor recep-
`tor. and that shares with that receptor intrinsic tyrosine kinase
`activity?“1 HER2 is overexpressed in 25% to 30% of human
`breast cancerss'6 and predicts for a worse prognosis in patients
`with primary disease that involves axillary lymph nodess'm
`Several litres of evidence support a direct role for HER2
`in the pathogenesis and clinical aggressiveness of HER2-
`overexpressing tumors: The introduction of HER2 into non—
`ncoplastic cells causes their malignant nansfonnation?“
`Transgenic mice that express HER2 develop mammary tu—
`mors.“ HER2 overexprcssion is common in ductal carcino-
`mas in situ and in their associated invasive cancers!“ Anti-
`
`bodies directed at 1318sz can inhibit the growth of tumors
`and of transformed cells that express high levels of this recep—
`[GEM-I8
`
`The latter observation suggests that p185“RZ may be
`a potential
`target for the treatment of breast cancer or
`preinvasive breast lesions because these cells commonly
`overexpress HER2. The murine monoclonal antibody
`(MAb) 4D5, directed against the extracellular domai