Abstract P4-15-13: When is cancer not really cancer? The PREvent ductal carcinoma in situ invasive overtreatment now (PRECISION)* initiative

Abstract

Abstract Background Ductal carcinoma in situ (DCIS) now represents 20-25% of all breast neoplasia due to large-scale detection by widely adopted population-based breast cancer screening programs. As a result, thousands of women are confronted with DCIS each year: more than 8,000 in the UK, 2,500 in the Netherlands, and some 50,000 in the US. Conventional management includes surgery, supplemented by radiotherapy and/or endocrine therapy, but overtreats the majority of DCIS as ˜1% recur annually and breast cancer mortality is ˜3% at 20 years. Uncertainty as to which DCIS lesions will progress to invasive cancer or, after excision, which will return with recurrent DCIS or invasive breast 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 may be best achieved by synergistic international collaboration between leading global experts from various disciplines, driven by the essential input from patient voices as full members of the research team. 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: Wesseling J, Thompson A, Nik-Zainal S, Futreal A, Hwang S, Jonkers J, Lips E, Rea D, On Behalf of the PRECISION Team. When is cancer not really cancer? The PREvent ductal carcinoma in situ invasive overtreatment now (PRECISION)* initiative [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-13.