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114. Adjuvant Therapy for Breast Cancer
Consensus Development Conference Statement This statement was originally published as: Adjuvant Therapy for Breast Cancer. NIH Consens Statement 2000 November 1-3;17(4): 1-23.
For making bibliographic reference to consensus statement no. 114 in the electronic form displayed here, it isrecommended that the following format be used: Adjuvant Therapy for Breast Cancer. NIH Consens Statement Online 2000 November 1-3; [cited year, month, day]; 17(4): 1-23.
NIH Consensus Statements are prepared by a nonadvocate, non-Federal panel of experts, based on (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that are part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government.
1. Which factors should be used to select systemic adjuvant therapy? 2. For which patients should adjuvant hormonal therapy be recommended? 3. For which patients should adjuvant chemotherapy be recommended? Which agents should be used, and at what 4. For which patients should post-mastectomy radiotherapy be recommended? 5. How do side effects and quality-of-life issues factor into individual decision-making about adjuvant therapy? 6. What are promising new research directions for adjuvant therapy? cons/114/114_statement.htm - topcons/114/114_statement.htm - top Introduction
Each year, more than 180,000 women in the United States are diagnosed with breast cancer, the most common typeof noncutaneous cancer among women in this country. If current breast cancer rates remain constant, a woman borntoday has a one in ten chance of developing breast cancer.
Because of continuing research into new treatment methods, women with breast cancer now have more treatmentoptions and a better chance of long-term survival than ever before. The primary treatment of localized breast canceris either breast-conserving surgery and radiation or mastectomy with or without breast reconstruction. Systemicadjuvant therapies that are designed to eradicate microscopic deposits of cancer cells that may have spread ormetastasized from the primary breast cancer have been demonstrated to increase a woman's chance of long-termsurvival.
Systemic adjuvant therapies include chemotherapy (anticancer drugs) and hormone therapy. In addition to thesesystemic therapies, radiotherapy is used in selected cases as a local adjuvant treatment to destroy breast cancer cellsthat 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 treatmentdecisions can be made. The purpose of this conference was to establish a consensus regarding the use of adjuvanttherapy for breast cancer and to communicate that consensus to clinicians, patients, and the general public. Afterreading 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 waspresented to the conference audience on the third day. The consensus development panel's statement addresses thefollowing key questions: 1. Which factors should be used to select systemic adjuvant therapy?2. For which patients should adjuvant hormonal therapy be recommended?3. For which patients should adjuvant chemotherapy be recommended? Which agents should be used, and at 4. For which patients should post-mastectomy radiotherapy be recommended?5. How do side effects and quality-of-life issues factor into individual decision-making about adjuvant 6. What are promising new research directions for adjuvant therapy? This conference was sponsored by the National Cancer Institute and the NIH Office of Medical Applications ofResearch. The co-sponsors included the National Institute of Nursing Research and the NIH Office of Research onWomen's Health.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top 1. Which factors should be used to select systemic adjuvant therapy?
The selection of systemic adjuvant therapy is based on prognostic and predictive factors. Prognostic factors aremeasurements available at diagnosis or time of surgery that, in the absence of adjuvant therapy, are associated withrecurrence rate, death rate, or other clinical outcome. Predictive factors are measurements associated with degree ofresponse to a specific therapy. For example, a demonstration of hormone receptors in tumor cells predicts theresponse to hormonal therapy. Any factor has the potential to be both prognostic and predictive, and a factor'simportance depends on both the clinical endpoint and on the method of treatment comparison.
Prognostic and predictive factors fall into three categories: patient characteristics that are independent of the disease(such as age); disease characteristics (such as tumor size and histologic type); and biomarkers (measurableparameters in tissues, cells, or fluids), such as hormone receptor status, progesterone receptor status, and measuresof cell turnover. Accepted prognostic and predictive factors include age, tumor size, axillary node status, histologicaltumor type, standardized pathologic grade, and hormonal-receptor status.
The median age for the diagnosis of breast cancer is between the ages of 60 and 65 years. Some younger women(particularly under 35 years) have a more agressive form of the disease, characterized by larger tumors of highergrade with vascular invasion. Elderly women (over 70 years) with breast cancer frequently have hormone receptorprotein in their malignant tissue, suggesting a more indolent tumor pattern and a high likelihood of response tohormonal therapy.
Race appears to be a prognostic but not predictive factor. In contrast to white women, black breast cancer patientsare generally younger, often have larger tumors at diagnosis, and a smaller percentage have hormone receptors intheir tumor tissue. These factors contribute to a poorer prognosis. In cases of similar clinical presentation, however,adjuvant treatment confers similar benefits to black and white women. Research on the benefits and risks ofadjuvant therapy in Hispanic, Asian, and Native American women is needed.
Novel technologies (such as tissue and expression microarrays and proteomics) present exciting potential, but theirintegration into clinical practice will depend on the proper design and analysis of clinical investigations. The same istrue for overexpression of HER-2/neu, p53 status, histologic evidence of vascular invasion, and quantitativeparameters of angiogenesis. These have been extensively studied clinically and biologically, but do not have anestablished role in patient management. For example, although overexpression/amplification of HER-2/neu isassociated with an adverse outcome in node-positive patients and may predict the response to therapy, laboratorymethods 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 towhether 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 prospectiveclinical trials before they directly alter patient management.
It is essential that the value of predictive and prognostic factors be evaluated in well-designed clinical studies thatare based on standardized protocols and have sufficient statistical power. Because these standards are infrequentlymet, very few new prognostic or predictive factors have been validated in the last 10 years, and future progress willdepend 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 andprognostic/predictive value is studied. Since no single study will have sufficient power to properly evaluate predictive value, results from these trials should be combined.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top 2. For which patients should adjuvant hormonal therapy be
recommended?
The decision whether to recommend adjuvant hormonal therapy should be based on the presence of hormonereceptors, as assessed by immunohistochemical staining of breast cancer tissue. If the available tissue is insufficientto determine hormone receptor status, it should be considered as being positive, particularly in postmenopausalwomen. The small subset of women whose tumors lack hormone receptor protein but contain progesterone receptoralso appear to benefit from hormonal therapy. The presence or absence of HER?2/neu overexpression should notinfluence the decision to recommend hormonal therapy.
The goal of hormonal therapy is to prevent breast cancer cells from receiving stimulation from estrogen. Suchstimulation occurs primarily in tumors that contain hormone receptor protein. Estrogen deprivation can be achievedby (a) blocking the receptor through the use of drugs, such as tamoxifen; (b) suppression of estrogen synthesisthrough the administration of aromatase inhibitors (e.g., anastrozole) in postmenopausal women or LHRH agonists(e.g., goserelin) in premenopausal women; or (c) destruction of the ovaries through surgery or external beamradiation therapy. The administration of cytotoxic chemotherapy may indirectly accomplish this same effect bydamaging estrogen-producing cells in the ovaries.
Adjuvant hormonal therapy should be recommended to women whose breast tumors contain hormone receptorprotein, regardless of age, menopausal status, involvement of axillary lymph nodes, or tumor size. While thelikelihood of benefit correlates with the amount of hormone receptor protein in tumor cells, patients with any extentof hormone receptor in their tumor cells may still benefit from hormonal therapy. Such treatment has led tosubstantial reductions in the likelihood of tumor recurrence, second primary breast cancer, and death persisting for atleast 15 years of followup. Possible exceptions to this recommendation include premenopausal women with tumorsless than 10 mm in size who wish to avoid the symptoms of estrogen deprivation or elderly women with similarlysized 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 haveshown that 5 years of tamoxifen are superior to 1 to 2 years of such treatment. Currently, there are no convincingdata that justify the use of tamoxifen for longer than 5 years outside the setting of a clinical trial. Althoughtamoxifen has been associated with a slight but definite increased risk of endometrial cancer and venousthromboembolism, the benefit of tamoxifen treatment far outweighs its risks in the majority of women. Neithertransvaginal ultrasonography nor endometrial biopsies are indicated as screening maneuvers for endometrial cancerin asymptomatic women taking tamoxifen. Tamoxifen may be combined with combination chemotherapy,particularly in premenopausal women; such combinations may further reduce the risk of recurrence. There are nodata to support the use of raloxifene or aromatase inhibitors as adjuvant hormonal therapy at this time.
For hormone receptor positive premenopausal patients, alternative strategies of hormonal therapy, which are usedfar less frequently in the United States, include ovarian ablation through surgery, radiation therapy to the ovaries, orchemical suppression of ovarian function. Ovarian ablation appears to produce a similar benefit to somechemotherapy regimens. Combining ovarian ablation with chemotherapy has not been shown to provide an additional advantage to date. The value of combining hormonal therapies has not yet been adequately explored.
Hormonal adjuvant therapy should not be recommended to women whose breast cancers do not express hormonereceptor protein. Randomized clinical trials have not yet shown that such treatment substantially reduces thelikelihood of recurrence or, in the case of tamoxifen, diminishes the likelihood of contralateral breast cancer.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top 3. For which patients should adjuvant chemotherapy be
recommended? Which agents should be used, and at what dose or
schedule?
Over the past decade, data have emerged that more clearly define the subpopulations of women with localized breastcancer for whom adjuvant chemotherapy is indicated as a standard component of treatment. Chemotherapy has beenshown to substantially improve the long-term, relapse-free, and overall survival in both premenopausal andpostmenopausal women up to age 70 years with node-positive and node-negative disease.
Randomized clinical trials have attempted to define optimal chemotherapy regimens, doses, and schedules in theadjuvant treatment of breast cancer. These studies, along with the results of overview analyses, permit a number ofconclusions to be drawn.
The administration of polychemotherapy (> 2 agents) is superior to single agents. Four to six courses of treatment (3to 6 months) appear to provide optimal benefit, with the administration of additional courses adding to toxicitywithout substantially improving overall outcome. However, definitive data on the benefits of more prolongedtreatment are lacking and future research is needed to directly address this clinically relevant issue.
Anthracyclines (such as doxorubicin and epirubicin) have been used as components of adjuvant polychemotherapyfor breast cancer. Available data indicate that adjuvant chemotherapy regimens that include an anthracycline resultin a small but statistically significant improvement in survival compared to nonanthracycline-containing programs.
There is no evidence for excessive cardiac toxicity in women without significant preexisting heart disease treatedwith anthracyclines at the cumulative doses utilized in standard adjuvant programs. In clinical practice, the decisionto use an anthracycline in an individual patient should take into consideration the potential survival benefits versusspecific 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 appearto result in a comparable survival outcome, whether given preoperatively or postoperatively. However, AC has notbeen compared to 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 ofanthracycline-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 to the administrationof polychemotherapy programs at standard dose levels. Such stem cell-support treatment strategies should not beoffered outside the setting of a randomized clinical trial.
Taxanes (docetaxel, paclitaxel) have recently been demonstrated to be among the most active agents in the treatmentof metastatic breast cancer. As a result, several studies have explored the clinical utility of adding these drugs tostandard doxorubicin/cyclophosphamide treatment programs in the adjuvant treatment of node-positive, localizedbreast cancer. Although a number of such trials have completed accrual and others remain in progress, currentlyavailable data are inconclusive and do not permit definitive recommendations regarding the impact of taxanes oneither relapse-free or overall survival. There is no evidence to support the use of taxanes in node-negative breastcancer outside the setting of a clinical trial.
Available data demonstrate that chemotherapy and tamoxifen are additive in their impact on survival whenemployed as adjuvant treatment of breast cancer. Therefore, most patients with hormone receptor positive tumorswho are receiving chemotherapy should receive tamoxifen.
At the present time, there are no convincing data to support the use of any known biological factor in selecting aspecific adjuvant chemotherapy regimen in breast cancer. Future prospective studies are needed to determine if suchfactors in an individual patient (e.g., HER?2/neu overexpression) should influence the choice of adjuvant cytotoxictherapy.
Despite the favorable impact of adjuvant chemotherapy on long-term survival in breast cancer, it is important todetermine whether there are specific patient populations for whom it is reasonable to avoid the administration ofcytotoxic chemotherapy. Unfortunately, very limited information is available to answer this important question. Onthe basis of available data, it is accepted practice to offer cytotoxic chemotherapy to most women with primarybreast cancers larger than 1 cm in diameter (both node-negative and node-positive). For women with node-negativecancers less than 1 cm in diameter, the decision to consider chemotherapy should be individualized.
Similarly, in patients with small, node-negative breast cancers with favorable histologic subtypes, such as tubularand 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. Itis likely that there is a survival benefit associated with the administration of chemotherapy in this patient population.
