Abstract P4-15-07: Quantifying the natural history and overtreatment rate of ductal carcinoma in situ
Authors: Ryser MD , Weaver DL , Marks JR , Hyslop T , Hwang ES 
Published: February 2018

Abstract
Background. Subsets of ductal carcinoma in situ (DCIS) are thought to be relatively indolent disease with long progression time to invasive cancer. Nevertheless, the vast majority of women diagnosed with DCIS undergo extirpative surgery, potentially leading to widespread overtreatment of patients who would not develop symptomatic breast cancer in absence of treatment. Due to a poor understanding of the natural history of untreated DCIS, it remains difficult to derive estimates of the true rate of overtreatment. The objective of this study was to quantify the natural history of untreated DCIS through synthesis of retrospective data sources and to estimate the associated rate of overtreatment.
Methods. A systematic PubMed search was performed to identify published studies on ipsilateral invasive cancer-free survival in women who did not undergo surgery with curative intent after diagnosis with DCIS. Individual life histories from included studies were manually extracted and aggregated in a patient-level meta-analysis. Each lesion was assigned to one of three categories: DCIS precursor lesions, low-risk DCIS, and high-risk DCIS. Time-to-event analyses (Kaplan-Meier) and Cox proportional-hazards models were used to calculate absolute and relative progression rates for the three risk groups. For the low-risk group, overtreatment rates were estimated by means of a competing risk analysis. For this purpose, progression hazards were estimated by maximum likelihood inference of parametric mixture models, and non-breast cancer mortality rates were derived from standardized life tables (birth cohort: 1960).
Results. A total of n=122 women from 3 retrospective studies were included in the patient-level meta-analysis. The median age at diagnosis was 47 years (interquartile range [IQR]: 41-57) and median follow-up was 17 years (IQR: 6-20). Compared to DCIS precursor lesions (n=38), relative rates of progression to invasive cancer were significantly higher for both low-risk DCIS (n=68; hazard ratio [HR]: 4.8, 95%-CI: 1.4-16.0) and high-risk DCIS (n=16; HR: 6.9, 95%-CI: 1.7-27.8). Among women with low-risk DCIS, the cumulative progression to ipsilateral invasive disease after 5, 10, and 20 years was found to be 16.9% (95%-CI: 9.7-28.5), 28.5% (95%-CI: 16.6-38.8) and 35.1% (95%-CI: 23.8-49.8), respectively. The corresponding overtreatment rates for low-risk DCIS were estimated to be of the order of 56%, 63% and 72% for ages at diagnosis of 55, 65 and 75 years respectively.
Conclusion. To our knowledge, this study constitutes the most comprehensive quantitative analysis of the natural history of incompletely treated DCIS. The estimated propensity to progress to invasive disease suggests overtreatment among some women diagnosed with low-risk DCIS, especially in older patients with comorbidities. The extent to which this cohort resembles those currently diagnosed with DCIS is unclear. However, these results underscore the importance of clinical trials in evaluating active surveillance and/or anti-estrogen therapy as alternative management strategies for women diagnosed with low-risk DCIS.
Citation Format: Ryser MD, Weaver DL, Marks JR, Hyslop T, Hwang ES. Quantifying the natural history and overtreatment rate of ductal carcinoma in situ [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 P4-15-07.