title: Secondary sarcomas after radiotherapy for breast cancer: sustained risk and poor survival.
abstract: BACKGROUND
  Radiotherapy (RT) has been a risk factor for development of soft tissue sarcomas (STS). The objective of the current study was to quantify the risk of STS after RT and surgery for breast cancer (BCa), assess time trends, and compare long-term survival of patients with RT-associated and non-RT-associated angiosarcoma (AS) using the Surveillance, Epidemiology, and End Results (SEER) database.
  
  
  METHODS
  Women with BCa reported to SEER in 1973 to 2003 were included. Kaplan-Meier curves and proportional hazards models, reported as hazards ratios (HR) with 95% confidence intervals (95% CI), were used. Survival of patients who developed RT-associated AS was compared with that of patients with primary AS of the thorax and upper extremities.
  
  
  RESULTS
  The cohort of 563,155 BCa patients was divided into 2 groups: those who received RT (37%) and those who received no RT. RT use increased with time (P<.0001). A total of 948 patients developed STS 1 to 29 years after BCa diagnosis. RT patients had a higher incidence of all STS (31 vs 22 per 100,000 person-years; HR, 1.5 [95% CI, 1.3-1.8]), AS (HR, 7.6; 95% CI, 4.9-11.9), and malignant fibrous histiocytomas (MFH) (HR, 2.5; 95% CI, 1.6-3.9). RT remained a significant predictor after adjustment for covariates (HR, 1.4; 95% CI, 1.2-1.7). Partial mastectomies (HR, 7.1; 95% CI, 3.2-16), RT (HR, 2.2; 95% CI, 1.1-4.3), and lymph node dissections (HR, 2.6; 95% CI, 1.3-5) were found to be independent risk factors for AS. The hazard of STS after RT peaked at 10 years, reaching the non-RT hazard at approximately 23 years. The 5-year survival for STS was 38%. There was no difference in survival noted between RT-induced and non-RT-induced AS.
  
  
  CONCLUSIONS
  RT was found to increase the risk for STS, in particular AS and MFH. Patients who received RT for BCa should be followed closely for >20 years.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Mery
authors.forename: Suzanne
authors.initials: S
authors.lastname: George
authors.forename: Monica M
authors.initials: MM
authors.lastname: Bertagnolli
authors.forename: Chandrajit P
authors.initials: CP
authors.lastname: Raut
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006394:Hemangiosarcoma / Q000556:secondary; D006801:Humans; D015994:Incidence; D015412:Mastectomy, Segmental / Q000401:mortality; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000401:mortality; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D012306:Risk; D018426:SEER Program; D012509:Sarcoma / Q000401:mortality / Q000556:secondary*; D013997:Time Factors