Background. Ductal carcinoma in situ (DCIS) represents 25% of all breast neoplasia due to population-based breast cancer screening. As a result, thousands of women are confronted with DCIS each year. Conventional management includes surgery, supplemented by radiotherapy and/or endocrine therapy, but overtreats the majority of DCIS. Uncertainty as to which DCIS lesions will progress to invasive cancer drives this overtreatment. This urges us to learn how to distinguish DCIS that may progress to invasive breast cancer from the majority of indolent DCIS. Such distinction is best achieved by synergistic collaboration between leading global experts from various disciplines, driven by the essential input from patient voices.

Aim. PRECISION (PREvent ductal Carcinoma In Situ Invasive Overtreatment Now) aims to save thousands of women with low risk DCIS the burden of intensive inappropriate treatment of DCIS (surgery, radiation therapy, hormonal therapies) through the discovery of new data and development of novel tests that promote informed and shared decision-making between patients and clinicians, without compromising the excellent outcomes for DCIS management presently achieved.

Methods. First, three large DCIS cohorts and supplementary resources will be collected enabling in depth molecular studies. Second, extensive genomic characterization, immune profiling and imaging analysis will be performed. In vivo and in vitro modeling will be performed to study the biology of DCIS in detail. Finally, all clinical, immune, and molecular data will be incorporated into a clinical risk prediction model. This risk prediction model will be validated in three prospective randomized DCIS trials in the US (COMET trial), UK (LORIS trial), and mainland Europe (LORD trial).

How the results of this research will be used. The discoveries from our laboratory studies, including a risk stratification model, will be cross-validated in three prospective trials of DCIS active surveillance versus conventional treatment (the COMET, LORIS, and LORD trials). As such, the main result of this study will be that we can identify a group of women for which active surveillance for DCIS could be a safer alternative to intensive treatment. Ultimately, this may also contribute to a more reassuring perception of risk regarding non-life threatening precancerous lesions in general, reducing anxiety and preserving quality of life.

* The PRECISION Team is a Cancer Research UK Grand Challenge Award 2017 winning team and will be jointly funded by Cancer Research UK and the Dutch Cancer Society

Citation Format: Jelle Wesseling, Alastair M. Thompson, Serena Nik-Zainal, Andrew Futreal, Shelley Hwang, Jos Jonkers, Esther H. Lips, Daniel Rea. When is cancer not really cancer: The PREvent Ductal Carcinoma In Situ Invasive Overtreatment Now (PRECISION)* initiative [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3259.