National Institutes of Health Consensus Development Panel*
Correspondence to: John A. Bowersox, Communications Specialist, Office of Medical Applications of Research, National Institutes of Health, Bldg. 31, Rm. 1B03, Bethesda, MD 20892 (e-mail bowersoj{at}od.nih.gov).
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ABSTRACT |
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INTRODUCTION |
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Because of continuing research into new treatment methods, women with breast cancer now have more treatment options and a better chance of long-term survival than ever before. The primary treatment of localized breast cancer is either breast-conserving surgery and radiation therapy or mastectomy with or without breast reconstruction. Systemic adjuvant therapies that are designed to eradicate microscopic deposits of cancer cells that may have spread or metastasized from the primary breast cancer have been demonstrated to increase a woman's chance of long-term survival.
Systemic adjuvant therapies include chemotherapy (anticancer drugs) and hormone therapy. In addition to these systemic therapies, radiotherapy is used in selected cases as a local adjuvant treatment to destroy breast cancer cells that remain in the chest wall or regional lymph nodes after mastectomy.
The rapid pace of discovery in this area continues to expand the knowledge base from which informed treatment decisions can be made. The purpose of this conference was to establish a consensus regarding the use of adjuvant therapy for breast cancer and to communicate that consensus to clinicians, patients, and the general public. After reading relevant literature and attending a day and a half of presentations and audience discussion, an independent, non-Federal consensus development panel weighed the scientific evidence and drafted a statement that was presented to the conference audience on the third day. The Consensus Development Panel's statement addresses the following key questions:
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1) WHICH FACTORS SHOULD BE USED TO SELECT SYSTEMIC ADJUVANT THERAPY? |
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Prognostic and predictive factors fall into three categories: 1) patient characteristics that are independent of the disease, such as age; 2) disease characteristics, such as tumor size and histologic type; and 3) biomarkers (measurable parameters in tissues, cells, or fluids), such as estrogen receptor status, progesterone receptor status, and measures of cell turnover. Accepted prognostic and predictive factors include age, tumor size, axillary lymph node status, histologic tumor type, standardized pathologic grade, and hormone receptor status.
The median age for the diagnosis of breast cancer in women is between 60 and 65 years. Some younger women (particularly <35 years old) have a more aggressive form of the disease, characterized by larger tumors of higher grade with vascular invasion. Elderly women (>70 years old) with breast cancer frequently have hormone receptor protein in their malignant tissue, suggestive of a more indolent tumor pattern and a high likelihood of response to hormonal therapy.
Race appears to be a prognostic but not a predictive factor. In contrast to white women with breast cancer, black women with breast cancer are generally younger and often have larger tumors at diagnosis, and a smaller percentage of black patients have hormone receptors in their tumor tissue. These factors contribute to a poorer prognosis. In cases of similar clinical presentation, however, adjuvant treatment confers similar benefits to both black and white women. Research is needed on the benefits and risks of adjuvant therapy in Hispanic, Asian, and Native American women.
Novel technologies, such as tissue and expression microarrays and proteomics, present exciting potential, but their integration into clinical practice will depend on the proper design and analysis of clinical investigations. The same is true for measures of HER-2/neu overexpression or p53 status, histologic evidence of vascular invasion, and quantitative parameters of angiogenesis. These factors have been extensively studied both clinically and biologically, but they do not have an established role in patient management. For example, although overexpression/amplification of HER-2/neu is associated with an adverse outcome in lymph node-positive patients and may predict the response to therapy, laboratory methods and the reporting of results require standardization before its predictive performance can be established.
The development of immunohistochemical and molecular methods to identify occult cancer cells (i.e., micrometastases) in histologically tumor-free axillary lymph nodes or bone marrow has raised questions as to whether such findings should alter the clinical stage and become a further indication for systemic adjuvant therapy. At present, the clinical significance of these findings remains uncertain, and they require assessment in prospective clinical trials before they directly affect patient management.
