Marc Ryser

<jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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)</jats:p> <jats:p>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.</jats:p>

<jats:p> 6516 </jats:p><jats:p> Background: Due to the elevated risk of ipsilateral invasive breast cancer (iIBC) after diagnosis with primary ductal carcinoma in situ (DCIS), professional guidelines recommend surveillance screening within 6-12 months (mo) after completion of initial local treatment and annually thereafter. To characterize adherence to these guidelines, we explored longitudinal patterns of utilization and factors associated with the use of surveillance imaging (mammography, MRI, ultrasound) for women with primary DCIS treated with breast conserving surgery (BCS) ± radiotherapy (RT) within 6 mo of diagnosis. Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-15 was selected from 1,330 Commission on Cancer-accredited facilities (up to 20/site) in the US. All imaging exams coded as asymptomatic were collected from 6 mo up to 10 years (yr) post-diagnosis. Time was defined according to 12-mo long surveillance periods. To be included in a given surveillance period, women had to be alive and free of a new breast cancer diagnosis through the end of the period. Women were classified as “consistent” screeners if they had at least one surveillance screen during each period, for the first 5 yr post-treatment or until censoring, whichever occurred first. Repeated measures multivariable logistic regression with generalized estimating equations was used to model receipt of surveillance breast imaging over time. The model included clinical and socioeconomic features. Results: The final analytic cohort contained 12,559 women; 8,989 (71.6%) received RT after BCS. Median age was 60 yr (interquartile range: 52-69) and median follow-up was 5.6 yr (95% confidence interval [CI] 5.6-5.7). Among women who received BCS (instead of BCS+RT), 62.5% (79.7%) underwent surveillance imaging within 6-18 mo after diagnosis. 38.7% (54.0%) were categorized as “consistent” screeners. Compared to white women, Black women were less likely to receive surveillance screening after treatment for primary DCIS (odds ratio [OR] 0.85, 95% CI 0.77-0.94). Hispanic ethnicity had a similar association (OR 0.86, 95% CI 0.74-0.99) compared to non-Hispanic ethnicity. Women with private insurance, compared to government insurance, were more likely to receive screening (OR 1.20, 95% CI 1.11-1.30). Prognostic tumor features indicative of a higher risk of subsequent iIBC, including higher grade, presence of comedonecrosis, and hormone receptor-negative DCIS, were not associated with screening uptake. Conclusions: Despite guidelines recommending annual surveillance imaging, many women with primary DCIS do not undergo regular imaging after BCS. The findings from this US-based study suggest that disparities in screening uptake are associated with race/ethnicity and insurance status rather than prognostic tumor features. </jats:p>

Most cancer types develop the ability to leave their site of origin and spread to distant organs to form metastases, also called secondary cancers. Metastases are the most common cause of death among cancer patients, and hence there is an immense clinical interest to understand the underlying biological mechanisms and to develop preventive and therapeutic measures. Over the past decades, an increasing number of applied mathematicians and biomedical engineers have taken on the challenge to design models and devise in silico tools for the study of cancer and cancer metastases. The goals of this chapter are to introduce to the reader the important challenges in the field of metastases and to give an overview of the existing modeling tools. Guided by pertinent biological questions, we review a number of deterministic and stochastic approaches and discuss their potential and limitations.