Long-term risk of subsequent ipsilateral lesions after surgery with or without radiotherapy for ductal carcinoma in situ of the breast

Alastair Thompson,Michael Schaapveld,Esther H. Lips,Linda de Munck,Marjanka K. Schmidt,Paula H. M. Elkhuizen,Elinor Sawyer,Daniele Giardiello,Jelle Wesseling,Marc D. Ryser,E. Shelley Hwang,Liping Fu,Frederieke van Duijnhoven,Lotte E. Elshof,Maartje van Seijen

doi:10.1038/s41416-021-01496-6

Abstract

BackgroundRadiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort.MethodsThe cohort comprised all women diagnosed with DCIS in the Netherlands during 1989–2004 with follow-up until 2017. Cumulative incidence of iDCIS and iIBC following BCS and BCS + RT were assessed. Associations of DCIS treatment with iDCIS and iIBC risk were estimated in multivariable Cox models.ResultsThe 20-year cumulative incidence of any ipsilateral breast event was 30.6% (95% confidence interval (CI): 28.9–32.6) after BCS compared to 18.2% (95% CI 16.3–20.3) following BCS + RT. Women treated with BCS compared to BCS + RT had higher risk of developing iDCIS and iIBC within 5 years after DCIS diagnosis (for iDCIS: hazard ratio (HR)age < 50 3.2 (95% CI 1.6–6.6); HRage ≥ 50 3.6 (95% CI 2.6–4.8) and for iIBC: HRage<50 2.1 (95% CI 1.4–3.2); HRage ≥ 50 4.3 (95% CI 3.0–6.0)). After 10 years, the risk of iDCIS and iIBC no longer differed for BCS versus BCS + RT (for iDCIS: HRage < 50 0.7 (95% CI 0.3–1.5); HRage ≥ 50 0.7 (95% CI 0.4–1.3) and for iIBC: HRage < 50 0.6 (95% CI 0.4–0.9); HRage ≥ 50 1.2 (95% CI 0.9–1.6)).ConclusionRT is associated with lower iDCIS and iIBC risk up to 10 years after BCS, but this effect wanes thereafter.

Highlights

Since the introduction of population-based mammography breast cancer screening in the 1990s, ductal carcinoma in situ (DCIS) comprises ~15% of all newly diagnosed neoplastic breast lesions [1, 2]
Women treated with breastconserving surgery (BCS) compared to BCS + RT had higher risk of developing ipsilateral DCIS (iDCIS) and ipsilateral IBC (iIBC) within 5 years after DCIS diagnosis (for iDCIS: hazard ratio (HR)age < 50 3.2; HRage ≥ 50 3.6 and for iIBC: HRage
After 10 years, the risk of iDCIS and iIBC no longer differed for BCS versus BCS + RT (for iDCIS: HRage < 50 0.7; HRage ≥ 50 0.7 and for iIBC: HRage < 50 0.6; HRage ≥ 50 1.2)

Summary

Introduction

Since the introduction of population-based mammography breast cancer screening in the 1990s, ductal carcinoma in situ (DCIS) comprises ~15% of all newly diagnosed neoplastic breast lesions [1, 2]. RT as an adjunct to BCS as a treatment for DCIS was evaluated in several clinical trials (NSABP B17, EORTC 10853, SweDCIS, UK/ANZ), and a meta-analysis demonstrated a 15% absolute 10-year risk reduction of both subsequent ipsilateral DCIS (iDCIS) and ipsilateral IBC (iIBC) lesions for BCS + RT versus BCS only, without effect on breast cancer-specific survival and overall survival [5,6,7,8,9] How these trial data translate into a reduction of ipsilateral breast events in large, population-based patient cohorts in the longer term is unclear. CONCLUSION: RT is associated with lower iDCIS and iIBC risk up to 10 years after BCS, but this effect wanes thereafter

Methods

Results

Conclusion