Page, David L.

1005 Background: We previously reported that in the E5194 clinical trial patients with ductal carcinoma in situ (DCIS) treated with wide local excision (WLE) without radiation (RT), the DCIS Score was significantly associated with 10 year risk of an ipsilateral breast event (IBE - recurrence of in situ or invasive carcinoma), whether evaluated as a continuous or categorical variable (P=0.02 for both). Here we evaluate correlation between DCIS Score and clinicopathologic (CP) features and if DCIS Score provides independent recurrence risk information. Methods: The study population included 327 women with DCIS prospectively selected for treatment with WLE without RT, including low-intermediate grade tumors ≤2.5 cm or high-grade ≤1 cm. CP variables included age, menopausal status, tamoxifen treatment (used in 29%) and expert centrally determined tumor size, grade, comedo necrosis, tumor type, and margin status. The association between DCIS Score and CP variables was examined by spearman rank correlation, and proportional hazards regression models were used to determine variables significantly associated with IBE. Results: Lesion size (p=0.009) and menopausal status (p=0.03) were significantly associated with IBE, while grade (p=0.69) and comedo necrosis (p=0.47) were not. DCIS Score was significantly associated with IBE after adjustment for CP features and tamoxifen use (p=0.02). DCIS Score was moderately correlated with grade (rs=0.46; 95% CI 0.37,0.54), percentage comedo necrosis (rs=0.49; CI 0.41,0.57), and lesion size (rs=0.18; CI 0.08,0.29) but not other features. Exploratory analyses in all CP subgroups, including the multicomponent Van Nuys Prognostic Index, showed a wide range of DCIS Scores in each subgroup. Concordance of the grades among readers was low: local vs parent central, 68%; local vs central nuclear grade, 45%; parent central vs central nuclear grade, 37%. Conclusions: DCIS Score is moderately correlated with grade, comedo necrosis, and tumor size. DCIS Score provides recurrence risk information independent of these features and identifies subjects with DCIS who are at high risk for local invasive and in-situ local recurrence after WLE alone.

BACKGROUNDWomen with atypical hyperplasia (AH) on breast biopsy have a substantially increased risk of breast cancer (BC). Here the BC risk for the extent and subtype of AH is reported for 2 separate cohorts.METHODSAll samples containing AH were included from 2 cohorts of women with benign breast disease (Mayo Clinic and Nashville). Histology review quantified the number of foci of atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH). The BC risk was stratified for the number of AH foci within AH subtypes.RESULTSThe study included 708 Mayo AH subjects and 466 Nashville AH subjects. In the Mayo cohort, an increasing number of foci of AH was associated with a significant increase in the risk of BC both for ADH (relative risks of 2.61, 5.21, and 6.36 for 1, 2, and ≥3 foci, respectively; P for linear trend = .006) and for ALH (relative risks of 2.56, 3.50, and 6.79 for 1, 2, and ≥3 foci, respectively; P for linear trend = .001). In the Nashville cohort, the relative risks of BC for ADH were 2.70, 5.17, and 15.06 for 1, 2, and ≥3 foci, respectively (P for linear trend < .001); for ALH, the relative risks also increased but not significantly (2.61, 3.48, and 4.02, respectively; P = .148). When the Mayo and Nashville samples were combined, the risk increased significantly for 1, 2, and ≥3 foci: the relative risks were 2.65, 5.19, and 8.94, respectively, for ADH (P < .001) and 2.58, 3.49, and 4.97, respectively, for ALH (P = .001).CONCLUSIONSIn 2 independent cohort studies of benign breast disease, the extent of atypia stratified the long‐term BC risk for ADH and ALH. Cancer 2016;122:2971‐2978. © 2016 American Cancer Society.

PurposeTo determine the risk of ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) treated with local excision without irradiation.Patients and MethodsPatients with either low- or intermediate-grade DCIS measuring 2.5 cm or smaller, or high-grade DCIS measuring 1 cm or smaller who had microscopic margin widths of 3 mm or wider and no residual calcifications on postoperative mammograms were eligible for a prospective trial conducted from 1997 to 2002 by the Eastern Cooperative Oncology Group and North Central Cancer Treatment Group. Patients entered in 2000 and later could take tamoxifen if they wished. Median age at last surgery for the entire population was 60 years (range, 28 to 88 years), and median tumor sizes in the two strata were 6 mm and 5 mm, respectively.ResultsWith a median follow-up of 6.2 years, the 5-year rate of ipsilateral breast events in the 565 eligible patients in the low/intermediate grade stratum was 6.1% (95% CI, 4.1% to 8.2%). With a median follow-up of 6.7 years, this incidence for the 105 eligible patients in the high-grade stratum was 15.3% (95% CI, 8.2% to 22.5%).ConclusionRigorously evaluated and selected patients with low- to intermediate-grade DCIS with margins 3 mm or wider had an acceptably low rate of ipsilateral breast events at 5 years after excision without irradiation. Patients with high-grade lesions had a much higher rate, suggesting that excision alone is inadequate treatment. Further follow-up is necessary to document long-term results.