It is essential that the value of predictive and prognostic factors be evaluated in well-designed clinical studies that are based on standardized protocols and have sufficient statistical power. Because these standards are infrequently met, very few new prognostic or predictive factors have been validated in the last 10 years, and future progress will depend on greater attention to these standards. Promising pilot studies should be followed by a validation phase, during which alternative assays for the biomarker are evaluated in a head-to-head comparison and prognostic/predictive value is studied. Since no single study will have sufficient power to properly evaluate predictive value, results from these trials should be combined.
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2) FOR WHICH PATIENTS SHOULD ADJUVANT HORMONAL THERAPY BE RECOMMENDED? |
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The goal of hormonal therapy is to prevent breast cancer cells from receiving stimulation from estrogen. Such stimulation occurs primarily in tumors that contain hormone receptor protein. Estrogen deprivation can be achieved by (a) blocking the receptor through the use of drugs, such as tamoxifen; (b) suppression of estrogen synthesis through the administration of aromatase inhibitors (e.g., anastrozole) in postmenopausal women or luteinizing hormone-releasing hormone agonists (e.g., goserelin) in premenopausal women; or (c) destruction of the ovaries through surgery or external beam radiation therapy. The administration of cytotoxic chemotherapy may indirectly accomplish this same effect by damaging estrogen-producing cells in the ovaries.
Adjuvant hormonal therapy should be recommended to women whose breast tumors contain hormone receptor protein, regardless of age, menopausal status, involvement of axillary lymph nodes, or tumor size. While the likelihood of benefit is related to the amount of hormone receptor protein in tumor cells, patients with any expression of hormone receptor in their tumor cells may still benefit from hormonal therapy. Such treatment has led to substantial reductions in the likelihood of tumor recurrence, second primary breast cancer, and death persisting for at least 15 years of follow-up. Possible exceptions to this recommendation include premenopausal women with tumors smaller than 10 mm who wish to avoid the symptoms of estrogen deprivation or elderly women with similarly sized cancers who have a history of venous thromboembolic episodes.
Tamoxifen is the most commonly used form of hormonal therapy. Randomized trials and a meta-analysis have shown that 5 years of tamoxifen are superior to 12 years of such treatment. Currently, there are no convincing data that justify the use of tamoxifen for longer than 5 years outside the setting of a clinical trial. Although tamoxifen has been associated with a slight but definite increased risk of endometrial cancer and venous thromboembolism, the benefit of tamoxifen treatment far outweighs its risks in the majority of women. Neither transvaginal ultrasonography nor endometrial biopsies are indicated as screening maneuvers for endometrial cancer in asymptomatic women taking tamoxifen. Tamoxifen may be combined with combination chemotherapy, particularly in premenopausal women; such combinations may further reduce the risk of recurrence. At this time, there are no data to support the use of raloxifene or aromatase inhibitors as adjuvant hormonal therapy.
For hormone receptor-positive premenopausal patients, alternative strategies of hormonal therapy, which are used far less frequently in the United States, include ovarian ablation through surgery, radiation therapy to the ovaries, or chemical suppression of ovarian function. Ovarian ablation appears to produce a similar benefit to some chemotherapy regimens. To date, adding ovarian ablation to chemotherapy has not been shown to provide an additional advantage. The value of combining hormonal therapies has not yet been explored adequately.
Hormonal adjuvant therapy should not be recommended to women whose breast cancers do not express hormone receptor protein. Randomized clinical trials have not yet shown that such treatment substantially reduces the likelihood of recurrence or, in the case of tamoxifen, diminishes the likelihood of contralateral breast cancer.
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3) FOR WHICH PATIENTS SHOULD ADJUVANT CHEMOTHERAPY BE RECOMMENDED? WHICH AGENTS SHOULD BE USED AND AT WHAT DOSE OR SCHEDULE? |
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Randomized clinical trials have attempted to define optimal chemotherapy regimens, doses, and schedules in the adjuvant treatment of breast cancer. These studies, along with the results of overview analyses, permit a number of conclusions to be drawn.
The administration of polychemotherapy (two or more agents) is superior to the administration of single agents. Four to six courses of treatment (36 months) appear to provide optimal benefit, with the administration of additional courses adding to toxicity without substantially improving overall outcome. However, definitive data on the benefits of more prolonged treatment are lacking, and future research is needed to address directly this clinically relevant issue.
