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

A. Goldhirsch; E. P. Winer; A. S. Coates; R. D. Gelber; M. Piccart-Gebhart; B. Thürlimann; H.-J. Senn; Panel members

Ann Oncol. 2013;24(9):2206-2223.

Breast Cancer Subtypes

The clinico-pathological surrogate definitions of subtypes as adopted by the Panel are summarized in Table 2, and their broad implications for systemic treatment selection are described in Table 3.

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,^[100–104] 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 2 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.

1 2 3 4

Next Section

Table 1. Recent research findings presented at the 13th International Conference on Primary Therapy of Early Breast Cancer and their implications for patient care
Field or treatment	Status of research/implications for patient care
Targeted treatments	Proof of concept of mTOR pathway inhibition in metastatic disease was provided by the Bolero study.¹⁰ The PI3K-alpha inhibitors, such as GDC-0032, have shown strong interaction with ER signalling in laboratory studies. Another PI3K-alpha inhibitor, BYL719, showed preclinical evidence of synergy with fulvestrant. The strong preclinical evidence for favourable interaction between endocrine therapy and various inhibitors of the PI3 kinase pathway (AKT inhibitors or MEK inhibitors) points to the need for clinical trials of such combinations.¹¹ In triple-negative breast cancer, PI3K inhibition impairs BRCA1/2 expression, thus sensitizing cells to PARP inhibition.^{12, 13}
	A frequently mutated gene is TP53, which is abnormal in the majority of cases of HER2 overexpressing and triple-negative disease.^{2, 14} Although, p53 has been studied for decades, its clinical utility remains limited due to the absence of standardization and the heterogeneity of the studies. Wild-type p53 activity impairs the preclinical response to anthracyclines,¹⁵ and there is an interaction with ER such that ER prevents p53-dependent apoptosis.¹⁶ However, p53 was not predictive of preferential sensitivity to an anthracycline-based versus a taxane-based chemotherapy in a large phase III neoadjuvant study.¹⁷
Messages from the EBCTCG Overview	The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis showed efficacy of adjuvant chemotherapy compared with no chemotherapy, superiority of anthracycline-based regimens over CMF and of taxane-containing regimens over those based on anthracycline. The relative magnitude of benefit from anthracycline or anthracycline-taxane combinations resulted in similar reductions of breast cancer mortality irrespective of age, stage, histopathological grade and ER status, although the absolute gain for a low disease burden Luminal A-type of cancer will be very small.^{18, 19}
Mutational analysis of breast cancer	Detailed analysis of the entire genome of breast cancers offers the potential for more precisely personalizing therapy.²⁰ Application is currently limited by the availability of suitably targeted therapeutic agents and by limited understanding of the roles and functions of many of the identified abnormalities, and clarification of which genomic alterations are functional and which are merely passenger mutations.
Personalizing treatment	Analytic validity, clinical (or biologic) validity, and clinical utility are all required for optimal clinical application of tumour biomarkers.²¹
Intrinsic subtypes	Identification of intrinsic subtypes is most precise using molecular technologies.²² Where such assays are unavailable, surrogate definitions of subtype can be obtained by IHC measurements of ER, PgR, Ki-67 and HER2 with in situ hybridization confirmation, where appropriate.²³ Moderate or strong expression of PgR has been proposed as an additional restriction in the surrogate definition of 'Luminal A-like' disease.²⁴ Ki-67 level as a marker of proliferation is also important for this distinction.²³ Both of these markers require quality control. In particular, Ki-67 measurement is not currently standardized among laboratories^25–27 (see panel deliberations below).
Lifestyle issues	Epidemiological evidence suggests that a 'Mediterranean' diet is associated with a modest reduction in the risk of the occurrence of breast cancer.²⁸ Several recent meta-analyses have confirmed the association of physical activity with reduced breast cancer incidence and improved prognosis.²⁹
Hormonal influences	Sex hormones, particularly estrogens, are recognized as important in defining the risk of occurrence of breast cancer, and may be important in particular treatment situations, such as the use of aromatase inhibitors. However, analytical issues still limit the measurement of estrogen at low but clinically relevant levels.^{30, 31}
Hereditary breast cancer	Factors to be considered regarding recommendation for genetic testing include known mutation in the family, patient or close relative with breast cancer diagnosis <35, patient or close relatives with ovarian or fallopian tube cancers, multiple pancreatic cancers, and some pathological features. However, intrinsic subtype cannot safely be used to exclude the need for genetic testing.³²
Obesity and fat	Obesity is widely recognized as a risk factor for both occurrence and worsened prognosis of breast cancer.³³ Obesity is not clearly predictive of AI (versus Tam) benefit in postmenopausal women,^34–36 but may be predictive of reduced AI benefit in premenopausal women.³⁷
	Evidence exists that adipose tissue contains pluripotent stem cells, which might be responsible for tumour angiogenesis.^{38, 39} Such cells have been shown to promote breast cancer growth in preclinical models,⁴⁰ raising the hypothetical concern that use of adipose tissue in breast reconstruction might increase the risk of recurrence.
Metastasis, microenvironment, bone and bisphosphonates	Metastasis is a complex event governed by host interactions. Characteristics of the microenvironment are important in the metastatic process. In preclinical models, tenascin C promotes the aggressiveness of metastasis⁴¹ and autocrine tenascin C is required for early colonization.⁴²
	Bisphosphonates may have beneficial effects in estrogen-deprived women.^43–45 This benefit, which remains uncertain, does not appear to be limited to the inhibition of bone metastases.
Metronomic chemotherapy	Metronomic chemotherapy demonstrates activity in the neoadjuvant setting⁴⁶ and in preclinical studies is effective in combination with anti-angiogenic treatments.⁴⁷
Risk assessment and prediction	Use of genomic prognostic tests is increasing and has led to altered treatment recommendations in 25%–30% of cases. This has been associated with an overall decreased use of adjuvant chemotherapy.⁴⁸ One prospective non-randomized cohort study confirmed the prognostic value of the 70-gene signature in terms of 5-year distant recurrence free interval, and noted an excellent outcome for patients classified as 'low risk' and treated without cytotoxic therapy.⁴⁹ ER and proliferation define cohorts of patients with early and late recurrence risks. It is noteworthy that first-generation tests are largely calibrated on early recurrence, while the risk of recurrence in luminal disease persists for many years and may be better addressed by newer assays.^50–53
