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Ann Oncol. Sep 2013; 24(9): 2206–2223.
Published online Aug 4, 2013. doi:  10.1093/annonc/mdt303
PMCID: PMC3755334

Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013

Abstract

The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and ‘triple-negative’ disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints.

Keywords: surgery, radiation therapy, systemic adjuvant therapies, early breast cancer, St Gallen Consensus, subtypes

introduction

The 2 years since the 2011 St Gallen Consensus [1] have seen substantial progress in evidence relevant to various aspects of the treatment of early invasive breast cancer. The genomic atlas of the disease [2] has emphasized its heterogeneity, and suggested that genomic studies may potentially inform treatment decisions such as the use of aromatase inhibitors [3, 4]. Further data became available reducing the necessity for axillary dissection [5, 6]. Studies presented at the 2012 ESMO meeting clarified the optimal duration of adjuvant trastuzumab in HER2-positive disease [7, 8]. The duration of adjuvant tamoxifen was addressed by the ATLAS study, which suggested a significant benefit for extending such treatment to 10 years rather than 5 years [9].

St Gallen 2013: news and progress

The 13th International Breast Cancer Conference held in St Gallen in March 2013 involved some 3700 participants from 95 countries and heard presentations from a faculty widely representative of disciplines and geographical areas. An Expert Panel, which included 51 members from 21 countries, chaired by Aron Goldhirsch and Eric P. Winer met at the conclusion of the conference to review the new information presented and consider treatment recommendations for broad application over the next 2 years. As in the past, this conference included an explicit approach to management of conflicts of interest (see Appendix 2).

Table Table11 summarizes the information presented during the conference.

Table 1.
Recent research findings presented at the 13th International Conference on Primary Therapy of Early Breast Cancer and their implications for patient care

Recent research in local therapy supports the continued trend towards less extensive procedures. Thus, axillary dissection can safely be omitted for patients with micrometastatic disease in sentinel nodes [65] and for those undergoing breast-conserving surgery and whole breast radiation therapy with up to two macroscopically positive sentinel nodes [66] (Table (Table11).

Two large studies [68, 69] support the safety and efficacy of shorter courses of whole breast radiation therapy (40 Gy in 15 or 42.5 Gy in 16 fractions), which offer advantages of convenience and cost over the previous standard of 50 Gy in 25 fractions.

New information became available for several aspects of systemic adjuvant therapy. The ATLAS trial reported superiority for 10 years compared with 5 years of adjuvant tamoxifen [9]. Further follow-up of the extended adjuvant study (MA.17) suggested particular benefit of letrozole for patients who were premenopausal at diagnosis but became postmenopausal by the time of letrozole administration [86].

The optimal duration of trastuzumab therapy in HER2-positive disease was clarified by results from two trials. The HERA trial [7] showed no additional benefit of 2 years trastuzumab compared with 1 year, while the PHARE trial [8] failed to show non-inferiority of 6 months trastuzumab compared with 1 year. Thus, the de facto standard of care remains 1 year of trastuzumab in patients with HER2-positive disease.

The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis of trials of chemotherapy versus no chemotherapy [18] failed to define any group for which chemotherapy did not offer an advantage. This conclusion is at odds with the results of individual trials and prospective/retrospective analyses of trials with assays such as the 21-gene recurrence score (RS). Furthermore, the control groups of trials included in the EBCTCG overview appear to exhibit much higher degrees of risk than that of patients with luminal disease seen in today's practice who receive modern endocrine therapy as the backbone for their treatment. The EBCTCG report noted that ‘information was lacking about tumour gene-expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both’ [18]. Subsequent editorial comments [93, 94] drew differing interpretations of the EBCTCG conclusions.

breast cancer subtypes

The clinico-pathological surrogate definitions of subtypes as adopted by the Panel are summarized in Table Table2,2, and their broad implications for systemic treatment selection are described in Table Table33.

Table 2.
Surrogate definitions of intrinsic subtypes of breast cancer
Table 3.
Systemic treatment recommendations

Further evidence has accrued in the last 2 years to support the use of multi-gene signatures to make distinctions among patients with luminal disease. Many different multi-gene assays provide prognostic information, primarily derived from their sampling of proliferation genes [97], which emphasizes the need for some measure of proliferation in any surrogate classification.

The 21-gene RS is accepted as providing not only prognostic, but also predictive information regarding the utility of cytotoxic therapy in addition to endocrine therapy for patients with luminal disease. This and perhaps other multi-gene assays can help define a group of patients for whom chemotherapy is futile because the biological nature of the tumour is such that it is substantially unresponsive to such agents. Existing studies of the 21-gene RS involve retrospective analysis of previously conducted randomized clinical trials [75, 76], which included both HER2-positive and HER2-negative cohorts. A recent report demonstrated excellent 5-year outcome without chemotherapy for a ‘good prognosis’ 70-gene signature cohort [49].

In those areas of the world where multi-gene assays are readily available, clinical practice has developed to rely on the results to guide decisions about inclusion of chemotherapy in the treatment of patients with ER-positive, HER2-negative disease. The 70-gene assay returns a dichotomous result, while 21-gene RS is continuous. An unresolved question is the level of RS which should justify cytotoxic therapy: only high RS values (>31) were significantly associated with chemotherapy benefit in the prospective/retrospective studies [75, 76], while substantially lower values are being investigated in ongoing prospective trials and are being used in clinical practice. For many societies, the cost of these multi-gene assays remains prohibitive.

The possibility that multi-gene expression assays may become more widely available was discussed by some Panellists after the meeting during the preparation of this manuscript. Cost-effectiveness studies have been carried out in the United States [98, 99], Canada [100104], Israel [105], the UK [106] and Germany [107, 108]. These studies have yielded varying estimates ranging from cost-saving to an incremental cost-effectiveness ratio (ICER) of ~US $60 000 per quality-adjusted life year (QALY). One Japanese study of the 70-gene assay [109] found an ICER of US $40 000 per QALY. Such assessments will be sensitive not only to the cost of the test, but to the net proportion of patients in whom testing leads to the omission of cytotoxic therapy, and to the cost of the cytotoxic regimen which would otherwise have been given. These reports have largely worked from the perspective of the health care system or third-party payer, and thus offer hope that such bodies may increasingly support multi-gene testing. It has recently been reported that the UK National Institute for Clinical Excellence, having reached a confidential pricing arrangement with the supplier, has issued a draft recommendation that the 21-gene RS be used for women with node-negative disease for whom the indication for chemotherapy is otherwise uncertain1. Meanwhile, in many settings patients can only access multi-gene testing by large personal out-of pocket payments, and therefore, from a global perspective for the immediate future multi-gene testing remains inaccessible for the majority of women with early breast cancer. It is for these women that the Panel believed that the approach adopted by successive St Gallen Panels based on the available clinico-pathological testing, and now expressed in the surrogate IHC-based classification shown in Table Table22 will be more widely applicable at lesser cost, notwithstanding its limited validation.

The main reason for attempting distinction between ‘Luminal A-like’ (more endocrine sensitive, indolent, better prognosis) and ‘Luminal B-like’ (less endocrine sensitive, more aggressive, worse prognosis) tumours was recognized to be the differing implications for the utility or futility of adjuvant cytotoxic therapy between these groups. Evidence was presented that the clarity of distinction between ‘Luminal A-like’ and ‘LuminalB-like’ tumours could be improved by the requirement for substantial PgR positivity in the definition of ‘Luminal A-like’ disease [24]. Adding this restriction will have the effect of reducing the number of patients classified as ‘Luminal A-like’ and thus increasing the number for whom cytotoxic therapy is generally recommended. Recognizing that high-quality pathology and quality assurance programmes are important for the interpretation of these tests, it was noted that the absolute values of each IHC parameter/cut-point may vary between laboratories, and that pending improved standardization local experience might best define the locally useful cut-points between ‘high’ and ‘low’ Ki-67 and PgR.

panel deliberations

The Panel reviewed a series of questions developed by iterative consultation over the months preceding the conference. Voting on most questions was in the format yes, no or abstain, where abstaining was recommended if the Panel member felt a conflict of interest in the question, that there was insufficient evidence to support an opinion either way or that he or she lacked the relevant expertise. Detailed voting records for each of the questions put to the Panel are provided in the supplementary Appendix S1, available at Annals of Oncology online.

surgery of the primary

The Panel found very few absolute contraindications to breast-conserving therapy. Margins involved with invasive carcinoma or DCIS after repeated resection were one such absolute contraindication. The minimal acceptable surgical margin was felt to be ‘no ink on invasive tumour’ (i.e. margins free of tumour) by nearly three quarters of the Panellists and most of the others would accept a minimum clearance of 1 mm. The Panel was almost unanimous that breast-conserving surgery should not be carried out unless postoperative radiation (if indicated, as described below in the radiation therapy section) could be delivered.

A majority of the Panel considered that relative but not absolute contraindications to breast-conserving therapy included very young age (<35 years); extensive or diffuse microcalcifications where the presence of malignancy cannot be reliably excluded without complete excision; multicentric disease; tumour location near the nipple and mutations of the BRCA1 or BRCA2 genes. Substantial minority support added multifocal disease, extensive vascular invasion and an extensive intraductal component to this list of relative contraindications. Positive family history and unfavourable biology based on genomic profiling were not considered to be contraindications to breast-conserving therapy.

Nipple-sparing surgery was considered acceptable, provided the margin close to the nipple was not involved. The vast majority of Panel members thought magnetic resonance imaging should not be routinely used in the assessment of newly diagnosed breast cancer.

surgery of the axilla

The Panel believed that axillary dissection could be safely omitted in patients with one or two positive sentinel nodes following breast-conserving surgery when whole breast radiation therapy is planned. The Panel was nearly equally divided whether this recommendation also applied to mastectomy followed by radiotherapy, but was almost unanimous in the need for axillary dissection if no radiotherapy was planned.

The Panel also considered that axillary dissection was required with three or more involved sentinel nodes or if nodes were clinically involved before surgery and confirmed by biopsy.

radiation therapy

The Panel strongly agreed that ‘short course’ radiotherapy, such as 40 Gy in 15 or 42.5 Gy in 16 fractions, could be offered as a standard for at least some patients, with a slim majority thinking that this would be suitable for almost all patients. The Panel agreed that short course radiotherapy was an option whether or not a boost to the tumour bed was planned. A large majority of Panel members thought that there were definable groups of patients not requiring radiotherapy following breast-conserving surgery, and that these might include the elderly and those with substantial comorbidity. The Panel could not reach a majority view regarding the current acceptability of the various techniques for partial breast radiation as definitive treatment.

Post-mastectomy radiotherapy was considered indicated by almost all Panel members for patients with four or more positive nodes, while the majority would not advise post-mastectomy irradiation for those with one to three positive nodes, except in the presence of adverse tumour pathology. The Panel was content to omit post-mastectomy radiotherapy with pathologic uninvolved nodes even when fewer than eight nodes had been examined and if the tumour was ≤5 cm. Two-thirds felt that radiation therapy should be given after mastectomy if positive sentinel nodes were not followed by axillary dissection.

Other indications recommended by the Panel for post-mastectomy radiotherapy included positive deep margins and, for two-thirds of the Panel, tumours greater than 5 cm regardless of the nodal status. However, the Panel strongly rejected needing radiotherapy solely based on Grade 3, lymphovascular invasion, HER2-positive status or triple-negative disease.

