Achievements (2009 - 2010)
The EORTC Breast Cancer Group (BCG) is a multidisciplinary group involving surgeons, medical oncologists, pathologists, radiation oncologists, basic scientists, and clinical research fellows. The main goal of the BCG is to carry high quality international clinical trials covering all areas of breast cancer care, from in situ carcinoma to metastatic disease, and to investigating new anticancer agents in phase I/II trials and therapeutic questions of strategic importance in large phase III trials.
The BCG has recruited a total of over 23.000 patients in clinical trials, including an average of 1015 patients/year over the last 3 years from 60 medical centres. These patients are included not only in EORTC-led studies, but also Inter-Group trials where the EORTC collaborates in trials led by other groups. The EORTC is one of the founding organizations of the Breast International Group (BIG), a worldwide network of breast cancer research groups. Intergroup collaboration is essential as it avoids duplication of efforts and wasting of resources.
The BCG members meet twice a year. Additional teleconferences of the Steering Committee are held every 6 weeks.
Every two years, the group organises the ‘European Breast Cancer Conference’ (EBCC) in collaboration with the European Society of Mastology (EUSOMA) and Europa Donna (the European Breast Cancer Coalition). In March 2008, over 5000 participants from 92 countries attended a highly successful EBCC 6 held in Berlin. This meeting continued the tradition of previous conferences, providing excellent opportunities for dialogue between clinicians, researchers, nurses and patients’ advocates. The aim of these meetings is to create a platform for closer cooperation between the parties in order to stimulate both scientific progress and to provide better standards of care for breast cancer in Europe and beyond. The EBCC 7 will be held in Barcelona, in March 2010.
Over the past several years the EORTC has become increasingly more active in the field of translational research. The BCG has incorporated translational research elements in their protocols. Translational research evaluating correlations between clinical outcomes and biologic tumour characteristics has become a high priority in the group’s strategy.
Examples of such trials are the EORTC 10094 trial and EORTC 10041 trials. The EORTC 10994 p53 trial, an inter-group translational research trial designed and led by the EORTC to assess the potential predictive value of p53 status in patients with locally advanced/inflammatory or large operable breast cancer. This trial prospectively randomised patients for a taxane vs. a non taxane regimen in the neoadjuvant setting. The primary endpoint is progression free survival (PFS), and the secondary endpoints are distant metastasis-free survival, overall survival, pathological complete response and toxicity. This trial has an expected final analysis for the end of 2009.
The EORTC 10041 (MINDACT trial) is a multicentre, prospective, phase III trial which will accrue
6000 early breast cancer patients, either node negative or with 1-3 positive lymph nodes. It compares
the 70-prognostic signature, a genomic test developed with micro-array technology, to traditional
clinical-pathological methods for assessing the risk of breast cancer recurrence in women with early
breast cancer. It is hypothesized that using the genomic test in addition to traditional methods will
result in more accurate risk assessment such that in the future 10-20% of patients could safely avoid
adjuvant chemotherapy and its potential side effects. The MINDACT trial design also includes two
additional questions related to the best treatment in terms of adjuvant chemotherapy and hormone
therapy. The MINDACT trial already reached its first milestone, the “pilot phase” consisting of the
first 800 patients, in November 2008. The preliminary results of this phase demonstrate that the trial
is logistically feasible, that the compliance rate of both physicians and patients is high, and that the
overall process provides good quality data and biological materials. With an average accrual rate of
120 patients per month, the trial is expected to finish recruitment by the end of 2012.
The EORTC trial 10981-22023 AMAROS (After Mapping of the Axilla: Radiotherapy Or Surgery) is a
phase III study comparing a complete axillary lymph node dissection with radiotherapy to the axilla in
sentinel node positive patients, with sentinel node negative patients given no further axillary treatment
but still being followed for the end-points of the study. Patients included have operable invasive
breast cancer greater than 5mm and less than 5 cm without clinically compromised regional lymph
nodes. The main objective of the trial is to provide equivalent local/regional control for patients with
proven axillary lymph node metastasis, as detected by sentinel node biopsy, with reduced morbidity
by treating with axillary radiotherapy instead of axillary lymph node dissection. The study accrued approximately 4000 patients by the end of 2008. Hence, 85% of the required patients are included, and
the trial is expected to finalize the accrual of patients in 2010. A new EORTC trial is planned, which
will succeed the AMAROS trial.
This is the POWER trial, POsitive Sentinel node: Wait & see, Excision or Radiotherapy The aim of
this trial is to analyze the axillary recurrence rate in patients with proven (sub) micrometastases by
sentinel node biopsy if no further axillary therapy is offered.
The EORTC trial 22051 (SUPREMO -Selective use of postoperative radiotherapy after mastectomy) is an InterGroup trial, designed to determine the effect of ipsilateral chest wall irradiation following mastectomy and axillary clearance for women with operable breast cancer at ‘intermediate risk’ of loco-regional recurrence. The primary endpoint is overall survival and chest wall recurrence. The number of patients required is 3700, and the current accrual is about 500 patients. Accrual to date has been slower than anticipated, so that an amendment is planned to enlarge the eligibility criteria. This will extend enrolment to patients with clinical stage T3N0 or T1-2 N0-1 or T1-2 N0 with additional risk factors, patients who have received neoadjuvant systemic therapy, patients carrying BRCA 1 or 2 gene mutations, patients with histologically positive internal mammary sentinel nodes, and patients with pN1 in whom less than 10 lymph nodes were obtained on an axillary clearance. This study prospectively studies the cardiac toxicity of the radiotherapy, and collects tumour samples in order to be able to study biological characteristics of those tumours that do and don’t recur, both with and without radiotherapy.
The EORTC 10054 study (Lapatax) is a phase I/II trial designed to compare the use of Lapatinib, Herceptin and the combination when given in conjunction with Docetaxel during FEC-D neoadjuvant chemotherapy for large operable and locally advanced breast cancer. The phase I part of the study, which determines the recommended doses of Lapatinib and Docetaxel, is expected to close by the summer, 2009, and the 150-patient phase II randomised three-arm study will then open in the autumn, 2009. This study has already demonstrated that it is possible to combine the licensed dose of docetaxel (100mg/m2) with Lapatinib, something not found possible in advanced cancer patients. The study also involves prospective tumour and blood sample collection to provide a resource for translational research.
The EORTC 10071 ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) study is another InterGroup trial. It is a randomised, open label multi-centre phase III study comparing the activity of lapatinib alone versus trastuzumab alone versus trastuzumab followed by lapatinib versus lapatinib concomitantly with trastuzumab in the adjuvant treatment of patients with ErbB2 over expressing and/or amplified breast cancer. The study also has a strong translational research component.