Background Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. Methods Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy’s Cancer Centre and King’s College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. Results Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15–3.38)], Asian ethnicity [3.42 (1. 59–7.35)], haematological cancer [2.03 (1.16–3.56)] and a cancer diagnosis for >2–5 years [2.81 (1.41–5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). Conclusions Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.

Invasive lobular breast cancer (ILC) accounts for 10–15% of breast cancers and has distinct characteristics compared with the more common invasive ductal carcinoma (IDC). Studies have shown that ILC may be less sensitive to chemotherapy than IDC, with lower rates of complete pathological response after neo-adjuvant chemotherapy, but it is not clear how this affects long-term survival. Patients at Guy’s and St Thomas’ NHS Foundation Trust between 1975 and 2016 diagnosed with ER+ IDC or ER+ ILC were eligible for inclusion. Kaplan–Meier plots and Cox proportional-hazards regression models were used for analysis. There was no difference in overall survival comparing ER+ ILC to ER+ IDC (OR: 0.94, 95% CI: 0.83, 1.04) with a median follow-up time of 8.3 years compared to 8.4 years in IDC. However, ER+HER2− ILC had worse survival compared to ER+HER2− IDC in those that received chemotherapy (OR: 1.46, 95% CI: 1.06, 2.01). Here, median follow-up time was 7.0 years in ILC compared to 8.1 years in IDC. These results indicate worse overall survival after chemotherapy (neo-adjuvant and adjuvant) in ILC compared to ER+HER2− IDC even when correcting for tumour grade, age, size, and nodal involvement, but validation is needed in a larger study population.

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Background: Although DCIS is a precursor of invasive breast cancer (IBC), most DCIS lesions never will progress. As we cannot distinguish reliably progressive from harmless DCIS yet, almost all women with DCIS are treated extensively with surgery and often adjuvant radiotherapy or endocrine treatment, implying overtreatment of many thousands of women with harmless DCIS. PRECISION aims to reduce such overtreatment by identifying factors associated with subsequent ipsilateral IBC. Many factors have been implicated in subsequent DCIS and IBC risk, but most studies relied on small series with limited prognostic power. To overcome this, we conducted pooled analyses of four large cohorts with DCIS from three different countries. Methods: Cohorts were pooled with data of 48,804 women with DCIS: a population-based cohort (NL, n=18,996), prospective, a population-based, screening cohort (Sloane, UK, n=8,462), a single center cohort (MDACC, USA, n=2,363), and a representative DCIS patient series from the National Cancer Database Special Study (USA, n=18,983). Patients with missing data on treatment and follow-up or follow-up shorter than six months were excluded from analyses. Risk of a subsequent ipsilateral invasive breast cancer (iIBC) was assessed in three DCIS lesion size groups (&lt;20mm, 20-50mm and ≥50mm) and in patients who had clear surgical margins (&lt;2mm) after final breast conserving surgery (BCS) versus patients who did not. Cox proportional hazards models were used to assess differences in risk of IBC, with a focus on DCIS size and margin status. Results: In final analyses, 48,576 patients, diagnosed between 1999 and 2017, were included. Median follow-up was 7.6 years (range 0.5-21.1). In multivariable analyses, patients with smaller size of DCIS (&lt;20mm) had a decreased risk of iIBC compared with women with larger lesion size (HR 0.81; 95% CI 0.68-0.97). In 33,091 BCS treated patients, patients with clear surgical margins had a decreased risk of iIBC (HR 0.68; 95% CI 0.52-0.90). Conclusion: In our quest to reduce overtreatment for women with DCIS, we have identified free surgical margins and smaller lesion size as independent factors reducing the risk of subsequent ipsilateral invasive breast cancer, irrespective of the treatment received. Knowledge of these, and additional, factors could aid in selecting patients suitable for less invasive management strategies such as active surveillance or omitting radiotherapy. This work was supported by Cancer Research UK and by KWF Dutch Cancer Society (ref.C38317/A24043); Web site: https://cancergrandchallenges.org/teams/precision Citation Format: Renee S. Schmitz, Alexandra W. van den Belt-Dusebout, Karen Clements, Yi Ren, Chiara Cresta, Jasmine Timbres, Yat-Hee Liu, Danalyn Byng, Thomas Lynch, Brian Menegaz, Deborah Collyar, Terry Hyslop, Michael Schaapveld, Elinor Sawyer, Shelley E. Hwang, Alastair Thompson, Marc D. Ryser, Jelle Wesseling, Esther H. Lips, Marjanka K. Schmidt, Grand Challenge PRECISION Consortium. Subsequent invasive breast cancer risk after DCIS treatment in multinational PRECISION consortium cohorts comprising 48,576 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 686.

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.