Abstract P1-22-02: Subsequent risk of ipsilateral breast events in a multinational DCIS cohort of 48.619 patients: A meta-analysis within the PRECISION consortium
Authors: Schmitz Renée SJM , van den Belt-Dusebout Sandra W , Cresta Chiara , Liu Yat-Hee , Schaapveld Michael , Clements Karen , Timbres Jasmine , Byng Danalyn T , Ryser Marc D , Ren Yi , Lynch Thomas , Hyslop Terry , Menegaz Brian , Collyar Deborah , Hwang Shelley , Thompson Alastair , Sawyer Elinor , Wesseling Jelle , Lips Esther H , Schmidt Marjanka K ,   Grand Challenge PRECISION consortium
Published: March 2022

Background: The PRECISION (PREvent ductal Carcinoma In Situ Invasive Overtreatment Now) CRUK Grand Challenge project focusses on discriminating hazardous from indolent ductal carcinoma in situ (DCIS). Aim of these analyses is to identify factors associated with a lower or higher risk of developing invasive breast cancer after an initial DCIS diagnosis. Knowledge of these factors is crucial in our quest to reducing overtreatment for women with DCIS. Many clinicopathological features are hypothesized to be important factors affecting the risk of a subsequent breast lesion. Most studies performed so far are from trial or single country studies, we now present an integrated analysis of four different cohorts from three countries.Methods: Four cohorts from the three countries participating in PRECISION were identified. A population based cohort from the Netherlands cancer registry (Dutch cohort); a population based, prospective, screening cohort from the United Kingdom (Sloane cohort); a single center cohort from MD Anderson Cancer Center (MDACC) and a subset of DCIS patients abstracted from a population based National Cancer Database Special Study cohort (NCDB subset) in the United States. Patient-level data from these cohorts were combined for this analysis. Subsequent ipsilateral invasive breast cancer (iIBC) and subsequent ipsilateral DCIS (iDCIS) were assessed at five and ten years by Kaplan Meier analysis. The cumulative incidence of iIBC was assessed in three treatment groups: breast conserving surgery only (BCS), breast conserving surgery with radiotherapy (BCS+RT) and mastectomy (MST). Cumulative incidence of iDCIS was assessed in patients receiving BCS or BCS+RT. Additionally, cumulative incidences were calculated for iIBC and IDCIS in patients who received endocrine treatment (ET) after BCS or BCS+RT versus patients who did not receive ET. All cumulative incidences were calculated with death as competing risk. Results: The joint PRECISION cohort consisted of 48,619 patients, diagnosed between 1999 and 2017. Median follow-up was 7.4 years (0.6-17.9). In preliminary analyses, Kaplan Meier curves showed broadly similar risks in iIBC and iDCIS between the four different cohorts. The cumulative incidence of iIBC was 1.6% at five years and 3.5% at 10 years. Five-year cumulative incidence of iIBC was highest in patients receiving BCS (3.4%) compared with patients receiving BCS+RT or MST (1.3%). The cumulative incidence of iDCIS was 1.7% at 5 years and 2.4% at 10 years. Five-year cumulative incidence of iDCIS was higher in patients receiving BCS (3.5%) compared to patients receiving BCS+RT (1.9%). In univariate analyses, the effect of ET on cumulative incidence of both iIBC and iDCIS was modest, especially with respect to radiotherapy. Conclusion: Overall, 5- and 10-year incidence of an ipsilateral in situ or invasive breast lesion was low and similar between the four different cohorts. The incidence of iIBC and iDCIS was higher in patients receiving BCS, compared to women receiving BCS+RT or MST.

Table 1.Cohort and patient characteristicsDutch Cohort Sloane MDACCNCDB subsetTotal CohortN=18,995N=8,425N=1,820N=19,379N=48,619Cohort descriptionProspectiveNoYesNoNoPopulation basedYesYesNo, single centerYesScreening and non-screeningYesScreening onlyYesYesMean (min - max)Mean (min - max)Mean (min - max)Mean (min-max)Mean (min-max)Age diagnosis DCIS58.3 (21-94)59.8 (46-88)55.6 (20-90)59.7 (20-98)59.0 (20-98)Year of diagnosis (range)1999-20152003-20121999-20172007-20151999-2017Follow-up in years10.4 (0.5-21.1)5.3 (0.5-9.7)8.7 (0.25-17.8)5.8 (0.5-10.7)7.6 (0.25-2.1)N (%)N (%)N (%)N (%)N (%)GradeGrade 12,844 (15.0)784 (9.3)141 (7.8)3,158 (16.3)6,927 (14.3)Grade 25,952 (31.3)2,328 (27.6)737 (40.5)6,844 (35.3)15,861 (32.6)Grade 38,944 (47.1)5,305 (62.9)933 (51.3)7,848 (40.5)23,030 (47.3)Unknown grade1,255 (6.6)8 (0.1)9 (0.5)1,529 (7.9)2,801 (5.8)Type of surgeryBreast conserving surgery (BCS)11,790 (62.1)5,830 (69.2)1,031 (56.7)14,504 (74.8)33,155 (68.2)Mastectomy (MST)7,205 (37.9)2,595 (30.8)789 (43.4)4,875 (25.2)15,464 (31.8)Adjuvant treatmentRadiotherapy (RT)9,650 (50.8)3,418 (40.6)762 (41.9)10,620 (54.8)24,450 (50.3)Endocrine treatmentNA1,151 (13.6)999 (54.9)8,849 (45.7)10,999 (37.0)5 years Cumulative IncidencesiIBC1.4%2.3%1.6%1.7%1.6%iDCIS1.5%2.0%1.6%1.7%1.7%Vital statusAlive16,472 (86.7)8,147 (96.7)1,668 (91.7)18,161 (93.7)44,448 (91.4)Deceased2,523 (13.3)278 (3.3)152 (8.4)1,218 (6.3)4,171 (8.6)This work was supported by Cancer Research UK and by KWF Dutch Cancer Society (ref.C38317/A24043)

Citation Format: Renée SJM Schmitz, Sandra W van den Belt-Dusebout, Chiara Cresta, Yat-Hee Liu, Michael Schaapveld, Karen Clements, Jasmine Timbres, Danalyn T Byng, Marc D Ryser, Yi Ren, Thomas Lynch, Terry Hyslop, Brian Menegaz, Deborah Collyar, Shelley Hwang, Alastair Thompson, Elinor Sawyer, Jelle Wesseling, Esther H Lips, Marjanka K Schmidt, Grand Challenge PRECISION consortium. Subsequent risk of ipsilateral breast events in a multinational DCIS cohort of 48.619 patients: A meta-analysis within the PRECISION consortium [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 P1-22-02.