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.

Figure 1

CONSORT diagram for National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 and NSABP B-24 trials. Patients with no follow-up information after random assignment were excluded from the analysis. LO = lumpectomy only; LRT = lumpectomy followed by radiation therapy; LRT + placebo = LRT plus 5 years of placebo; LRT + TAM = LRT plus 5 years of tamoxifen.

Figure 2

Effects of radiation and tamoxifen on cumulative incidence of breast cancer events. A) Invasive ipsilateral breast tumor recurrences (I-IBTR), B) ductal carcinoma in situ–ipsilateral breast tumor recurrences (DCIS-IBTR), and C) all contralateral breast cancers (CBC). Data are shown by trial (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-17 and NSABP B-24) and treatment group—lumpectomy only (LO), lumpectomy followed by radiation therapy (LRT), and lumpectomy with radiation therapy plus 5 years of placebo (LRT + placebo) or tamoxifen (LRT+TAM). CI = confidence interval.

Figure 3

Effects of radiation and tamoxifen on cumulative incidence of invasive ipsilateral breast tumor recurrences (I-IBTR) by age at diagnosis. A) Patients younger than 45 years, B) patients aged 45–54 years, C) patients aged 55–64 years, and D) patients 65 years and older. Data are shown by trial (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-17 and NSABP B-24) and treatment group—lumpectomy only (LO), lumpectomy with radiation therapy (LRT), and lumpectomy with radiation therapy plus 5 years of placebo (LRT + placebo) or tamoxifen (LRT + TAM).

Figure 4

Cumulative incidence of invasive ipsilateral breast tumor recurrences within categories of margin status and treatment in the National Surgical Adjuvant Breast and Bowel Project B-24 trial. Treatment groups were lumpectomy with radiation therapy plus 5 years of placebo (LRT + placebo) or tamoxifen (LRT + TAM), without tumor at margins, or with involved or unknown tumor at margins as defined in the B-24 trial.

Figure 5

Cumulative incidence of deaths. A) Deaths attributed to breast cancer. B) Deaths attributed to other causes. Data are shown by trial (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-17 and NSABP B-24) and treatment group—lumpectomy only (LO), lumpectomy followed by radiation therapy (LRT), and lumpectomy with radiation therapy plus 5 years of placebo (LRT + placebo) or tamoxifen (LRT + TAM). CI = confidence interval.

Figure 6

Cumulative incidence of breast cancer deaths after invasive ipsilateral breast tumor recurrences (I-IBTR) or ductal carcinoma in situ (DCIS)-IBTR. The patient cohort includes 263 patients with a prior I-IBTR and 227 patients with a prior DCIS-IBTR as a first failure event.