title: High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma.
abstract: OBJECTIVE
  Women with locally unresectable and inflammatory breast carcinoma (IBC) have an approximately 30% 5-year disease-free survival (DFS) rate with conventional multimodality therapy. A short but dose-intensive multimodality phase II trial was designed in an attempt to improve outcome in stage IIIB disease. Mastectomy was performed after high-dose therapy to evaluate pathologic response to treatment.
  
  
  METHODS
  Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support. Local therapy consisted of mastectomy and radiotherapy. Tamoxifen (5 years) was begun if the patient was estrogen receptor-positive (ER+).
  
  
  RESULTS
  Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mastectomy before any systemic therapy (seven with pathologic IBC, three with residual tumor after mastectomy). Eighty percent received full-dose doxorubicin with 60% on schedule. Clinical response rates to induction were 15% complete response (CR), 5% very good partial response (VGPR), 59% partial response (PR), and 21% minor response (MR)/stable disease (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CTCb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30-month DFS is estimated at 100%, 70%, and 38%, respectively. Those with zero, one to three, or > or = four positive nodes at axillary dissection had a median DFS of 31, 18, and 13 months, respectively.
  
  
  CONCLUSIONS
  This short but dose-intensive multimodality approach for stage IIIB breast carcinoma is feasible with encouraging results to date.
authors.affiliation: Department of Cancer Pharmacology, Dana-Farber Cancer Institute, Boston, MA, USA. layash@umich.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Ayash
authors.forename: A
authors.initials: A
authors.lastname: Elias
authors.forename: J
authors.initials: J
authors.lastname: Ibrahim
authors.forename: G
authors.initials: G
authors.lastname: Schwartz
authors.forename: C
authors.initials: C
authors.lastname: Wheeler
authors.forename: E
authors.initials: E
authors.lastname: Reich
authors.forename: C
authors.initials: C
authors.lastname: Lynch
authors.forename: D
authors.initials: D
authors.lastname: Warren
authors.forename: C
authors.initials: C
authors.lastname: Shapiro
authors.forename: P
authors.initials: P
authors.lastname: Richardson
authors.forename: D
authors.initials: D
authors.lastname: Hurd
authors.forename: L
authors.initials: L
authors.lastname: Schnipper
authors.forename: E
authors.initials: E
authors.lastname: Frei
authors.forename: K
authors.initials: K
authors.lastname: Antman
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009367:Neoplasm Staging; D011878:Radiotherapy; D012074:Remission Induction; D015996:Survival Rate; D014182:Transplantation, Autologous
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin