title: Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial.
abstract: BACKGROUND
  The British Columbia randomized radiation trial was designed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node-positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy. Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy (37.5 Gy in 16 fractions). Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance. We report the analysis of data from the 20-year follow-up.
  
  
  METHODS
  Survival was analyzed by the Kaplan-Meier method. Relative risk estimates were calculated by the Wald test from the proportional hazards regression model. All statistical tests were two-sided.
  
  
  RESULTS
  At the 20 year follow up (median follow up for live patients: 249 months) chemotherapy and radiation therapy, compared with chemotherapy alone, were associated with a statistically significant improvement in all end points analyzed, including survival free of isolated locoregional recurrences (74% versus 90%, respectively; relative risk [RR] = 0.36, 95% confidence interval [CI] = 0.18 to 0.71; P = .002), systemic relapse-free survival (31% versus 48%; RR = 0.66, 95% CI = 0.49 to 0.88; P = .004), breast cancer-free survival (48% versus 30%; RR = 0.63, 95% CI = 0.47 to 0.83; P = .001), event-free survival (35% versus 25%; RR = 0.70, 95% CI = 0.54 to 0.92; P = .009), breast cancer-specific survival (53% versus 38%; RR = 0.67, 95% CI = 0.49 to 0.90; P = .008), and, in contrast to the 15-year follow-up results, overall survival (47% versus 37%; RR = 0.73, 95% CI = 0.55 to 0.98; P = .03). Long-term toxicities, including cardiac deaths (1.8% versus 0.6%), were minimal for both arms.
  
  
  CONCLUSIONS
  For patients with high-risk breast cancer treated with modified radical mastectomy, treatment with radiation therapy (schedule of 16 fractions) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone, and it is well tolerated, with acceptable long-term toxicity.
authors.affiliation: McGill University Health Center, Royal Victoria Hospital, 687 Pine Ave., Montreal, PQ, Canada H3A 1A1. joseph.ragaz@mcgill.ca
authors.forename: Joseph
authors.initials: J
authors.lastname: Ragaz
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Olivotto
authors.forename: John J
authors.initials: JJ
authors.lastname: Spinelli
authors.forename: Norman
authors.initials: N
authors.lastname: Phillips
authors.forename: Stewart M
authors.initials: SM
authors.lastname: Jackson
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Wilson
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Knowling
authors.forename: Christopher M L
authors.initials: CM
authors.lastname: Coppin
authors.forename: Lorna
authors.initials: L
authors.lastname: Weir
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.forename: Nhu
authors.initials: N
authors.lastname: Le
authors.forename: Ralph
authors.initials: R
authors.lastname: Durand
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Coldman
authors.forename: Mohamed
authors.initials: M
authors.lastname: Manji
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D001955:British Columbia; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000528:radiation effects*; D008207:Lymphatic Metastasis; D015411:Mastectomy, Modified Radical; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate