title: Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS.
abstract: BACKGROUND
  Ipsilateral breast tumor recurrence (IBTR) is the most common failure event after lumpectomy for ductal carcinoma in situ (DCIS). We evaluated invasive IBTR (I-IBTR) and its influence on survival among participants in two National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized trials for DCIS.
  
  
  METHODS
  In the NSABP B-17 trial (accrual period: October 1, 1985, to December 31, 1990), patients with localized DCIS were randomly assigned to the lumpectomy only (LO, n = 403) group or to the lumpectomy followed by radiotherapy (LRT, n = 410) group. In the NSABP B-24 double-blinded, placebo-controlled trial (accrual period: May 9, 1991, to April 13, 1994), all accrued patients were randomly assigned to LRT+ placebo, (n=900) or LRT + tamoxifen (LRT + TAM, n = 899). Endpoints included I-IBTR, DCIS-IBTR, contralateral breast cancers (CBC), overall and breast cancer-specific survival, and survival after I-IBTR. Median follow-up was 207 months for the B-17 trial (N = 813 patients) and 163 months for the B-24 trial (N = 1799 patients).
  
  
  RESULTS
  Of 490 IBTR events, 263 (53.7%) were invasive. Radiation reduced I-IBTR by 52% in the LRT group compared with LO (B-17, hazard ratio [HR] of risk of I-IBTR = 0.48, 95% confidence interval [CI] = 0.33 to 0.69, P < .001). LRT + TAM reduced I-IBTR by 32% compared with LRT + placebo (B-24, HR of risk of I-IBTR = 0.68, 95% CI = 0.49 to 0.95, P = .025). The 15-year cumulative incidence of I-IBTR was 19.4% for LO, 8.9% for LRT (B-17), 10.0% for LRT + placebo (B-24), and 8.5% for LRT + TAM. The 15-year cumulative incidence of all contralateral breast cancers was 10.3% for LO, 10.2% for LRT (B-17), 10.8% for LRT + placebo (B-24), and 7.3% for LRT + TAM. I-IBTR was associated with increased mortality risk (HR of death = 1.75, 95% CI = 1.45 to 2.96, P < .001), whereas recurrence of DCIS was not. Twenty-two of 39 deaths after I-IBTR were attributed to breast cancer. Among all patients (with or without I-IBTR), the 15-year cumulative incidence of breast cancer death was 3.1% for LO, 4.7% for LRT (B-17), 2.7% for LRT + placebo (B-24), and 2.3% for LRT + TAM.
  
  
  CONCLUSIONS
  Although I-IBTR increased the risk for breast cancer-related death, radiation therapy and tamoxifen reduced I-IBTR, and long-term prognosis remained excellent after breast-conserving surgery for DCIS.
authors.affiliation: Department of Surgery; 300 Pasteur Dr H3625, Stanford University School of Medicine, Stanford, CA 94305-5655. wapnir@stanford.edu.
authors.forename: Irene L
authors.initials: IL
authors.lastname: Wapnir
authors.forename: James J
authors.initials: JJ
authors.lastname: Dignam
authors.forename: Bernard
authors.initials: B
authors.lastname: Fisher
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Anderson
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Julian
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Land
authors.forename: Richard G
authors.initials: RG
authors.lastname: Margolese
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D015986:Confounding Factors, Epidemiologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen