Abstract 686: Subsequent invasive breast cancer risk after DCIS treatment in multinational PRECISION consortium cohorts comprising 48,576 patients

Abstract

Background: Although DCIS is a precursor of invasive breast cancer (IBC), most DCIS lesions never will progress. As we cannot distinguish reliably progressive from harmless DCIS yet, almost all women with DCIS are treated extensively with surgery and often adjuvant radiotherapy or endocrine treatment, implying overtreatment of many thousands of women with harmless DCIS. PRECISION aims to reduce such overtreatment by identifying factors associated with subsequent ipsilateral IBC. Many factors have been implicated in subsequent DCIS and IBC risk, but most studies relied on small series with limited prognostic power. To overcome this, we conducted pooled analyses of four large cohorts with DCIS from three different countries. Methods: Cohorts were pooled with data of 48,804 women with DCIS: a population-based cohort (NL, n=18,996), prospective, a population-based, screening cohort (Sloane, UK, n=8,462), a single center cohort (MDACC, USA, n=2,363), and a representative DCIS patient series from the National Cancer Database Special Study (USA, n=18,983). Patients with missing data on treatment and follow-up or follow-up shorter than six months were excluded from analyses. Risk of a subsequent ipsilateral invasive breast cancer (iIBC) was assessed in three DCIS lesion size groups (<20mm, 20-50mm and ≥50mm) and in patients who had clear surgical margins (<2mm) after final breast conserving surgery (BCS) versus patients who did not. Cox proportional hazards models were used to assess differences in risk of IBC, with a focus on DCIS size and margin status. Results: In final analyses, 48,576 patients, diagnosed between 1999 and 2017, were included. Median follow-up was 7.6 years (range 0.5-21.1). In multivariable analyses, patients with smaller size of DCIS (<20mm) had a decreased risk of iIBC compared with women with larger lesion size (HR 0.81; 95% CI 0.68-0.97). In 33,091 BCS treated patients, patients with clear surgical margins had a decreased risk of iIBC (HR 0.68; 95% CI 0.52-0.90). Conclusion: In our quest to reduce overtreatment for women with DCIS, we have identified free surgical margins and smaller lesion size as independent factors reducing the risk of subsequent ipsilateral invasive breast cancer, irrespective of the treatment received. Knowledge of these, and additional, factors could aid in selecting patients suitable for less invasive management strategies such as active surveillance or omitting radiotherapy. This work was supported by Cancer Research UK and by KWF Dutch Cancer Society (ref.C38317/A24043); Web site: https://cancergrandchallenges.org/teams/precision Citation Format: Renee S. Schmitz, Alexandra W. van den Belt-Dusebout, Karen Clements, Yi Ren, Chiara Cresta, Jasmine Timbres, Yat-Hee Liu, Danalyn Byng, Thomas Lynch, Brian Menegaz, Deborah Collyar, Terry Hyslop, Michael Schaapveld, Elinor Sawyer, Shelley E. Hwang, Alastair Thompson, Marc D. Ryser, Jelle Wesseling, Esther H. Lips, Marjanka K. Schmidt, Grand Challenge PRECISION Consortium. Subsequent invasive breast cancer risk after DCIS treatment in multinational PRECISION consortium cohorts comprising 48,576 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 686.