Abstract P1-22-06: A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme
Authors: Clements Karen , Maxwell Anthony , Hilton Bridget , Wallis Matthew , Kirwan Cliona , Stobart Hilary , Provenzano Elena , Sharma Nisha , Litherland Janet , Shaaban Abeer , Dodwell David , Dulson-Cox Joanne , Sawyer Elinor , Mylvaganam Senthurun , Kearins Olive , Brace-McDonnell Samantha , Pinder Sarah , Thompson Alastair 
Published: March 2022

Abstract
Background The variable natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this retrospective cohort study was to determine the outcomes of women who were diagnosed through the English National Health Service Breast Screening Programme (NHS BSP) and had no surgery for screen-detected DCIS. Method English NHS BSP databases were searched for women diagnosed with DCIS without invasive cancer on needle biopsy between 1 April 2001 and 31 March 2018 inclusive, who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data for further treatment, event information and mortality records. Details of potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment, subsequent clinical course and outcomes. Results Data for 311 eligible women (median age 62 years) were included, with median follow-up (primary DCIS diagnosis to either surgery, development of invasive disease, death or last known to be alive) of 4.1 years (range 0.5 to 17.4 years). The median age at diagnosis was 64 years (range 47 to 90 years). Sixty (19%) women developed invasive breast cancer, 56 ipsilateral and 4 contralateral. Twenty-two women (7%) underwent surgery for DCIS (&gt;6 months after diagnosis) and 86 (28%) died of other causes. Women with high or intermediate grade DCIS were significantly more likely to develop ipsilateral invasive breast cancer (iIBC) than those with low grade DCIS. 28/123 (23%) with high grade DCIS, 21/105 (20%) with intermediate grade DCIS, 5/76 (7%) with low grade DCIS and 2/7 (29%) with an unknown grade of DCIS developed iIBC. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. Women who developed iIBC were significantly younger than those who did not. This was driven primarily by a strong association among those with high grade DCIS. There was no significant difference in age between those with intermediate and low grade DCIS respectively who did or did not develop iIBC. The median baseline size of DCIS in women who developed iIBC was higher than in women who did not develop iIBC, both overall and in each of the three grade categories (median sizes - high grade 38 mm vs 29 mm, p=0.19; intermediate grade 35 mm vs 18 mm, p=0.31; low grade 18 mm vs 15 mm, p=0.38). This reached statistical significance for all grades combined: 37 mm (range 3-95) v 20 mm (range 3-200), p=0.02. Of the 262 women with a known microinvasion status, 8/25 (32%) with definite or possible microinvasion were subsequently diagnosed with ipsilateral invasive cancer compared to 38/237 (16%) without microinvasion (p=0.027). There was no significant association on univariable analysis between risk of iIBC and microcalcification as the predominant radiological feature (iIBC and microcalcification 47/258 vs iIBC and other radiological feature 7/46; p=0.83), the presence of histological necrosis (iIBC and necrosis, 14/89 vs iIBC and no necrosis, 31/157; p=0.49) or the use of ET (iIBC and ET 11/67 vs iIBC and no ET 45/244; p=0.86). Of the 51 invasive cancers that developed with a known grade, 46 (90%) were grade 2 or 3. Conclusion The findings suggest that women diagnosed with high or intermediate grade DCIS and those with microinvasion should continue to be offered surgery. For those with low grade DCIS there is a need for shared decision-making in the choice of surgery or active surveillance based on a discussion of the risks and benefits of the options as currently understood, and in the light of the low reproducibility of DCIS grading.
Citation Format: Karen Clements, Anthony Maxwell, Bridget Hilton, Matthew Wallis, Cliona Kirwan, Hilary Stobart, Elena Provenzano, Nisha Sharma, Janet Litherland, Abeer Shaaban, David Dodwell, Joanne Dulson-Cox, Elinor Sawyer, Senthurun Mylvaganam, Olive Kearins, Samantha Brace-McDonnell, Sarah Pinder, Alastair Thompson. A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-06.