Anthracyclines, such as doxorubicin and epirubicin, have been used as components of adjuvant polychemotherapy for breast cancer. Available data indicate that adjuvant chemotherapy regimens that include an anthracycline result in a small but statistically significant improvement in survival compared with non-anthracycline-containing regimens. There is no evidence for excessive cardiac toxicity in women without significant pre-existing heart disease treated with anthracyclines at the cumulative doses utilized in standard adjuvant programs. In clinical practice, the decision to use an anthracycline in an individual patient should take into consideration the potential survival benefits versus the specific concern about additional toxicity.
Randomized trials have demonstrated threshold dose effects for two of the most active chemotherapeutic agents, doxorubicin (A) and cyclophosphamide (C). These two drugs are frequently administered together (AC) and appear to result in a comparable survival outcome, whether given preoperatively or postoperatively. However, AC has not been compared with cyclophosphamide/doxorubicin/5-fluorouracil (CAF) or cyclophosphamide/epirubicin/5-fluorouracil (CEF). There is a need for future studies to address the issue of defining the optimal use of anthracycline-based therapy.
There is currently no convincing evidence to demonstrate that more dose-intensive treatment regimens (e.g., high-dose chemotherapy with peripheral stem cell support) result in improved outcomes compared with the administration of polychemotherapy programs at standard-dose levels. Such stem cell-support treatment strategies should not be offered outside the setting of a randomized clinical trial.
Taxanes (docetaxel and paclitaxel) have recently been demonstrated to be among the most active agents in the treatment of metastatic breast cancer. As a result, several studies have explored the clinical utility of adding these drugs to standard AC treatment programs in the adjuvant treatment of lymph node-positive, localized breast cancer. Although a number of such trials have completed accrual and others remain in progress, currently available data are inconclusive and do not permit definitive recommendations regarding the impact of taxanes on either relapse-free or overall survival. There is no evidence to support the use of taxanes in lymph node-negative breast cancer outside the setting of a clinical trial.
Available data demonstrate that chemotherapy and tamoxifen are additive in their impact on survival when employed as adjuvant treatment of breast cancer. Therefore, most patients with hormone receptor-positive tumors who are receiving chemotherapy should receive tamoxifen.
At the present time, there are no convincing data to support the use of any known biologic factor in selecting a specific adjuvant chemotherapy regimen in breast cancer. Future prospective studies are needed to determine if such factors in an individual patient (e.g., HER-2/neu overexpression) should influence the choice of adjuvant cytotoxic therapy.
Despite the favorable impact of adjuvant chemotherapy on long-term survival in patients with breast cancer, it is important to determine whether there are specific patient populations for whom it is reasonable to avoid the administration of cytotoxic chemotherapy. Unfortunately, very limited information is available to answer this important question. On the basis of available data, it is accepted practice to offer cytotoxic chemotherapy to most women with lymph node metastases or with primary breast cancers larger than 1 cm in diameter (both lymph node-negative and lymph node-positive). For women with lymph node-negative cancers smaller than 1 cm in diameter, the decision to consider chemotherapy should be individualized.
Similarly, in patients with small lymph node-negative breast cancers with favorable histologic subtypes, such as tubular and mucinous cancers, retrospective data support long-term survival following primary therapy without the need for adjuvant chemotherapy.
There are limited data to define the optimal use of adjuvant chemotherapy for women more than 70 years of age. It is likely that there is a survival benefit associated with the administration of chemotherapy in this population of patients. There is legitimate concern, however, regarding the toxicity associated with cytotoxic regimens in this population. In addition, existing comorbid medical conditions and mortality from noncancer causes will influence the overall benefits in this group of women. The decision to treat women over the age of 70 years with adjuvant chemotherapy will need to consider these factors. Increased participation of women over the age of 70 years in randomized clinical trials and studies specifically addressing the value and tolerance of adjuvant chemotherapy in these women are urgently needed.
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4) FOR WHICH PATIENTS SHOULD POSTMASTECTOMY RADIOTHERAPY BE RECOMMENDED? |
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Recent randomized controlled trials have demonstrated superior tumor control and overall survival rates with the addition of postmastectomy radiotherapy. A recent meta-analysis of more than 22 000 women in which adjuvant radiotherapy was compared with no radiotherapy reported an improvement in locoregional tumor control rates from 70% to 90%. This increase resulted in a statistically significant improvement in the overall survival rate and in the disease-specific survival rate in the study population after a follow-up time of 20 years. These findings lend support to the concept that improving locoregional tumor control rates in breast cancer can lead to an improvement in survival rates.
The potential benefits of postmastectomy radiotherapy must be weighed against both the acute and the long-term side effects of this therapy. The same meta-analysis documented an excess of non-breast cancer deaths, the majority of which were vascular in nature. These deaths were probably related to the high radiotherapy doses received by the heart and great vessels through the use of outdated radiotherapy techniques. Contemporary radiotherapy delivery employing image-based planning has substantially reduced the radiotherapy dose received by these structures. Although the duration of follow-up of women treated with modern radiotherapeutic techniques is more limited, preliminary data show no apparent increase in vascular deaths. Postmastectomy radiotherapy, however, is associated with an increased risk of arm edema.
There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy will benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary tumor. Postmastectomy radiotherapy must be coordinated with adjuvant multiagent chemotherapy and/or hormonal therapy. Radiotherapy should not be delivered concurrently with anthracycline chemotherapy and should be delivered within the first 6 months after mastectomy. In most circumstances, combined modality adjuvant therapy begins with several courses of chemotherapy. Radiotherapy, as part of such treatment programs, should be delivered with modern techniques designed to reduce the volume of heart and great vessels receiving radiotherapy. At this time, the role of postmastectomy radiotherapy for women with one to three positive lymph nodes remains uncertain and is being examined in a randomized clinical trial.
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5) HOW DO SIDE EFFECTS AND QUALITY-OF-LIFE ISSUES FACTOR INTO INDIVIDUAL DECISION-MAKING ABOUT ADJUVANT THERAPY? |
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Acute, Long-Term, and Late Medical Effects of Adjuvant Therapy
Adjuvant chemotherapy. Studies to date have documented a range of acute and late side effects of adjuvant chemotherapy that have the potential to substantially affect patients' quality of life. Most acute side effects (e.g., nausea and vomiting, mucositis, hair loss, and neutropenia) occur in varying degrees with the different chemotherapy regimens and resolve after treatment completion. The level of psychologic distress associated with chemotherapy also seems to vary between patients. Several randomized studies have found that the psychologic distress that patients experience is greater during more toxic adjuvant chemotherapy treatment, resolving soon after treatment completion. Similarly, 13 years after completing treatment, cancer survivors who had undergone any of the different adjuvant chemoendocrine therapies have distress levels equal to those of cancer survivors who had received no further adjuvant therapy.
The simultaneous combination of chemotherapy plus tamoxifen is associated with an increased risk of thromboembolism when compared with tamoxifen alone. Premature menopause, weight gain, and fatigue are the most frequent long- and short-term problems that have been documented. Several small studies have documented mild cognitive problems, such as those in memory, with precise levels of prevalence and severity yet to be determined. There is also a very small increase in the risk of treatment-related second malignancies and cardiac disease.
Adjuvant hormone therapy: tamoxifen and ovarian ablation. Hot flashes and vaginal discharge have been the most common side effects attributed to tamoxifen. Tamoxifen is associated with a small increased risk of endometrial cancer, pulmonary emboli, and deep vein thrombosis, particularly for women 50 years of age or older. The benefits of tamoxifen, however, far outweigh the risks. Tamoxifen has not been associated with an increase in depression, weight gain, nausea and vomiting, diarrhea, or problems in sexual functioning.
As with adjuvant chemotherapy, ovarian ablation is associated with the development of premature menopause and its associated symptoms including osteoporosis.
Decision-making in Adjuvant Therapy for Breast Cancer
Communication between patients and their physicians is the primary vehicle through which complex treatment decisions are made. This communication will likely be facilitated through the use of decision aids and well-designed patient information materials about the medical condition or procedure, treatment side effects, probabilities associated with health outcomes, and impact on quality of life. Findings from current research suggest that decision aids improve patients' knowledge about treatment options, reduce their anxiety about treatment decisions, enhance their comfort with treatment choices, and stimulate the patients to play a more active role in joint decision-making with their physicians.
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6) WHAT ARE PROMISING NEW RESEARCH DIRECTIONS FOR ADJUVANT THERAPY? |
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Randomized clinical trials should be conducted to better define the risks and benefits of continuing tamoxifen therapy beyond 5 years. Studies are also needed to expand experience with ovarian ablation, to explore the value of combined hormonal therapy, and to determine whether optimal hormonal therapy is equivalent, superior, or additive to chemotherapy in premenopausal women whose tumors express hormone receptor protein. The risks and benefits of new, selective estrogen receptor modulators and aromatase inhibitors should also be examined in the adjuvant setting.
Randomized clinical trials evaluating the roles of high-dose chemotherapy and taxanes need to be completed to determine whether these treatments have a role in the standard management of breast cancer. Additional studies are also needed to determine the importance of variations in the doses and schedules of the drugs used in chemotherapy regimens that are currently being accepted as standard. A particular emphasis should be placed on carefully designed studies to elucidate the clinical and biologic characteristics that may more accurately predict the effectiveness of specific adjuvant treatments in individual patients. As yet unproven treatments that must be critically evaluated in prospective trials in the adjuvant setting include trastuzumab, bisphosphonates, and newer chemotherapeutic and biologic agents.
To date, prospective trials of adjuvant therapy have failed to include sufficient numbers of women older than 70 years. Studies need to be designed that will determine the effectiveness of adjuvant therapies in this group of women.
The role of postmastectomy radiotherapy in women with one to three positive lymph nodes needs to be determined. Investigators should continue to explore the importance of risk factors for recurrence after mastectomy to improve the selection of patients who may benefit from adjuvant radiotherapy. To maximize the possible benefit of adjuvant radiotherapy, new radiation techniques should be developed that further reduce the radiation dose to normal tissues, such as the heart and lungs.
Although adjuvant therapy has been found to produce statistically significant improvements in survival, the ability to predict the value of these treatments in individual patients is limited. The development of accurate predictors of treatment efficacy would permit better targeting of treatments, improving efficacy and reducing the morbidity and cost of treatment. It is essential that the value of predictive and prognostic factors be evaluated with the use of standardized protocols in well-designed clinical studies with sufficient statistical power to detect clinically important differences. Successful integration of new technologies, such as tissue and expression microarrays and proteomics, will depend on careful design and analysis of clinical investigations. The value of sentinel lymph node biopsy and of sensitive assays for micrometastatic disease in lymph nodes and bone marrow should also be important priorities for clinical research.
Quality-of-life and late-effect evaluations should be integrated judiciously into selected clinical trials to better discern the acute and long-term influence of treatment on patients and their families. Interventions should be sought that will reduce side effects and improve quality of life. Decision aids and other techniques should be developed and evaluated for their ability to improve patients' involvement and understanding of treatment decisions.
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CONCLUSIONS |
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Generally accepted prognostic and predictive factors include age, tumor size, lymph node status, histologic tumor type, grade, mitotic rate, and hormone receptor status. Novel technologies, such as tissue and expression microarrays and proteomics, hold exciting potential. Progress, however, will depend on proper design and analysis of clinical and pathologic investigations.
Decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered to women whose tumors express hormone receptor protein. At present, 5 years of tamoxifen is standard adjuvant hormone therapy; ovarian ablation represents an alternative to adjuvant hormonal therapy for selected premenopausal women. Adjuvant hormonal therapy should not be recommended to women whose tumors do not express hormone receptor protein.
Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens.
Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment.
Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women.
There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial.
Individual patients differ in the importance that they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination.
CONSENSUS DEVELOPMENT PANEL
Patricia Eifel, M.D.
