Work

Prognostic Risk Assessment and Prediction of Radiotherapy Benefit for Women with Ductal Carcinoma In Situ (DCIS) of the Breast, in a Randomized Clinical Trial (SweDCIS)

Year: 2021

Type: article

Abstract: Background: Risk assessment and prediction of radiotherapy (RT) benefit after breast conserving surgery (BCS) for DCIS are crucial. The study aim was to validate DCISionRT ® in a large randomized cohort (SweDCIS) with long term followup. Methods: Women were randomised to RT or control after BCS, between 1988 and 2000. Tumour blocks were collected and slides were sent to PreludeDx, and DCISionRT test results were reported. Associations between the continuous decision score (DS) and 10–year ipsilateral recurrences, comprising invasive breast events (InvBE) and total (DCIS+InvBE) breast events (TotBE), in women treated without RT, and RT effect on rates within Low (DS≤3) and Elevated Risk (DS>3) groups were assessed independently in Sweden and verified. Findings: In 504 women with complete biosignature data and negative margins, DCISionRT divided women into Elevated (52%) and Low Risk (48%) groups. In the Elevated Risk group, RT decreased 10-year relative TotBE and InvBE rates, HR 0·32 (0·17–0·58) and HR 0·24 (0·08–0·74), with corresponding absolute decreases in TotBE and InvBE rates of 15·5% (95%CI 5·9–25·0%) and 9·3%(2·0–16·5%). In the Low Risk group, the relative RT benefit was lower: HR 0·53 (0·28–1·02) and 0·84 (0·30–2·31), with absolute differences with RT of 5·7%(-0·8–12·2%) and 1·2%(-5·7–8·2%). Recurrences at 10-years without RT, increased with increasing DS, HRs per 5 DS-units for TotBE and InvBE were 1·5(1·1–2·3) and 1·5(0·7–2·8). Interpretation: Our data support that DCISionRT showed prognostic and predictive value, identifying women with elevated recurrence risk who benefited substantially from RT after BCS. In addition, the test identified women with low absolute risk, and minor absolute risk differences from RT. Absolute 10-year recurrence risks in the DS Low and Elevated Risk groups with and without RT are sufficiently different to indicate that DCISionRT can inform selection of individual adjuvant DCIS treatment strategy. Funding: NCI Grant ID:1R44CA162744 supported PreludeDx. Declaration of Interest: FW reports funding from PreludeDx to Uppsala University for tumour tissue processing and collaborative inventorship with PreludeDx on biomarkers for DCIS risk assessment. PK and EH each report a research contract with PreludeDx for the current study, and collaborative inventorship pertaining to invasive breast cancer outside the scope of this manuscript in conjunction with PreludeDx and KHS BiomedInvent AB, as well as stock or stock options for KHS BiomedInvent AB. PW is a co-owner of TME, LLC, which provides advisory services to PreludeDx and other medical device companies and received funding outside of the scope of this manuscript. JS has stock options and is a consulting Pathologist for PreludeDx providing pathology services. TSB is an inventor and receives royalty income for “Use of ZAP-70 for prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),” which is outside of the scope of this manuscript. GL has stock options with PreludeDx. SL was the PI of NIH SBIR Fast-Track Grant 1R44CA162744 to analyze patient samples and data from the SweDCIS study sites, and owns 200 shares of stock in PreludeDx. SS is an employee of and has stock options with PreludeDx. FV is a consultant for Impedimed and a research advisor for PreludeDx. CS has a clinical research grant and is a consultant for PreludeDx, as well as ViosionRT, Varian, Impedimed and Evicore. SW has received research grant funding from PreludeDx for research outside of the scope of this manuscript, but otherwise declares no competing interests for this manuscript. TB is the Chief Scientific Officer of and owns stock in PreludeDx and holds patents for the DCISionRT test. KS, and BM declare no competing interests. Ethical Approval: This study was approved by the ethics committee at Umeå University, Sweden, Dnr 2005:118, with amendments 2005/118/02 and 2014-230-32M.

Source: Cancers

DOI: 10.3390/cancers13236103