Abstract P4-15-04: A longitudinal cohort study to identify risk factors for the development of invasive cancer in unresected DCIS
Authors: Maxwell AJ , Clements K , Hilton B , Dodwell DJ , Evans A , Olive K , Pinder SE , Thomas J , Matthew WG , Thompson AM 
Published: February 2018

Abstract
Background: The variable natural history of ductal carcinoma in situ (DCIS) remains poorly understood. Randomized trials of active surveillance versus guideline concordant care are currently underway: the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial in the US, LOw Risk dcIS (LORIS) trial in the UK and Low Risk Dcis (LORD) in Europe. Given this context, we examined the outcomes of a contemporary group of women with DCIS who did not undergo initial surgical resection.
Methods: A longitudinal cohort of women diagnosed with DCIS on needle biopsy who did not undergo initial surgical excision for ≥1 year were identified through the Cancer Registry with case note and death certificate review for subsequent outcomes.
Results: Eighty-nine eligible women with DCIS alone diagnosed on needle biopsy (most with 14-gauge core needle biopsy) between 1998 and 2010 were identified. The mean age at diagnosis was 72 years (range 44-94 years) with mean follow-up (diagnosis to death, invasive disease or last review) of 62 months (range 12-180 months). Twenty-nine women (33%) developed histologically proven invasive breast cancer, 28 at the site of the initial DCIS biopsy, after a mean interval of 54 months (range 12-144 months): 14/29 (48%) women originally had high grade DCIS, 10/31 (32%) intermediate grade and 3/17 (18%) low grade DCIS (initial grade not known in 12). Time to detect a diagnosis of invasive breast cancer was associated with initial grade of DCIS (p=0.0016, log-rank test): after mean intervals of 41 months (high grade), 69 months (intermediate grade) and 78 months (low grade) respectively. Younger age was associated with development of invasive disease (p&lt;0.003, Mann-Whitney U-Test). High grade (grade 3) invasive breast cancer exclusively occurred in women with a prior diagnosis of high grade DCIS. Invasion was more frequent in lesions with calcification as the predominant feature than those without (23/50 v. 5/25; p&lt;0.05, Fisher exact test). Forty-four women were prescribed endocrine therapy, use of which was associated with a lower rate of invasive breast cancer (p&lt;0.05). Ultimately 18 women underwent surgery, 17 for invasive cancer. The mean interval from DCIS diagnosis to death was 76 months for those who developed invasive cancer; 48/89 women died, 12 had a certified cause of death as breast cancer.
Conclusion: High grade DCIS, mammographic microcalcification and lack of endocrine therapy were associated with progression to invasion. The findings suggest surgical excision of high grade DCIS should continue but provides support that women with DCIS features which include low grade should be considered for the COMET, LORIS or LORD active surveillance trials.
Citation Format: Maxwell AJ, Clements K, Hilton B, Dodwell DJ, Evans A, Olive K, Pinder SE, Thomas J, Matthew WG, Thompson AM. A longitudinal cohort study to identify risk factors for the development of invasive cancer in unresected DCIS [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 P4-15-04.