Panel and Conference Chairperson
Professor of Radiation Oncology
The University of Texas M. D. Anderson Cancer Center
Houston, TX
John A. Axelson, M.D., FACP
Hematology and Oncology Associates
Jackson, MI
Jose Costa, M.D.
Professor of Pathology and Biology
Director of Anatomic Pathology
Deputy Director, Yale Cancer Center
Vice Chairman, Department of Pathology
Yale University School of Medicine
New Haven, CT
John Crowley, Ph.D.
Biostatistician
Fred Hutchinson Cancer Research Center
Seattle, WA
Walter J. Curran, Jr., M.D.
Professor and Chairman
Department of Radiation Oncology
Thomas Jefferson University Hospital
Philadelphia, PA
Ann Deshler, R.N.
Administrative Director
Metro Minnesota Community Clinical Oncology Program
Institute for Research and Education of Health System Minnesota
St. Louis Park, MN
Shirley Fulton, J.D., M.B.A.
Superior Court Judge
Superior Court Judge Office
Charlotte, NC
Carolyn B. Hendricks, M.D.
Medical Oncologist
Suburban Specialty Care Physicians, P.C.
Bethesda, MD
Margaret Kemeny, M.D.
Surgeon
Chief of the Division of Surgical Oncology
University Hospital and Medical Center
State University of New York at Stony Brook
Stony Brook, NY
Alice B. Kornblith, Ph.D.
Director of Outcomes Studies
Department of Pain Medicine and Palliative Care and Cancer Center
Beth Israel Medical Center
New York, NY
Thomas A. Louis, Ph.D.
Senior Statistical Scientist
The RAND Corporation
Arlington, VA
Maurie Markman, M.D.
Director, The Cleveland Clinic
Taussig Cancer Center
Chairman, Department of Hematology and Medical Oncology
The Lee and Jerome Burkons Research Chair in Oncology
The Cleveland Clinic Foundation
Cleveland, OH
Robert Mayer, M.D.
Professor of Medicine
Harvard Medical School
Vice Chair for Academic Affairs
Department of Adult Oncology
Dana-Farber Cancer Institute
Boston, MA
Debra Roter, Dr.P.H.
Professor, Health Policy and Management
School of Hygiene and Public Health
The Johns Hopkins University
Baltimore, MD
SPEAKERS
Karen H. Antman, M.D.
Professor of Medicine
College of Physicians and Surgeons of Columbia University
Chief, Division of Medical Oncology
Director, Herbert Irving Comprehensive Cancer Center
New York, NY
Jonas C. Bergh, M.D., Ph.D.
Professor of Clinical and Molecular Oncology
Karolinska Institute and Hospital
Stockholm, Sweden
John L. Bryant, Ph.D.
Associate Professor of Biostatistics
University of Pittsburgh
Director, Biostatistical Center
National Surgical Adjuvant Breast and Bowel Project
Pittsburgh, PA
Gary M. Clark, Ph.D.
Professor of Medicine
Baylor Breast Center
Baylor College of Medicine
Houston, TX
Alan Coates, M.D., FRACP
International Breast Cancer Study Group
Chief Executive Officer
Australian Cancer Society
Sydney, New South Wales, Australia
Jack Cuzick, Ph.D.
Professor of Epidemiology
Head, Department of Mathematics, Statistics, and Epidemiology
Imperial Cancer Research Fund
London, U.K.
Maria Grazia Daidone, Ph.D.
Unit 10 Determinants of Prognosis and Treatment Response
Department of Experimental Oncology
Istituto Nazionale Tumori
Milan, Italy
Nancy E. Davidson, M.D.
Professor
The Johns Hopkins Oncology Center
The Johns Hopkins University School of Medicine
Baltimore, MD
Christina Davies, MBChB, M.Sc.
ATLAS Coordinator
Clinical Trial Service Unit
Radcliffe Infirmary
University of Oxford
Oxford, U.K.
James J. Dignam, Ph.D.
Statistician
National Surgical Adjuvant Breast and Bowel Project
Chicago, IL
Bernard Fisher, M.D.
Scientific Director
National Surgical Adjuvant Breast and Bowel Project
Distinguished Service Professor
University of Pittsburgh
Pittsburgh, PA
Patricia A. Ganz, M.D.
Professor, University of California, Los Angeles, Schools of Medicine and Public Health
Director, Division of Cancer Prevention and Control Research
Jonsson Comprehensive Cancer Center
Los Angeles, CA
Aron Goldhirsch, M.D.
Chairman, Scientific Committee, International Breast Cancer Study Group
Professor of Medical Oncology
Director, Division of Medical Oncology
European Institute of Oncology
Milan, Italy
Richard Gray, M.A., M.Sc.
Director
Clinical Trials Unit
University of Birmingham Medical School
Birmingham, U.K.
I. Craig Henderson, M.D.
Adjunct Professor of Medicine
University of California, San Francisco
San Francisco, CA
Gabriel N. Hortobagyi, M.D., FACP
Professor and Chairman
Department of Breast Medical Oncology
The University of Texas M. D. Anderson Cancer Center
Houston, TX
Amy S. Langer, M.B.A.
Executive Director
National Alliance of Breast Cancer Organizations
New York, NY
Mark Norman Levine, M.D.
Professor of Medicine
McMaster University
Hamilton, ON, Canada
Eleftherios P. Mamounas, M.D.
Medical Director
Cancer Center
Aultman Hospital
Canton, OH
Monica Morrow, M.D.
Professor of Surgery, Northwestern Memorial Hospital
Northwestern University Medical School
Director, Lynn Sage Comprehensive
Breast Program
Director of Cancer Department
American College of Surgeons
Chicago, II
Hyman B. Muss, M.D.
Associate Director, Vermont Cancer Center
Professor of Medicine, University of Vermont College of Medicine
Director of Hematology/Oncology
Fletcher Allen Health Care
University of Vermont
Burlington, VT
Larry Norton, M.D.
Head, Division of Solid Tumor Oncology
Norna S. Sarofim Chair in Clinical Oncology
Memorial Sloan-Kettering Cancer Center
New York, NY
C. Kent Osborne, M.D.
Professor
Baylor Breast Center
Baylor College of Medicine
Houston, TX
William P. Peters, M.D., Ph.D.
Director and Chief Executive Officer
Barbara Ann Karmanos Cancer Institute
Detroit, MI
Sir Richard Peto, F.R.S., M.Sc.
Early Breast Cancer Trialists'
Collaborative Group Secretariat
Professor of Medical Statistics and Epidemiology
Co-Director
Imperial Cancer Research Fund/Medical Research Council Clinical Trial Service Unit and Epidemiological Studies Unit
Radcliffe Infirmary, University of Oxford
Oxford, U.K.
Martine J. Piccart, M.D., Ph.D.
Chairman, Breast International Group
Head, Chemotherapy Department
Jules Bordet Institute
Brussels, Belgium
Lori Pierce, M.D.
Associate Professor
Department of Radiation Oncology
University of Michigan Medical Center
Ann Arbor, MI
Peter Ravdin, M.D., Ph.D.
Associate Professor
Department of Medicine
Division of Medical Oncology
University of Texas Health Science Center at San Antonio
San Antonio, TX
Stuart J. Schnitt, M.D.
Associate Professor of Pathology
Harvard Medical School
Director of Surgical Pathology
Beth Israel Deaconess Medical Center
Boston, MA
George W. Sledge, Jr., M.D.
Ballvé-Lantero Professor of Oncology
Department of Medicine
Indiana University School of Medicine
Indianapolis, IN
Eric P. Winer, M.D.
Associate Professor of Medicine
Department of Adult Oncology
Dana-Farber Cancer Institute
Boston, MA
Norman Wolmark, M.D.
Chairman, National Surgical Adjuvant Breast and Bowel Project
Chairman and Professor
Department of Human Oncology
Allegheny General Hospital
Pittsburgh, PA
William C. Wood, M.D., FACS
Joseph Brown Whitehead Professor and Chairman
Department of Surgery
Emory University School of Medicine
Atlanta, GA
PLANNING COMMITTEE
Jeffrey Abrams, M.D.