	Following neoadjuvant chemotherapy, assessment of residual tumour burden appears prognostically useful, but validation and standardization of this as a prognostic marker is just as important as for IHC or molecular assays.⁵⁴ Residual disease after neoadjuvant chemotherapy appears less important in patients with Luminal A or hormone receptor positive, HER2-positive disease, but pCR seems to be prognostically highly important for non-luminal HER2-positive and triple-negative disease.⁵⁵
	Following conventional adjuvant therapy, definition of residual risk may guide the need for further treatment or clinical trials. While baseline tumour staging and conventional biological parameters are important, further information may be obtained from evaluations including genomic signatures and tumour infiltrating lymphocytes.^56–58
Immunity and vaccines	Therapeutic vaccination remains elusive because of tumour heterogeneity and immune escape mechanisms. Agents, such as ipilimumab, which suppress regulatory T cells, may tip the immune balance to cause tumour regression.⁵⁹ The presence of tumour-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy.⁶⁰ In node-positive, ER-negative, HER2-negative breast cancer, increasing lymphocytic infiltration is associated with an excellent prognosis.⁵⁶
Surgery of the primary	Although the risk of local regional relapse is related to the biological aggressiveness of the disease as reflected in its intrinsic subtype, there is no evidence that more extensive surgery will overcome this risk.⁶¹ Effective systemic therapy decreases loco-regional recurrence.⁶² Not all women prefer breast conservation. For those who do, the only absolute contraindications are positive margins after multiple resections, and the inability to deliver indicated radiotherapy.^{63, 64}
Surgery of the axilla	Substantial new data were presented about the role of and necessity for completion axillary dissection after positive sentinel nodes for patients with clinically node-negative disease. The IBCSG 23-01 trial found no benefit of axillary dissection in patients with micrometastatic disease in one or more sentinel lymph nodes.⁶⁵ There was increasing acceptance of the omission of axillary dissection also in patients similar to those included in the ACOSOG Z0011 trial that is with one or two involved nodes following breast conservation surgery with whole breast radiation therapy.⁶⁶ Ongoing studies are examining the omission of even sentinel node biopsy in patients with ultrasound negative axilla, but this practice remains experimental.⁶⁷
Radiation therapy	Clinical trial evidence supports the validity of hypofractionated radiotherapy such as 40 Gy in 15 or 42.5 Gy in 16 fractions in many patients.^68–70 Such short course whole breast radiation therapy has obvious advantages in terms of patient convenience and cost.
	Trials have demonstrated the safety and efficacy of some forms of partial breast irradiation in selected patients. The main questions are around the definition of a suitable group and variability of levels of evidence between several available intraoperative and postoperative partial breast techniques.⁷¹ ASTRO⁷² and ESTRO.⁷³ provide similar guidelines based on factors such as age, BRCA 1/2, tumour size, margins, ER status, focality, histology, nodal factors, and neoadjuvant therapy. A number of large randomised clinical trials of partial breast irradiation await formal reporting and publication of mature outcome data. Partial breast re-irradiation following 'in breast tumour recurrence' can be considered as an alternative to salvage mastectomy in selected cases, although the long-term safety and efficacy of this approach have not been established.⁷⁴
Adjuvant chemotherapy	A major unresolved question is the threshold for use of adjuvant cytotoxic chemotherapy for patients with Luminal A or Luminal B disease. In prospective/retrospective studies, the 21- gene recurrence score (RS) identifies groups who do not benefit from the addition of chemotherapy in node-negative⁷⁵ or node-positive⁷⁶ disease. In both these studies based on randomised trials, chemotherapy benefit was confined to the group with high 21-gene RS. Another series using the 70-gene signature noted excellent 5-year distant recurrence free interval for the 'good prognosis' group without chemotherapy.⁴⁹ PAM50 classification showed no benefit of anthracycline-based chemotherapy (CEF) compared with CMF chemotherapy in patients with either Luminal A or Luminal B disease.⁷⁷
	For patients with triple-negative disease, optimal chemotherapy regimens have not been defined, but evidence supports the inclusion of anthracyclines and taxanes, but not bevacizumab, platinums, capecitabine, or gemcitabine.⁷⁸
	No standard duration of adjuvant chemotherapy has yet been identified for patients with endocrine non-responsive disease.⁷⁹
Neoadjuvant chemotherapy	Because the goals of treatment are the same in terms of ultimate systemic control, the selection of regimen for neoadjuvant chemotherapy generally follows guidelines similar to those applying to the conventional adjuvant setting.⁸⁰
	A risk of recurrence (ROR) score based on PAM50 showed that there were no or very few pathological complete responses to neoadjuvant chemotherapy among patients with low ROR.²² Other neoadjuvant studies have found that a 70-gene good prognosis signature and a low 21-gene RS predict low probability of pCR.^{81, 82}
HER2-targeted therapy	Clinical trial results support a standard duration of adjuvant trastuzumab of one year rather than longer⁷ or shorter.^8,83
Endocrine therapy	For premenopausal women with hormone receptor positive breast cancer, the standard endocrine therapy is based on tamoxifen. Unresolved questions include the necessity for combining ovarian function suppression with tamoxifen, and the possible substitution of an aromatase inhibitor in combination with ovarian function suppression. The SOFT and TEXT trials addressing these questions will report results in the near future^{46, 84}
	Recent evidence from the ATLAS trial suggests that durations of tamoxifen >5 years may be appropriate.⁹ In postmenopausal women with endocrine responsive disease, letrozole therapy administered after 5 years of tamoxifen was established via the MA.17 study.⁸⁵ Recent analyses of this trial suggest that the benefit of letrozole might be even greater for patients who were premenopausal at the time of initial diagnosis but postmenopausal following completion of five years of tamoxifen.⁸⁶
	Adverse effects of aromatase inhibitors limit their use in a substantial proportion of women, and particular concern may exist for those with pre-existing ischaemic cardiovascular disease.^{87, 88}
Young women	Women under 40 years of age have relatively higher incidence of triple-negative and HER2-positive disease.⁸⁹ One study suggests that very young women, aged ≤35, with triple-negative disease may have particularly high likelihood of achieving pCR with neoadjuvant chemotherapy.⁹⁰
	Social issues such as fertility, sexual functioning, and the care of young children may be particularly important for younger women.⁹¹
Follow-up of survivors	A number of studies have failed to show benefit from more, compared with less intensive follow-up investigations. In at least some health care delivery settings, follow-up conducted by oncology nurses is feasible and might be a reasonable alternative to specialist clinical surveillance.⁹²

