title: Effect of nodal irradiation and fraction size on cardiac and cerebrovascular mortality in women with breast cancer treated with local and locoregional radiotherapy.
abstract: OBJECTIVE
  To determine whether the adjuvant breast cancer radiation volume or fraction size (>2 Gy vs. ≤2 Gy) affected the risk of fatal cardiac or cerebrovascular (CCV) events and to determine whether the addition of regional radiotherapy (RT) increased the risk of fatal cerebrovascular events compared with breast/chest wall RT alone.
  
  
  METHODS
  Overall survival was compared for patients receiving breast/chest wall RT alone or breast/chest wall plus regional node RT (BRCW+NRT) in a population-based cohort of women with early-stage breast cancer who had undergone RT between 1990 and 1996. The effect of laterality, age, systemic therapy, radiation volume, and fraction size on the risk of fatal CCV events was analyzed using a competing risk method.
  
  
  RESULTS
  A total of 4,929 women underwent adjuvant RT. The median follow-up was 11.7 years. BRCW+NRT was associated with an increased risk of CCV death at 12 years (5% for BRCW+NRT vs. 3.5% for breast/chest wall RT alone; p = .004), but the fraction size was not (3.92% for a fraction size >2 Gy vs. 3.54% for a fraction size <2 Gy; p = .83). The 12-year absolute risk of death from stroke alone did not differ for either radiation volume (1.17% for BRCW+NRT vs. 0.8% for breast/chest wall RT alone; p = .22) or fraction size (p = .59).
  
  
  CONCLUSIONS
  Regional RT was associated with a small (1.5% at 12 years), but statistically significant, increased risk of death from a CCV event. The addition of regional RT did not significantly increase the risk of death from stroke, although the number of events was small. An increased fraction size was not significantly associated with a greater risk of fatal CCV events. These data support the continued use of hypofractionated adjuvant regional RT.
authors.affiliation: Division of Radiation Oncology and Developmental Radiotherapeutics, University of British Columbia, Vancouver, BC, Canada. estokes@bccancer.bc.ca
authors.forename: Erika L
authors.initials: EL
authors.lastname: Stokes
authors.forename: Scott
authors.initials: S
authors.lastname: Tyldesley
authors.forename: Ryan
authors.initials: R
authors.lastname: Woods
authors.forename: Elaine
authors.initials: E
authors.lastname: Wai
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Olivotto
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002423:Cause of Death; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000209:etiology / Q000401:mortality*; D006801:Humans; D015182:Lymphatic Irradiation / Q000009:adverse effects* / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000401:mortality; D012189:Retrospective Studies; D012306:Risk; D020521:Stroke / Q000209:etiology / Q000401:mortality*; D016019:Survival Analysis; D055815:Young Adult