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 overallbenefits in this group of women. The decision to treat women over the age of 70 with adjuvant chemotherapy willneed to consider these factors. Increased participation of women over 70 in randomized clinical trials and studiesspecifically addressing the value and tolerance of adjuvant chemotherapy in these women are urgently needed.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top 4. For which patients should post-mastectomy radiotherapy be
recommended?
The standard of care for breast conservation includes surgery followed by breast radiotherapy. Before the advent ofeffective adjuvant chemotherapy, post-mastectomy radiotherapy was commonly employed. Interest in this approachwas revived after several studies identified patient subgroups with 20 to 40 percent rates of locoregional recurrenceafter mastectomy and chemotherapy. These subgroups, which included women with four or more positive lymph nodes or an advanced primary tumor (a tumor of 5 cm or greater or a tumor invading the skin or adjacentmusculature), were thought most likely to benefit from a course of post-mastectomy radiotherapy.
Recent randomized controlled trials have demonstrated superior tumor control and overall survival rates with theaddition of post-mastectomy radiotherapy. A recent meta-analysis of more than 22,000 women comparing adjuvantradiotherapy to no radiotherapy reported an improvement in locoregional tumor control rates from 70 percent to 90percent. This resulted in a significant improvement in the overall survival rate and in the disease-specific survivalrate after a followup time of 20 years. These findings lend support to the concept that improving locoregional tumorcontrol rates in breast cancer can lead to an improvement in survival rates.
The potential benefits of post-mastectomy radiotherapy must be weighed against both the acute and long-term sideeffects of this therapy. The same meta-analysis documented an excess of non-breast cancer deaths, the majority ofwhich were vascular in nature. These deaths were probably related to the high radiotherapy doses received by theheart and great vessels through the use of outdated radiotherapy techniques. Contemporary radiotherapy deliveryemploying image-based planning has substantially reduced the radiotherapy dose received by these structures.
Although the duration of followup of women treated with modern techniques is more limited, the preliminary datashow no apparent increase in vascular deaths. Post-mastectomy radiotherapy, however, is associated with anincreased risk of arm edema.
There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy will benefit frompostoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or anadvanced primary tumor. Post-mastectomy radiotherapy must be coordinated with adjuvant multiagentchemotherapy and/or hormonal therapy. Radiotherapy should not be delivered concurrently with anthracyclinechemotherapy and should be delivered within the first 6 months following mastectomy. In most circumstances,combined modality adjuvant therapy begins with several courses of chemotherapy. Radiotherapy, as part of suchtreatment programs, should be delivered with modern techniques designed to reduce the volume of heart and greatvessels receiving radiotherapy. At this time, the role of post-mastectomy radiotherapy for women with one to threepositive lymph nodes remains uncertain and are being examined in a randomized clinical trial.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top 5. How do side effects and quality-of-life issues factor into individual
decision-making about adjuvant therapy?
Adjuvant therapy decisions are complicated by marginal differences in treatment results and risk-benefit profiles,
balancing acute effects with long-term outcomes. Individual patients differ in the value they place on these issues.
Retrospective studies report that women may be willing to undergo treatment for as little as a 1 to 2 percent
improvement in the probability of survival. Clear communication of benefits and risks is an essential component in
enabling as informed a joint treatment decision as possible. Absolute and relative risks of therapy must be discussed
openly.
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 for significantly affecting patients' quality of life. Most acute side effects (e.g., nausea and vomiting,
mucositis, hair loss, neutropenia) occur in varying degrees in the different chemotherapy regimens and resolve after
treatment completion. This also seems to be true for psychological distress. Several randomized studies have found
that the psychological distress patients experience is greater during more toxic adjuvant chemotherapy treatment,
resolving soon after treatment completion. Similarly, 1 to 3 years after completing treatment, the distress levels of
cancer survivors who had undergone any of the different adjuvant chemoendocrine therapies equal the levels of
those who had received no further adjuvant therapy.
The simultaneous combination of chemotherapy plus tamoxifen is associated with an increased risk of
thromboembolism when compared to 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, deep vein thrombosis, particularly
for those women 50 years old or older. The benefits, 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 treatmentdecisions 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, probabilitiesassociated with health outcomes, and impact on quality of life. Findings from current research suggest that decisionaids improve patients' knowledge about treatment options, reduce patients' anxiety about treatment decisions andenhance their comfort with treatment choices, and stimulate patients to play a more active role in joint decision-making with their physicians.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top 6. What are promising new research directions for adjuvant therapy?
During the past decade, major advances in adjuvant treatment of breast cancer have resulted from analyses of largeprospective randomized trials. In the United States, however, fewer than 3 percent of cancer patients are entered inclinical trials. To achieve continued improvements in adjuvant treatment, efforts should be made to improve patientand physician participation in these studies. A number of important questions remain to be answered.
Randomized clinical trials should be conducted to better define the risks and benefits of continuing tamoxifentherapy beyond 5 years. Studies are also needed to expand experience with ovarian ablation, to explore the value ofcombined hormonal therapy, and to determine whether optimal hormonal therapy is equivalent, superior, or additiveto chemotherapy in premenopausal women whose tumors express hormone receptor protein. The risks and benefitsof new, selective estrogen receptor modulators (SERMs) and aromatase inhibitors should also be examined in theadjuvant setting.
Randomized clinical trials evaluating the roles of high dose chemotherapy and taxanes need to be completed todetermine whether these treatments have a role in the standard management of breast cancer. Additional studies arealso needed to determine the importance of variations in the doses and schedules of the drugs used in chemotherapyregimens that are currently accepted as being standard. A particular emphasis should be placed on carefully designedstudies to determine the clinical and biological characteristics that may more accurately predict the effectiveness ofspecific adjuvant treatments in individual patients. As yet unproven treatments that must be critically evaluated inprospective trials in the adjuvant setting include trastuzumab, bisphosphonates, and newer chemotherapeutic andbiologic agents.
To date, prospective trials of adjuvant therapy have failed to include sufficient numbers of women older than 70years. Studies need to be designed that will determine the effectiveness of adjuvant therapies in this group ofwomen.
The role of post-mastectomy radiotherapy in women with 1 to 3 positive lymph nodes needs to be determined.
Investigators should continue to explore the importance of risk factors for recurrence after mastectomy to improvethe selection of patients who may benefit from adjuvant radiotherapy. To maximize the possible benefit of adjuvantradiotherapy, 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 significant improvements in survival, the ability to predict thevalue of these treatments in individual patients is limited. The development of accurate predictors of treatmentefficacy would permit better targeting of treatments, improving efficacy and reducing the morbidity and cost oftreatment. It is essential that the value of predictive and prognostic factors be evaluated using standardized protocolsin 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 dependon careful design and analysis of clinical investigations. The value of sentinel lymph node biopsy and of sensitiveassays 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 judiciously integrated into selected clinical trials to betterdiscern the acute and long-term influence of treatment on patients and their families. Interventions should be soughtthat will reduce side effects and improve quality of life. Decision aids and other techniques should be developed andevaluated for their ability to improve patients' involvement and understanding of treatment decisions.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top Conclusions
During the past 10 years, substantial progress has been made in the treatment of breast cancer. For the first time,breast cancer mortality rates are decreasing in the United States. Refinements of adjuvant treatment have contributedto this advance.
Generally accepted prognostic and predictive factors include age, tumor size, lymph node status, histological tumortype, grade, mitotic rate, and hormonal receptor status. Novel technologies, such as tissue and expression microarrays and proteomics, hold exciting potential. Progress, however, will depend on proper design and analysisof clinical and pathological investigations.
Decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein intumor tissues. Adjuvant hormonal therapy should be offered to women whose tumors express hormone receptorprotein. At present five years of tamoxifen is standard adjuvant hormone therapy; ovarian ablation represents analternative option for selected premenopausal women. Adjuvant hormonal therapy should not be recommended towomen whose tumors do not express hormone receptor protein.
Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women withlocalized breast cancer regardless of nodal, menopausal, or hormone receptor status. The inclusion of anthracyclinesin adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival overnonanthracycline-containing regimens.
Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of node-positive breastcancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes innode-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatmentstrategies should be supported to determine if they 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 roleof adjuvant chemotherapy in these women.
There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit frompostoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or anadvanced primary cancer. Currently, the role of post-mastectomy radiotherapy for patients with one to three positivelymph nodes remains uncertain and should be tested in a randomized controlled trial.
Individual patients differ in the importance 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, andfatigue. Methods to support shared decision-making between patients and their physicians have been successful intrials; they need to be tailored for diverse populations and should be tested for broader dissemination.
cons/114/114_statement.htm - topcons/114/114_statement.htm - top Consensus Development Panel
Patricia Eifel, M.D.
Panel and Conference Chairperson
Professor of Radiation Oncology
M.D. Anderson Cancer Center
University of Texas
Houston, Texas
John A. Axelson, M.D., FACP
Hematology and Oncology Associates
Jackson, Michigan
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, Connecticut
John Crowley, Ph.D.
Biostatistician
Fred Hutchinson Cancer Research Center
Seattle, Washington
Walter J. Curran, Jr., M.D.
Professor and Chairman
Department of Radiation Oncology
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania
Ann Deshler, R.N.
Administrative Director
Metro Minnesota CCOP
Institute for Research and Education of HealthSystem Minnesota
St. Louis Park, Minnesota
Shirley Fulton, J.D., M.B.A.
Superior Court Judge
Superior Court Judge Office
Charlotte, North Carolina
Carolyn B. Hendricks, M.D.
Medical Oncologist
Suburban Specialty Care Physicians, P.C.
Bethesda, Maryland
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, New York
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, New York
Thomas A. Louis, Ph.D.
Senior Statistical Scientist
The RAND Corporation
Arlington, Virginia
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, Ohio
Robert Mayer, M.D.
Professor of Medicine
Harvard Medical School
Vice Chair for Academic Affairs
Department of Adult Oncology
Dana-Farber Cancer Institute
Boston, Massachusetts
Debra Roter, Dr.P.H.
Professor, Health Policy and Management
School of Hygiene and Public Health
Johns Hopkins University
Baltimore, Maryland
cons/113/113_statement.htm - topcons/113/113_statement.htm - top
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, New York
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, Pennsylvania
Gary M. Clark, Ph.D.
Professor of Medicine
Baylor Breast Center
Baylor College of Medicine
Houston, Texas
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, United Kingdom
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
Johns Hopkins Oncology Center
Johns Hopkins University School of Medicine
Baltimore, Maryland
Christina Davies, MBChB, M.Sc.
ATLAS Coordinator
Clinical Trial Service Unit
Radcliffe Infirmary
University of Oxford
Oxford, United Kingdom
James J. Dignam, Ph.D.
Statistician
National Surgical Adjuvant Breast and Bowel Project
Chicago, Illinois
Bernard Fisher, M.D.
Scientific Director
National Surgical Adjuvant Breast and Bowel Project
Distinguished Service Professor
University of Pittsburgh
Pittsburgh, Pennsylvania
Patricia A. Ganz, M.D.
Professor, UCLA Schools of Medicine and Public Health
Director, Division of Cancer Prevention and Control Research
Jonsson Comprehensive Cancer Center
Los Angeles, California
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, United Kingdom
I. Craig Henderson, M.D.
Adjunct Professor of Medicine
University of California, San Francisco
San Francisco, California
Gabriel N. Hortobagyi, M.D., FACP
Professor and Chairman
Department of Breast Medical Oncology
M.D. Anderson Cancer Center
University of Texas
Houston, Texas
Amy S. Langer, M.B.A.
Executive Director
National Alliance of Breast Cancer Organizations (NABCO)
New York, New York
Mark Norman Levine, M.D.
Professor of Medicine
McMaster University
Hamilton, Ontario, Canada
Eleftherios P. Mamounas, M.D.
Medical Director
Cancer Center
Aultman Hospital
Canton, Ohio
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, Illinois
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, Vermont
Larry Norton, M.D.
Head, Division of Solid Tumor Oncology
Norna S. Sarofim Chair in Clinical Oncology
Memorial Sloan-Kettering Cancer Center
New York, New York
C. Kent Osborne, M.D.
Professor
Baylor Breast Center
Baylor College of Medicine
Houston, Texas
William P. Peters, M.D., Ph.D.
Director and Chief Executive Officer
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan
Sir Richard Peto, F.R.S., M.Sc.
Early Breast Cancer Trialists' Collaborative Group Secretariat
Professor of Medical Statistics and Epidemiology
Co-Director
ICRF/MRC Clinical Trial Service Unit and Epidemiological Studies Unit
Radcliffe Infirmary, University of Oxford
Oxford, United Kingdom
Martine J. Piccart, M.D., Ph.D.
Chairman, Breast International Group
Head, Chemotherapy Department
Jules Bordet Institute
B-1000 Brussels, Belgium
Lori Pierce, M.D.
Associate Professor
Department of Radiation Oncology
University of Michigan Medical Center
Ann Arbor, Michigan
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, Texas
Stuart J. Schnitt, M.D.
Associate Professor of Pathology
Harvard Medical School
Director of Surgical Pathology
Beth Israel Deaconess Medical Center
Boston, Massachusetts
George W. Sledge, Jr., M.D.
Ballv?-Lantero Professor of Oncology
Department of Medicine
Indiana University School of Medicine
Indianapolis, Indiana
Eric P. Winer, M.D.
Associate Professor of Medicine
Department of Adult Oncology
Dana-Farber Cancer Institute
Boston, Massachusetts
Norman Wolmark, M.D.
Chairman, National Surgical Adjuvant Breast and Bowel Project
Chairman and Professor
Department of Human Oncology
Allegheny General Hospital
Pittsburgh, Pennsylvania
William C. Wood, M.D., FACS
Joseph Brown Whitehead Professor and Chairman
Department of Surgery
Emory University School of Medicine
Atlanta, Georgia
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Planning Committee
Jeffrey Abrams, M.D.
Planning Committee Chairperson
Senior Investigator
Clinical Investigation Branch
Cancer Therapy Evaluation Program
National Cancer Institute
Bethesda, Maryland
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, New York
Christine D. Berg, M.D.
Director, Suburban Hospital Cancer Center
Affiliated with Johns Hopkins Oncology Center
Bethesda, Maryland
John A. Bowersox
Communications Specialist
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, Maryland
John L. Bryant, Ph.D.
Associate Professor of Biostatistics
University of Pittsburgh
Director, Biostatistical Center
National Surgical Adjuvant Breast and Bowel Project
Pittsburgh, Pennsylvania
Alan Coates, M.D., FRACP
International Breast Cancer Study Group
Chief Executive Officer
Australian Cancer Society
Sydney, Australia
Nancy E. Davidson, M.D.
Professor
Johns Hopkins Oncology Center
Johns Hopkins University School of Medicine
Baltimore, Maryland
Patricia Eifel, M.D.
Professor of Radiation Oncology
M.D. Anderson Cancer Center
University of Texas
Houston, Texas
Jerry M. Elliott
Program Analysis and Management Officer
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, Maryland
John H. Ferguson, M.D.
Potomac, Maryland
Patricia A. Ganz, M.D.
Professor, UCLA Schools of Medicine and Public Health
Director, Division of Cancer Prevention and Control Research
Jonsson Comprehensive Cancer Center
Los Angeles, California
Gabriel N. Hortobagyi, M.D., FACP
Professor and Chairman
Department of Breast Medical Oncology
M.D. Anderson Cancer Center
University of Texas
Houston, Texas
Karen Eubanks Jackson
National President and Founder
Sisters Network, Inc.
Houston, Texas
Barnett S. Kramer, M.D., M.P.H.
Director
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, Maryland
Amy S. Langer, M.B.A.
Executive Director
National Alliance of Breast Cancer Organizations (NABCO)
New York, New York
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, Maryland
Lori Pierce, M.D.
Associate Professor
Department of Radiation Oncology
University of Michigan Medical Center
Ann Arbor, Michigan
Charles R. Sherman, Ph.D.
Deputy Director
Office of Medical Applications of Research
Office of the Director
National Institutes of Health
Bethesda, Maryland
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, Maryland
Ann Thor, M.D.
Professor
Departments of Pathology and Surgery
Northwestern University Medical School
Evanston Northwestern Healthcare
Evanston, Illinois
William C. Wood, M.D., FACS
Joseph Brown Whitehead Professor and Chairman
Department of Surgery
Emory University School of Medicine
Atlanta, Georgia
JoAnne Zujewski, M.D.
Senior Medical Oncologist
Division of Clinical Sciences
National Cancer Institute
National Institutes of Health
Bethesda, Maryland
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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
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Conference Cosponsors
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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Source: http://www.chironc.it/biblioteca/nihconsstat.pdf