Table 2. Surrogate definitions of intrinsic subtypes of breast cancer
Intrinsic subtype	Clinico-pathologic surrogate definition	Notes
Luminal A	'Luminal A-like' all of: ER and PgR positive HER2 negative Ki-67 'low'^a Recurrence risk 'low' based on multi-gene-expression assay (if available)^b	The cut-point between 'high' and 'low' values for Ki-67 varies between laboratories.^a A level of <14% best correlated with the gene-expression definition of Luminal A based on the results in a single reference laboratory.[23] Similarly, the added value of PgR in distinguishing between 'Luminal A-like' and 'Luminal B-like' subtypes derives from the work of Prat et al. which used a PgR cut-point of ≥20% to best correspond to Luminal A subtype.[24] Quality assurance programmes are essential for laboratories reporting these results.
Luminal B	'Luminal B-like (HER2 negative)' ER positive HER2 negative and at least one of: Ki-67 'high' PgR 'negative or low' Recurrence risk 'high' based on multi-gene-expression assay (if available)^b	'Luminal B-like' disease comprises those luminal cases which lack the characteristics noted above for 'Luminal A-like' disease. Thus, either a high Ki-67^a value or a low PgR value (see above) may be used to distinguish between 'Luminal A-like' and 'Luminal B-like (HER2 negative)'.
Luminal B	'Luminal B-like (HER2 positive)' ER positive HER2 over-expressed or amplified Any Ki-67 Any PgR
Erb-B2 overexpression	'HER2 positive (non-luminal)' HER2 over-expressed or amplified ER and PgR absent
'Basal-like'	'Triple negative (ductal)' ER and PgR absent HER2 negative	There is an 80% overlap between 'triple-negative' and intrinsic 'basal-like' subtype. Some cases with low-positive ER staining may cluster with non-luminal subtypes on gene-expression analysis. 'Triple negative' also includes some special histological types such as adenoid cystic carcinoma.

^aA majority of the Panel voted that a threshold of ≥20% was indicative of 'high' Ki-67 status. Others, concerned about the high degree of inter-laboratory variation in Ki-67 measurement [26] and the possibility for undertreatment of patients with luminal disease who might benefit from chemotherapy, would use a lower (local laboratory specific) cut-point to define Ki-67 'high' or use multi-gene-expression assay results, if available.
^bThis factor was added during Panel deliberations after circulation of the first draft of the manuscript, to reflect a strong minority view. Although neither the 21-gene RS nor the 70-gene signature was designed to define intrinsic subtypes, a concordance study noted that over 90% of cases with a low RS and almost 80% of those with a 70-gene low-risk signature were classified as Luminal A [95].

Table 3. Systemic treatment recommendations
'Subtype'	Type of therapy	Notes on therapy
'Luminal A-like'	Endocrine therapy is the most critical intervention and is often used alone.	Cytotoxics may be added in selected patients. Relative indications for the addition of cytotoxics accepted by a majority of the Panel included: high 21-gene RS (i.e. >25), if available; 70-gene high risk status, if available; grade 3 disease; involvement of four or more lymph nodes (a minority required only one node). The Panel was almost equally divided as to whether young age (<35 years) per se was an indication to add cytotoxics.
		Studies suggest a wide geographical divergence in the threshold indications for the inclusion of cytotoxics for the treatment of patients with luminal disease.[96]
'Luminal B-like (HER2 negative)'	Endocrine therapy for all patients, cytotoxic therapy for most.
'Luminal B-like (HER2 positive)'	Cytotoxics + anti-HER2 + endocrine therapy	No data are available to support the omission of cytotoxics in this group.
'HER2 positive (non-luminal)'	Cytotoxics + anti-HER2	Threshold for use of anti-HER2 therapy was defined as pT1b or larger tumour or node-positivity.
'Triple negative (ductal)'	Cytotoxics
'Special histological types'^a A. Endocrine responsive	Endocrine therapy
B. Endocrine non-responsive	Cytotoxics	Adenoid cystic carcinomas may not require any adjuvant cytotoxics (if node negative).

^aSpecial histological types: endocrine responsive (cribriform, tubular and mucinous); endocrine non-responsive (apocrine, medullary, adenoid cystic and metaplastic).

Appendix

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