title: Adjuvant high-dose chemotherapy with autologous hematopoietic stem cell support for high-risk primary breast cancer: results from the Italian national registry.
abstract: The efficacy of high-dose chemotherapy (HDC) and autologous hemopoietic progenitor cell transplantation (AHPCT) for breast cancer (BC) patients has been an area of intense controversy among the medical oncology community. The aim of this study was to assess toxicity and efficacy of this procedure in a large cohort of high-risk primary BC patients who underwent AHPCT in Italy. A total of 1183 patients receiving HDC for high-risk BC (HRBC) (>3 positive nodes) were identified in the Italian registry. The median age was 46 years, 62% of patients were premenopausal at treatment, 60.1% had endocrine-responsive tumors, and 20.7% had a human epidermal growth factor receptor 2 (HER2)-positive tumor. The median number of positive lymph nodes (LN) at surgery was 15, with 71.5% of patients having ≥ 10 positive nodes. Seventy-three percent received an alkylating agent-based HDC as a single procedure, whereas 27% received epirubicin or mitoxantrone-containing HDC, usually within a multitransplantation program. The source of stem cells was peripheral blood in the vast majority of patients. Transplantation-related mortality was .8%, whereas late cardiac and secondary tumor-related mortality were around 1%, overall. With a median follow-up of 79 months, median disease-free and overall survival (OS) in the entire population were 101 and 134 months, respectively. Subgroup analysis demonstrated that OS was significantly better in patients with endocrine-responsive tumors and in patients receiving multiple transplantation procedures. HER2 status did not affect survival probability. The size of the primary tumor and number of involved LN negatively affected OS. Adjuvant HDC with AHPCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk primary BC. Our results suggest that this treatment modality should be proposed in selected HRBC patients and further investigated in clinical trials.
authors.affiliation: Medical Oncology, IRCCS Foundation, San Matteo Hospital, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pedrazzoli
authors.affiliation: Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Medical Oncology, IRCCS Foundation, National Cancer Institute, Milan, Italy.
authors.forename: Alessandro Massimo
authors.initials: AM
authors.lastname: Gianni
authors.affiliation: Medical Oncology, IRCCS Maugeri Foundation, Pavia, Italy.
authors.forename: Gian Antonio
authors.initials: GA
authors.lastname: Da Prada
authors.affiliation: Department of Internal Medicine, University Hospital, Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ballestrero
authors.affiliation: Medical Oncology, Civil Hospital, Ravenna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rosti
authors.affiliation: Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Frassineti
authors.affiliation: Medical Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Aieta
authors.affiliation: Medical Oncology, Niguarda Ca', Granda Hospital, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Secondino
authors.affiliation: Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinieri
authors.affiliation: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera "BMM", Reggio Calabria, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fedele
authors.affiliation: Medical Oncology, University Hospital, Pisa, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bengala
authors.affiliation: Hematology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bregni
authors.affiliation: Medical Oncology, IRCCS Foundation, San Matteo Hospital, Pavia, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Grasso
authors.affiliation: Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
authors.affiliation: Section of Hematology and Bone Marrow Transplant Unit, Cremona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lanza
authors.affiliation: Hematology Unit, Humanitas Cancer Center, Rozzano, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Castagna
authors.affiliation: National Registry GITMO & Data Managing, Ospedale San Martino, Genova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bruno
authors.affiliation: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera "BMM", Reggio Calabria, Italy. Electronic address: dr.massimomartino@gmail.com.
authors.forename: Massimo
authors.initials: M
authors.lastname: Martino
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D015870:Gene Expression; D006801:Humans; D007558:Italy; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D012042:Registries; D012306:Risk; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015251:Epirubicin; D008942:Mitoxantrone; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Autologous hematopoietic progenitor cell support; High-dose chemotherapy; High-risk breast cancer