Areas to be irradiated following mastectomy and axillary dissection should not be influenced by any neoadjuvant systemic therapy or by the intrinsic subtype of the tumour. There was no clear agreement about the necessity to include the supraclavicular fossa, though trials have routinely included this area. Most Panel members would not include the internal mammary nodes and a strong majority felt that the axilla should not be radiated after dissection.

pathology

The Panel recognized substantial progress in the pathological characterization of tumour subtypes. There was little change in the classification of HER2-positive or triple-negative disease. The majority of the Panel accepted that a useful surrogate definition of Luminal A-like as distinct from Luminal B-like disease could be made using a combination of ER, PgR and Ki-67, without requiring molecular diagnostics. Ki-67 has been used for more than two decades as a prognostic marker in early breast cancer [110118]. The Panel did not accept that distinction between Luminal A-like and Luminal B-like tumours could be made with ER and PgR alone, and a clear majority voted that grade 3 could not be used as a substitute for high Ki-67 for this purpose. The Panel noted that standardized cut-offs for Ki-67 have not been established and laboratory specific values should be used, but the majority of the Panel voted that a threshold of ≥20% was clearly indicative of ‘high’ Ki-67 status. A minority questioned the role of Ki-67 in breast cancer treatment decisions. The Panel stressed the need for standardization, and that laboratories should participate in quality assurance programmes.

The Panel was strongly of the opinion that intrinsic subtypes, including those defined by the clinico-pathological surrogates, should influence whether or not chemotherapy was used, but not the choice of the cytotoxic regimen. After clinico-pathological assessment, a slim majority of the Panel was in favour of requesting a multi-gene assay in node-negative, ER-positive and HER2-negative cases. The Panel considered that only the 21-gene RS was predictive of chemotherapy responsiveness, though a substantial minority would also endorse PAM50 or the 70-gene signature for this purpose. This led to a recommendation that selection of patients who might forego chemotherapy could be based on the 21-gene RS, but the Panel did not offer majority endorsement for PAM50, the 70-gene signature or EPClin as yet established for this purpose.

For patients with ER-positive, HER2-negative disease, the use of molecular diagnostics was felt to be unnecessary in low-risk patients such as those with a tumour size of ≤1 cm in the setting of negative lymph nodes, since chemotherapy would be unlikely to be given anyway. Similarly, patients with a higher risk such as those with a tumour size >5 cm, inflammatory breast cancer, those with four or more involved nodes, or a very low ER positivity (e.g. 5%) might not benefit from molecular diagnostics because chemotherapy would be likely to be offered in any case. Patients in whom chemotherapy was thought to be of uncertain indication and who might, therefore, benefit from molecular diagnostics were felt to include selected patients with node-negative disease, those with one to three positive nodes, and patients aged <35.

In the determination of HER2 status for treatment purposes, the Panel did not believe that polysomy of chromosome 17, or heterogeneity of expression of HER2 need to be considered.

adjuvant endocrine therapy in premenopausal women

The large majority of the Panel said that tamoxifen alone was the default adjuvant endocrine therapy for premenopausal patients. In light of recent trial evidence, it was felt that at least some patients should have a treatment duration of 10 years, although this may not be needed by all patients. Most Panellists thought ovarian suppression need not be added to tamoxifen, but Panellists were evenly divided for patients <40 years of age. Most of the Panel regarded both ovarian suppression alone without tamoxifen and its combination with aromatase inhibitors as inappropriate unless tamoxifen was contraindicated.

adjuvant endocrine therapy in postmenopausal women

The Panel strongly believed that some postmenopausal women could be treated with tamoxifen alone. If an aromatase inhibitor were included in the regimen, Panellists were equally divided whether treatment should start with the aromatase inhibitor, although this strategy was strongly preferred for patients at high risk. Most Panellists believed that initial aromatase inhibitor therapy could be replaced by tamoxifen after 2 years, if there were a reason to do so. Extension of aromatase inhibitor therapy beyond the first five years for patients with node-positive, but not node-negative disease was strongly supported, for patients whose initial treatment was tamoxifen or whose initial therapy was <5 years of an aromatase inhibitor. The Panel was equally divided concerning an extended duration of aromatase inhibitor therapy beyond 5 years of treatment with these agents. Extended adjuvant endocrine therapy using tamoxifen is a consideration after a 5-year course of an aromatase inhibitor, though this approach has not been directly studied.

