ORIGINAL ARTICLE Long-term survival in patients with metastatic breast cancer receiving intensified chemotherapy and stem cell rescue: data from the Italian registry M Martino 1 , A Ballestrero 2 , A Zambelli 3 , S Secondino 4 , M Aieta 5 , C Bengala 6 , AM Liberati 7 , C Zamagni 8 , M Musso 9 , M Aglietta 10 , R Schiavo 11 , L Castagna 12 , G Rosti 13 , B Bruno 14 and P Pedrazzoli 4 , on behalf of Gruppo Italiano per il Trapianto di Midollo Osseo, Cellule staminali emopoietiche e terapia cellulare (GITMO) – Sezione Tumori Solidi The median survival of women with metastatic breast cancer (MBC) is 18–24 months, and fewer than 5% are alive and disease free at 5 years. We report toxicity and survival in a cohort of MBC patients receiving high-dose chemotherapy (HDC) with autologous hematopoietic SCT (AHSCT) in Italy between 1990 and 2005. Data set for survival analysis has been obtained for 415 patients. Clinical parameters including probability of transplant-related mortality (TRM), PFS and OS. With a median follow-up of 27 months (range 0–172), OS and PFS at 5 and 10 years in the whole population were 47/23 and 32/14%, respectively. A total 239 patients are alive with a median follow-up of 33 months (range 2–174). Survival was significantly more pronounced in patients harboring hormone receptor positive tumors (P ¼ 0.028), without visceral metastases (P ¼ 0.009) and in women with chemosensitive disease (Po0.0001). Sixty eight patients (20.4%) who received HDC in partial response, stable or progressive disease underwent conversion to CR. TRM was 2.5% overall and 1.3% since 2000. Our findings suggest that could be a role for HDC and AHSCT in delaying disease progression and possibly cure a subset of MBC patient harboring chemosensitive tumors. Bone Marrow Transplantation (2013) 48, 414–418; doi:10.1038/bmt.2012.149; published online 6 August 2012 Keywords: intensified chemotherapy; metastatic breast cancer; stem cell transplantation; toxicity; survival INTRODUCTION Metastatic breast cancer (MBC) remains a leading cause of cancer death in western countries. Despite advances in diagnosis and treatment, the median survival of women with MBC that is no longer hormonally responsive or is estrogen receptor (ER)- negative is 18–24 months, and fewer than 5% are alive and disease free at 5 years. 1–3 Throughout the 1980s and early 1990s, reports suggested that long-term disease-free survival (DFS) could be achieved with high-dose chemotherapy (HDC) using alkylating-agent combina- tions supported by autologous hematopoietic stem cell trans- plantation (AHSCT). 4–7 By the mid-1990s, breast cancer (BC) had become the most common indication for AHSCT in North America and Europe. Phase II studies created positive expectations among physicians and their patients, to such an extent that HDC with AHSCT became widely used as a therapeutic option also outside the controlled trials. 8,9 The use of PBSC as a source of progenitor cells, instead of BM for transplant, 10 significantly reduced the morbidity and mortality, related to HDC and allowed the utilization of this procedure outside specialized or academic centers. There followed a phase of disillusion after reports of some randomized studies not showing significant OS benefit of HDC 11–16 and after a case of scientific misconduct. 17 The scene was prematurely set for the demise of HDC in BC and, in more recent years, the number of procedures has diminished and, in fact, abandoned by the vast majority of Centers. Retrospective studies have shown that younger BC patients with limited tumor load or with highly sensitive disease may benefit from intensified chemotherapy. 18–21 It comes out clearly from most of the prospective studies and from a large EBMT (European Group for Blood and Marrow Transplantation) retrospective analysis 22 that 15–30% of patients undergoing HDC after achieving CR from conventional treatments are long- term (45 years) disease-free survivors. New information provided from phase III trials 23–25 suggests that HDC may still have a role in subgroups of patients with BC, both in the adjuvant setting and for metastatic disease mainly when risk factors and biological parameters are considered. Recently meta-analyses obtained individual patient data from 15 adjuvant and 6 MBC randomized trials that compared HDC to a control therapy without stem-cell support. 26,27 In both the settings, HDC achieved a statistically significant improvement in EFS but without a significant improvement in OS. 1 Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera BMM, Reggio Calabria, Italy; 2 Department of Medicine, University of Genoa, Genova, Italy; 3 Medical Oncology Unit, IRCCS Salvatore Maugeri Foundation, Pavia, Italy; 4 Medical Oncology Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy; 5 Medical Oncology Unit, Casa Sollievo della Sofferenza, S. Giovanni Rotondo, FG, Italy; 6 Medical Oncology Unit, University of Modena, Modena, Italy; 7 Department of Oncology and Hematology, University of Perugia, Terni, Italy; 8 Medical Oncology Unit, Azienda Ospedaliera S. Orsola-Malpighi, Bologna, Italy; 9 Hematology and Bone Marrow Transplant Unit ‘La Maddalena’, Palermo, Italy; 10 Medical Oncology Unit, Institute for Cancer Research and Treatment, Candiolo, TO, Italy; 11 Medical Oncology Unit ‘Falck’, Ospedale Niguarda Ca’ Granda, Milano, Italy; 12 Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano MI, Italy; 13 Medical Oncology Unit, Ospedale Ca’ Foncello, Treviso, Italy and 14 National Registry GITMO & Data Managing, Ospedale San Martino, Genova, Italy. Correspondence: Dr M Martino, Hematology and Bone Marrow Transplant Unit, Department of Oncology and Hematology, Azienda Ospedaliera BMM, Via Cantaffio, 89133 Reggio Calabria, Italy. E-mail: maxmartino65@alice.it Received 8 March 2012; revised 3 July 2012; accepted 4 July 2012; published online 6 August 2012 Bone Marrow Transplantation (2013) 48, 414–418 & 2013 Macmillan Publishers Limited All rights reserved 0268-3369/13 www.nature.com/bmt