Prediction of response to primary chemotherapy for operable breast cancer |
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| Institution: | 1. Department of Medicine and Radiotherapy, Istituto Europeo di Oncologia, Via Ripamonti 435, 2041, Milan, Italy;2. Division of Pathology and Laboratory Medicine, Istituto Europeo di Oncologia, Via Ripamonti 435, 2041, Milan, Italy;3. Division of Epidemiology and Biostatistics, Istituto Europeo di Oncologia, Via Ripamonti 435, 2041, Milan, Italy;4. Division of Senology, Istituto Europeo di Oncologia, Via Ripamonti 435, 2041, Milan, Italy;1. Department of Surgery, University of Washington, Seattle, Washington;2. Clinical & Translational Research, Seattle Children’s Hospital, Seattle, Washington;3. Department of Health Services, University of Washington, Seattle, Washington;1. Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands;2. Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands;3. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands;4. Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands;5. Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands;1. Department of Pharmacology and Toxicology, University of Navarra, C/Irunlarrea 1, 31009 Pamplona, Spain;2. VITO-Sustainable Health, Boeretang 200, 2400 Mol, Belgium;3. Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium;4. ISA Lille – LGCgE, University of Lille Nord de France, 48 boulevard Vauban, 59046 Lille, France;5. IdiSNA, Navarra Institute for Health Research, Spain |
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| Abstract: | The use of primary systemic cytotoxics leads to a high remission rate in patients with breast cancer. Response was identified as an important variable associated with survival. Thus, features which predict response, are potentially relevant for planning treatments and improving survival. Retrospectively, we investigated several histopathological features (expression of oestrogen and progesterone receptors, Mib1, bcl-2, c-erbB-2, and p53) prior to two programmes of either sequential preoperative chemotherapy (doxorubicin plus cyclophosphamide) and radiotherapy (Group A), or preoperative chemotherapy (5-fluorouracil, folinic acid and vinorelbine) alone (Group B) in patients with operable breast cancer. After three courses, patients with a partial or complete response were given a further three courses, which was followed for patients in Group A by radiotherapy 50 Gy plus a boost of 10 Gy. All patients were submitted to surgery after completion of preoperative treatment and pathology material from 73 patients (median age, 49 years, range, 30–70; performance status, 0–1; 68 T2, 5 T3) was obtained. The overall response rate according to radiological and clinical evaluation was 59% (68% for Group A and 49% for Group B). 12 of 14 patients with p53-positive tumours and 31 of 59 with p53-negative tumours responded (P=0.04). 6 of 7 patients with elevated c-erbB-2 had a response compared with 37 of 66 patients in the group with c-erbB-2 negative tumours (P=0.03). Mib1 expression decreased substantially (≥50%) in 25 patients during treatment, of whom 20 responded compared with 21 of 48 patients with a lower decrease (P=0.04). Response was observed in 28 of 37 patients with high baseline Mib1 (>20%) and in 15 of 36 patients in the low Mib1 group (P=0.05). Finally, 32 of 44 tumours with low expression of progesterone receptors responded compared with 11 of 29 tumours with high receptors expression (P=0.05). These markers might be useful for tailoring primary and postsurgical systemic treatments. |
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