adjuvant cytotoxic chemotherapy

The Panel was clearly of the opinion that factors arguing for the inclusion of chemotherapy were histological grade 3 tumours, high Ki-67, low hormone receptor status, HER2 positivity or triple-negative status, high 21-gene RS, high-risk 70-gene signature and the involvement of more than three lymph nodes. Most felt that nodal positivity per se was not an indication for chemotherapy but very few would forego chemotherapy for patients with four or more positive nodes. Lymphovascular invasion was not recognized as an indication, while the Panel was equally divided whether young age (<35 years) was an indication.

The Panel was of the strong opinion that patients with Luminal A-like disease were ‘less responsive to chemotherapy’, but this treatment could be added to endocrine therapy based on the large tumour volume, assessment of risk or patient preference. The Panel did not select a specific chemotherapy regimen for these patients and expressed the view that any of the standard regimens, including the first- and second-generation regimens (CMF, AC, TC), could be considered.

For patients with Luminal B (HER2-negative) disease, the majority of the Panel considered chemotherapy to be indicated. Chemotherapy regimens for Luminal B (HER2-negative) disease should generally contain anthracyclines and (by a slim majority) taxanes. Half the Panel agreed that such chemotherapy should be delivered for at least six cycles, but the Panel did not endorse the exclusive use of a dose dense regimen.

For patients with HER2-positive disease, the Panel strongly believed, while there was no specifically preferred regimen, chemotherapy should include a taxane and, for most Panel members, also an anthracycline.

For patients with ‘basal-like’ (triple-negative ductal) disease, the Panel strongly endorsed both anthracyclines and taxanes, and did not believe that platinum, or regimens emphasizing alkylating agents were specifically required. There was no clear consensus on the role of dose dense regimens, though a substantial minority expressed support for such treatment.

General considerations influencing the choice of chemotherapy regimen were thought to include a desire to preserve fertility, the avoidance of alopecia and the presence of co-morbidities, but not intrinsic subtype or the presence of BRCA1 or BRCA2 mutation. Older chronological age should not necessarily influence the choice of regimen [119], but assessment of co-morbidities and general health was considered, especially important in older patients.

anti-HER2 therapies

For patients whose tumours show amplification or overexpression of HER2, the Panel considered that trastuzumab therapy was indicated for patients with tumours >5 mm, while some Panellists would treat patients with such tumours of any size. Most felt that trastuzumab should be given concurrently with a taxane, but not with an anthracycline. The Panel was prepared to endorse trastuzumab (with endocrine therapy, if indicated) without chemotherapy only if chemotherapy were contraindicated. The Panel was unanimous that the duration of trastuzumab should be 1 year.

neoadjuvant cytotoxic chemotherapy

The Panel was split about whether neoadjuvant chemotherapy had benefits beyond local downstaging. The Panel did not support additional postoperative adjuvant chemotherapy following a full course of neoadjuvant chemotherapy, whether or not pCR were achieved. Most believe when neoadjuvant therapy is given outside of a clinical trial, the full course of chemotherapy should be completed before surgery. In the unusual situation in which a surgery is carried out after less than a full course of neoadjuvant chemotherapy most Panel members would complete the course postoperatively.

neoadjuvant anti-HER2 therapy

For patients with HER2-positive disease, the Panel was strongly of the opinion that neoadjuvant treatment should include anti-HER2 drugs, and the majority recommended the use of chemotherapy plus trastuzumab alone (without additional anti-HER agents).

neoadjuvant endocrine therapy

The Panel strongly endorsed endocrine therapy alone as neoadjuvant treatment for postmenopausal patients with strongly positive hormone receptors and low proliferating disease, and most thought that such treatment should be continued until maximal response.

bisphosphonates

The Panel considered several situations in which bisphosphonates might be used with the aim of improving disease-free survival, but did not endorse such treatment for this purpose in any group, though a substantial minority felt that premenopausal patients receiving an LHRH agonist plus tamoxifen or clearly postmenopausal patients might derive benefit from such treatment. Denosumab was not endorsed for adjuvant use.

follow-up

The majority of the Panel believed that regular follow-up after the completion of immediate treatment (excluding long-term endocrine therapy) was appropriate, but that this could be supervised by a nurse specialist, rather than a surgeon or oncologist. The majority of the Panel also believed that follow-up should be done in person and not by telephone.

summary of treatment recommendations

The conference endorsed recent trial evidence supporting less extensive local therapies. It refined and re-iterated the value of clinico-pathological surrogate definitions resembling intrinsic subtypes to guide selection of systemic adjuvant therapies. The Panel recognized the superior accuracy and reproducibility of multi-gene molecular assays, but recognized that these assays are not available in all parts of the world. The Panel also noted the variability in the current levels of evidence to support the use of the individual multi-gene assays. Ongoing trials will prospectively define the value of chemotherapy in addition to endocrine therapy in patients with luminal disease in the node-negative (TAILORx, MINDACT) and node-positive (MINDACT, RxPONDER) cohorts. It is therefore to be hoped that a future St Gallen Consensus conference will be able to provide more robustly supported recommendations for treatment of such patients.

funding

Support for the conference was provided by SONK from registration fees paid by the conference attendees and by Grant No. CA75362 from the United States National Cancer Institute (IBCSG Statistical Center, R. Gelber, PI).

disclosure

The full COI statements of all authors are included in appendix 2.

Supplementary Material

Supplementary Data:

acknowledgements

We gratefully acknowledge the participants in the 13th St Gallen conference for their many useful suggestions. In addition to Panel members, we thank Drs. John Yarnold and Timothy J. Whelan for guidance in the development of the questions considered by the Panel. We thank Mrs. Sabina Briner, Dr. Carmen Criscitiello, and Mrs. Shari Gelber for their substantial assistance in the preparation of this report.

appendix 1

Members of the Panel are listed below. All had a significant input to the discussion and manuscript.

