Recent Achievements
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 goals of the BCG are to carry high quality international clinical trials covering all areas of breast cancer care from in situ carcinoma to metastatic disease, to investigate new anticancer agents in phase I/II trials, and to ask therapeutic questions of strategic importance in large phase III trials.
The BCG has recruited a total of over 4000 patients into clinical trials including an average of 1340 patients per year over the last three years from 57 medical centers. These patients are included not only in EORTC studies but also in intergroup trials in which the EORTC collaborates.
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 six weeks.
Every two years, the BCG organizes 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 2010, over 5000 participants from 96 countries attended the highly successful 7th EBCC held in Barcelona. This meeting continued the tradition of previous conferences by providing excellent opportunities for dialogue between clinicians, researchers, nurses, and patient 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 provide better standards of care for breast cancer in Europe and beyond. EBCC 8 will be held in Vienna in March 2012.
Over the past several years the EORTC has become increasingly active in the field of translational research, and the BCG has actively incorporated translational research elements in their protocols. In particular, translational research evaluating correlations between clinical outcomes and biologic tumor characteristics has become a high priority in the strategy of the BCG.
Examples of trials with a strong translational research component are the EORTC 10994 and EORTC 10041 trials. The EORTC 10994 p53 trial is an intergroup 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 randomized 1856 patients to test the hypothesis that neoadjuvant taxane regimen confers a greater advantage over anthracycline regimen in p53 mutated tumors than in p53 wild type tumors. The results of this trial were presented at ASCO 2010. At a median follow up of 57 months, p53 did not demonstrate to be a predictive factor of response or resistance to taxanes; however, the prognostic value of p53 in early breast cancer has been confirmed.
The EORTC 10041 trial (MINDACT) is a multicentre, prospective, phase III trial which will accrue 6000 early stage 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 so 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 best treatment in terms of adjuvant chemotherapy and
hormone therapy. The MINDACT trial already reached its first milestone in November 2008 by accruing the first 800 patients, the “pilot phase”. The preliminary results of this phase, presented at EBCC 2010, 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 195 patients per month in the last six months, the trial is expected to finish recruitment by mid 2011.
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, and 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 completed accrual on April 2010 with 4,828 patients included. A new EORTC trial is planned which will follow 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 22051 trial (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 1600, and the current accrual is approximately 810 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 one or two gene mutations, patients with histologically positive internal mammary sentinel nodes, and patients with pN1 in whom less than ten lymph nodes were obtained on an axillary clearance. This study prospectively studies the cardiac toxicity of the radiotherapy and collects tumor samples in order to be able to study biological characteristics of those tumors that do and do not recur both with and without radiotherapy.
The EORTC 10054 trial (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 determines the recommended doses of Lapatinib and Docetaxel. The dose determination study has confirmed that with primary prophylactic G-CSF, docetaxel 100 mg/m2 can be safely and effectively given with lapatinib 1,250 mg daily continuously. Prior to treatment, frozen tumor and blood samples were taken to better define which tumors were particularly sensitive to either trastuzumab and/or lapatinib. The phase II part of the study was opened in October 2010. It will enroll 150 patients from European centers into a three- arm randomized trial whose primary endpoint is pathological complete response. All patients will receive FEC-D before primary surgery: three cycles of FEC (without anti-HER2 therapy) followed by three cycles of docetaxel plus either trastuzumab (conventional weekly schedule), monotherapy with lapatinib, or the combination of trastuzumab and lapatinib.
The EORTC 10071 ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial is also an intergroup trial. It is a randomized, open label multi-center 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 number of patients required is 8,400 and the current accrual is about 8,000 patients. The study also has a mandatory translational research component with collection of paraffin-embedded tumor tissue for central pathology review and blood samples after surgery for genomic DNA.