Abstract P2-08-03: Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence and an increased risk of breast cancer mortality in women with ductal carcinoma in situ treated with breast-conserving therapy
Authors: Rakovitch E , Sutradhar R , Lalani N , Gu S , Nofech-Mozes S , Hanna W , Fong C , Paszat L 
Published: May 2019

Abstract
Purpose: Ductal Carcinoma in Situ (DCIS) with microinvasion (MI) (&lt; 1mm) includes a spectrum of cases with a single focus of MI and those with multiple foci (2 or more) of MI. The impact of multiple foci of MI on the risks of local recurrence (LR), invasive LR and breast cancer-specific survival (BCSS) is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment than those with a single focus of MI or pure DCIS. We examined the impact of multiple foci of MI, confirmed by expert pathology review, on the 15-yr risks of LR, invasive LR and breast-cancer specific survival (BCSS) in a population cohort of DCIS (+/-MI) treated with breast-conserving surgery (BCS) +/- radiotherapy (RT).
Methods: The cohort includes all women diagnosed with DCIS +/- MI in Ontario from 1994-2003 treated with BCS+/-RT. Cases with prior malignancy were excluded. Treatment and outcomes were ascertained by deterministic linkage with chart validation. Cause of death was determined from the provincial cancer registry or terminal hospital admission records. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of ipsilateral invasive LR and ipsilateral DCIS LR, adjusting for significant co-variates. The 15-yr invasive local recurrence-free survival (LRFS), DCIS LRFS and 15-yr BCSS risks were calculated using the Kaplan-Meier method with differences compared using the log-rank test.
Results: The cohort includes 3529 women; 2988 (85%) with pathology review are included in this analysis. 2,721 had pure DCIS (51% received RT), 267 had DCIS with MI (1 focus, N=156; multiple foci, N=111 (58% had RT)). Median follow-up was 13 years. Median age at diagnosis was 58 years. LR developed in 571 cases (21%) of pure DCIS, 33 cases (21%) with 1 focus of MI and 23 cases (27%) with multiple foci of MI. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR=1.59, 95%CI: 1.01-2.49, p=0.04) but not DCIS LR (HR=0.89, 95%CI: 0.46, 1.76, p=0.7). Women with multiple foci of MI had higher risks of invasive LR and lower BCSS at 15 years compared to those with pure DCIS. The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% for cases treated by BCS alone and 87.2%, 89.9% and 77% following BCS+RT without boost; however, women treated with boost RT had substantially higher 15-yr invasive LRFS risks than those who did not receive boost RT. The 15-yr invasive LRFS risks for those with pure DCIS, 1 or multiple foci of MI, were 89.2%, 91.3% and 95% (all p values&gt;.05, limited by low event rate). The 15-yr BCSS risks for cases with 1 focus, multiple foci of MI or pure DCIS were 92.1%, 93.1%, 96.4% (p=.006).
Conclusions: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR and lower breast-cancer specific survival after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.
Citation Format: Rakovitch E, Sutradhar R, Lalani N, Gu S, Nofech-Mozes S, Hanna W, Fong C, Paszat L. Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence and an increased risk of breast cancer mortality in women with ductal carcinoma in situ treated with breast-conserving therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-03.