  • Kathy S. Albain, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, USA
  • Fabrice André, Research Director, Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
  • Jonas Bergh, Radiumhemmet & Karolinska Oncology, Karolinska Institutet and University Hospital, Stockholm, Sweden
  • Hervé Bonnefoi, Institut Bergonié Cancer Center, Université de Bordeaux, Bordeaux, France
  • Denisse Bretel-Morales, GECOPERU, Lima, Peru
  • Harold Burstein, Department of Medical Oncology/Solid Tumour Oncology, Dana-Farber Cancer Institute, Boston, USA
  • Fatima Cardoso, Breast Unit, Champalimaud Cancer Center, Lisbon, Portugal
  • Monica Castiglione-Gertsch, Oncogynaecology Unit, University Hospital, Geneva, Switzerland
  • Alan S. Coates, International Breast Cancer Study Group and University of Sydney, Sydney, Australia
  • Marco Colleoni, Research Unit Medical Senology, European Institute of Oncology, Milan, Italy
  • Alberto Costa, ESO—European School of Oncology, Milan, Italy and Breast Unit of Southern Switzerland, Lugano, Switzerland
  • Giuseppe Curigliano, Division of Medical Oncology, European Insitute of Oncology, Milan, Italy
  • Nancy E. Davidson, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute and UPMC Cancer Center, Pittsburgh, USA
  • Angelo Di Leo, ‘Sandro Pitigliani’ Medical Oncology Unit, Department of Oncology, Hospital of Prato, Prato, Italy
  • Bent Ejlertsen, Department of Oncology, Bldg 4262 Rigshospitalet, Copenhagen, Denmark
  • John F. Forbes, Department of Surgical Oncology, University of Newcastle, Calvary Mater Hospital, ANZ BCTG, Newcastle NSW, Australia
  • Richard D. Gelber, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA
  • Michael Gnant, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Wien, Austria
  • Aron Goldhirsch, Division of Medical Oncology, European Institute of Oncology, International Breast Cancer Study Group, Milan, Italy, and Ospedale Italiano, Viganello-Lugano, Switzerland (Chairman)
  • Pamela Goodwin, Department of Medicine, Division of Clinical Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital and Princess Margaret Hospital, University of TorontoToronto, Canada
  • Paul E. Goss, Department of Medicine, MGH Cancer Center, Boston, USA
  • Jay R. Harris, Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, USA
  • Daniel F. Hayes, Department of Internal Medicine, Breast Care Center, University of Michigan, Comprehensive Cancer Center, Ann Arbor, USA
  • Clifford A. Hudis, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, Memorial Hospital, and Weill Cornell Medical College, New York
  • James N. Ingle, Mayo Clinic Cancer Center, Women's Cancer Programme, Rochester, USA
  • Jacek Jassem, Deptartment of Oncology & Radiotherapy, Medical University of Gdansk, Gdansk, Poland
  • Zefei Jiang, 307 Hospital, Academy of Military Medical Sciences, Beijing, China
  • Per Karlsson, Department of Oncology, Institute of Selected Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Göteborg, Sweden
  • Sibylle Loibl, Unit Head of Medicine & Research, German Breast Group, GBG Forschungs GmbH, Neu-Isenburg, Germany
  • Monica Morrow, Memorial Sloan-Kettering Cancer Center, Evelyn Lauder Breast Center, New York, USA
  • Moise Namer, Medical Oncology, Center Antoine Lacassagne, Nice Cedex 2, France
  • C. Kent Osborne, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA
  • Ann H. Partridge, Department of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, USA
  • Frédérique Penault-Llorca, Service d'Anatomie Pathologie Moléculaire, Dépt. RIO, Center Jean Perrin, Clermont-Ferrand Cedex 1, France
  • Charles M. Perou, Departments of Genetics and Pathology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel HillChapel Hill, USA
  • Martine J. Piccart-Gebhart, Internal Medicine, Oncology, Institut Jules Bordet, Brussels, Belgium
  • Kathleen I. Pritchard, University of Toronto, Sunnybrook Odette Cancer Center, Ontario Clinical Oncology Group (OCOG), Toronto, Canada
  • Emiel J.T. Rutgers, Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Felix Sedlmayer, Department of Radiotherapy and Radiation Oncology, LKH Salzburg, Paracelsus Medical University Hospital, Salzburg, Austria
  • Vladimir Semiglazov, N.N. Petrov Research Institute of Oncology, St Petersburg, Russia
  • Zhi-Ming Shao, Fudan University, Cancer Hospital, Shanghai, China
  • Ian Smith, Breast Unit, Royal Marsden Hospital and Institute of Cancer Research, London, UK
  • Beat Thürlimann, Breast Center, Kantonsspital St Gallen, St Gallen, Switzerland
  • Masakazu Toi, Department of Breast Surgery, Kyoto University Hospital, Kyoto Japan
  • Andrew Tutt, Breast Oncology Unit, King's Health Partners AHSC, Guy's Hospital, London UK
  • Michael Untch, Department of Gynaecology and Obstetrics, Multidisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Academic Hospital of the University of Göttingen, Berlin, Germany
  • Giuseppe Viale, Department of Pathology, European Institute of Oncology and University of Milan, Milan, Italy
  • Toru Watanabe, Department of Medicine, Hamamatsu Oncology Center, Hamamatsu Japan
  • Nicholas Wilcken, Department of Medical Oncology, University of Sydney, Westmead Hospital, Wentworthville NSW, Australia
  • Eric P. Winer, Breast Oncology Center, Dana-Farber Cancer Institute, Boston, USA (Chairman)
  • William C. Wood, Department of Surgery, Winship Cancer Institute, Atlanta, USA

appendix 2

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Footnotes

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