Planning Committee Chairperson
Senior Investigator
Clinical Investigation Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
National Institutes of Health
Bethesda, MD
Marietta Anthony, Ph.D.
Director, Women's Health Research
Department of Pharmacology
Georgetown University Medical Center
Washington, DC
Karen H. Antman, M.D.
Professor of Medicine
College of Physicians and Surgeons of Columbia University
Chief, Division of Medical Oncology
Director, Herbert Irving Comprehensive Cancer Center
New York, NY
Christine D. Berg, M.D.
Director, Suburban Hospital Cancer Center
Affiliated with The Johns Hopkins Oncology Center
Bethesda, MD
John A. Bowersox
Communications Specialist
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, MD
John L. Bryant, Ph.D.
Associate Professor of Biostatistics
University of Pittsburgh
Director, Biostatistical Center
National Surgical Adjuvant Breast and Bowel Project
Pittsburgh, PA
Alan Coates, M.D., FRACP
International Breast Cancer Study Group
Chief Executive Officer
Australian Cancer Society
Sydney, Australia
Nancy E. Davidson, M.D.
Professor
The Johns Hopkins Oncology Center
The Johns Hopkins University School of Medicine
Baltimore, MD
Patricia Eifel, M.D.
Professor of Radiation Oncology
The University of Texas M. D. Anderson Cancer Center
Houston, TX
Jerry M. Elliott
Program Analysis and Management Officer
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, MD
John H. Ferguson, M.D.
Consultant, Office of Rare Diseases
National Institutes of Health
Bethesda, MD
Patricia A. Ganz, M.D.
Professor, University of California, Los Angeles, Schools of Medicine and Public Health
Director, Division of Cancer Prevention and Control Research
Jonsson Comprehensive Cancer Center
Los Angeles, CA
Gabriel N. Hortobagyi, M.D., FACP
Professor and Chairman
Department of Breast Medical Oncology
The University of Texas M. D. Anderson Cancer Center
Houston, TX
Karen Eubanks Jackson
National President and Founder
Sisters Network, Inc.
Houston, TX
Barnett S. Kramer, M.D., M.P.H.
Director
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, MD
Amy S. Langer, M.B.A.
Executive Director
National Alliance of Breast Cancer Organizations
New York, NY
Daniel J. O'Neal III, R.N., M.A.
Chief
Office of Science Policy and Public Liaison
National Institute of Nursing Research
National Institutes of Health
Bethesda, MD
Lori Pierce, M.D.
Associate Professor
Department of Radiation Oncology
University of Michigan Medical Center
Ann Arbor, MI
Charles R. Sherman, Ph.D.
Deputy Director
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, MD
Sheila E. Taube, Ph.D.
Associate Director of Cancer Diagnosis Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
National Institutes of Health
Bethesda, MD
Ann Thor, M.D.
Professor
Departments of Pathology and Surgery
Northwestern University Medical School
Evanston Northwestern Healthcare
Evanston, IL
William C. Wood, M.D., FACS
Joseph Brown Whitehead Professor and Chairman
Department of Surgery
Emory University School of Medicine
Atlanta, GA
JoAnne Zujewski, M.D.
Senior Medical Oncologist
Division of Clinical Sciences
National Cancer Institute
National Institutes of Health
Bethesda, MD
CONFERENCE SPONSORS
National Cancer Institute
Richard D. Klausner, M.D.
Director
Office of Medical Applications of Research
Barnett S. Kramer, M.D., M.P.H.
Director
CONFERENCE CO-SPONSORS
National Institute of Nursing Research
Patricia A. Grady, Ph.D., R.N., FAAN
Director
Office of Research on Women's Health
Vivian W. Pinn, M.D.
Director
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NOTES |
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Editor's note: W. J. Curran, Jr., is conducting research sponsored by Bristol-Meyers Squibb Oncology, Wallingford, CT.
The following references were selected by the panel chair from references submitted with abstracts prepared by conference speakers.
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Manuscript received February 16, 2001; revised May 2, 2001; accepted May 10, 2001.
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