12-Year Ipsilateral Breast Invasive Recurrence in 7.5% to 13.4% of Women With Low-Risk DCIS Receiving Surgical Excision Without Radiation
- Among women with low-risk DCIS treated with lumpectomy and no radiotherapy, 12-year rates of ipsilateral breast invasive recurrence were 7.5% in those with low- or intermediate-grade DCIS and 13.4% in those with high-grade DCIS.
- Risk of local recurrence of DCIS or invasive carcinoma in the treated breast increased during follow-up, with no plateau observed.
As reported by Solin et al in Journal of Clinical Oncology, 12-year results from the ECOG-ACRIN E5194 trial indicate that among women with ductal carcinoma in situ (DCIS) with low-risk clinical and pathologic characteristics, surgical excision without radiation therapy was associated with ipsilateral breast invasive recurrence in 7.5% of those with low- or intermediate-grade DCIS and 13.4% of those with high-grade DCIS. Risk increased over time, with no plateau observed.
In the nonrandomized ECOG-ACRIN E5194 study, women with DCIS with low-risk clinical and pathologic characteristics were assigned to two cohorts between April 1997 and October 2002: cohort 1 (n = 561) had low- (50%) or intermediate-grade (50%) DCIS and tumor size ≤ 2.5 cm; cohort 2 (n = 104) had high-grade DCIS and tumor size ≤ 1 cm. Enrollment and cohort assignment were based on clinical and pathology assessment at treating institutions.
All patients underwent surgical excision (lumpectomy) of the primary DCIS tumor and received no radiation therapy. Excision was to have a minimum negative margin width of ≥ 3 mm or no tumor on reexcision. The primary endpoint of the study was an ipsilateral breast event, defined as the first local recurrence of DCIS or invasive carcinoma in the treated breast.
For cohort 1 and cohort 2: Patient ages were ≤ 39 years in 2% and 4%, 40 to 49 in 17% and 20%, 50 to 59 in 30% and 29%, 60 to 69 in 26% and 27%, and ≥ 70 years in 25% and 20%; 93% and 95% were white and 3% and 4% were black; 76% and 72% were postmenopausal; tumor size was ≤ 5 mm in 40% and 27%, 6 to 10 mm in 41% and 59%, and > 10 mm in 19% and 14%; minimum negative margin width was 3 to 4.9 mm in 33% and 27%, 5 to 9.9 mm in 43% and 45%, and ≥ 10 mm in 21% and 24%; 31% and 24% received tamoxifen; 43% and 45% received hormone replacement therapy prior to study entry; and College of American Pathologists (CAP) grade was low, intermediate, and high in 15%, 59% and 26% and in 2%, 24%, and 74%.
Ipsilateral Breast Event Rates
Median follow-up was 12.3 years. A total of 99 ipsilateral breast events were observed (74 in cohort 1 and 25 in cohort 2), including 51 invasive ipsilateral breast events (52%; 39 in cohort 1 and 12 in cohort 2). The 12-year rates of ipsilateral breast event were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003) and the 12-year rates of invasive event were 7.5% and 13.4% (P = .08).
The risks of developing an ipsilateral breast event and an invasive event increased over time through 12 years, with no plateau observed. In cohort 1, rates of developing ipsilateral breast event and invasive ipsilateral breast event were approximately 1.2% and 0.6% per year through year 12. At 12 years, overall survival was 84.0% and 82.8% (P = .96) and the incidence of contralateral breast cancer events was 6.7% and 12.0% (P = .16).
On multivariate analysis, study cohort (hazard ratio [HR] = 1.84, P = .009, for cohort 2 vs 1) and tumor size (HR = 2.11, P = .03, for > 10 mm vs ≤ 5 mm) were significantly associated with occurrence of ipsilateral breast event. Factors that were not significantly associated included age, menopausal status, minimum negative margin width, method of detection, bloody nipple discharge, tamoxifen use, and prior hormone therapy. On multivariate analysis for invasive ipsilateral breast event, cohort was of borderline significance (P = .08), with no other factor being significant.
Findings With CAP Grading
In a subset of 500 patients with central pathology review using current CAP guidelines for DCIS, 12-year rates of ipsilateral breast event were 12.5% for low-grade, 15.1% for intermediate-grade, and 20.6% for high-grade DCIS (P = .16). The 12-year rates for invasive ipsilateral breast event were 5.5%, 6.7%, and 11.7% (P = .19).
The investigators concluded:
[T]his study has demonstrated that the risks of developing an [ipsilateral breast event] and an invasive [ipsilateral breast event] increased over time through 12 years of follow-up, without plateau, for patients with DCIS of the breast who were selected for favorable clinical and pathologic characteristics and treated with surgical excision without radiation. Individual patients and their physicians will need to decide if these 12-year risks are acceptable, and to judge whether or not to add adjuvant treatment after surgical excision. Not all patients and their physicians will agree on what is considered too high a risk of developing an [ipsilateral breast event] or an invasive [ipsilateral breast event] to recommend observation after surgical excision, or what risk is considered too low to justify adding radiation treatment. However, this study provides 12-year data to begin those discussions, and to help inform the treatment decision-making process.