TEST:

Oncotype DX Breast DCIS Score test

No abstract available

Models incorporating the DS or RS more accurately predicted the 10-year risk of LR and invasive LR after BCS compared with models on the basis of CPF alone. Inclusion of the RS, compared with DS, did not improve the prediction of the 10-year risk of invasive LR.

Conclusion Using large unbiased samples series, we successfully build and validated an RNAseq classifier to predict invasive breast cancer risk after DCIS. This RNAseq predictor could change clinical practice by allowing clinicians to identify a subgroup of low-risk DCIS suitable for treatment de-escalation and studies of active surveillance.

Inclusion of the 21-Gene RS with CPF did not improve the prediction of the 10-year risk of LR or invasive LR. This suggests that nomograms that include the 12-Gene assay with CPF provide more accurate individualized estimates of recurrence risk after BCS and can help improve personalized decision-making in the management of DCIS.

Clinical applications of radiomic phenotypes may improve risk stratification and potentially result in decreased overtreatment of women diagnosed with DCIS. Table 1: Association between radiomic phenotypes and DCIS outcomes using a Chi square test.

P2b; The median 4-hydroxytamoxifen concentrations deep in the breast were nonsignificantly higher in the oral tamoxifen group (5.7 [IQR, 4.0-7.9] vs 3.8 [IQR, 1.3-7.9] ng/g), whereas endoxifen was abundant in the oral tamoxifen group and minimal in the 4-hydroxytamoxifen gel group (median, 13.0 [IQR, 8.9-20.6] vs 0.3 [IQR, 0-0.3] ng/g; P < .001). New transdermal approaches must deliver higher drug quantities and/or include the most potent metabolites. ClinicalTrials.gov Identifier: NCT02993159.

At the dose and duration used, anti-proliferative non-inferiority of 4OHT-gel to oral-TAM was not confirmed, potentially explained by endoxifen exposure differences. New transdermal approaches must deliver higher drug quantities and/or include all potent metabolites.

To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one-the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial-incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.

P=N/A; Recruiting --> Active, not recruiting

This trial suggests advanced quantitative MRI features may help identify DCIS lesions at risk for upstaging to invasive disease and IBR. Specifically, an imaging feature of vascular permeability (Ktrans) showed an expected positive association with upstaging. Imaging features of vascular permeability (Ktrans and ve) showed counterintuitive inverse associations with DCIS Scores.

DCIS risk models have poor agreement for determining IBR risk. DCIS Score Category initially identified many low-risk lesions; however, inclusion of clinical features to create a Refined Score decreased this substantially, providing very few additional low-risk cases for de-escalation over VNPI or MSK-N. Additional studies are needed to determine precise IBR rates when these models are used for adjuvant therapy decision-making.

The risk prediction of molecular signatures is independent of other risk stratification tools developed in DCIS, and have a tendency toward RT de-escalation. Further studies are needed to assess the impact on mortality.

P=N/A; Trial completion date: Dec 2022 --> Jun 2023

No abstracts available

Secondary endpoints included the 12-gene DCIS Score assay (Exact Sciences), breast tissue and plasma concentrations of 4-OHT and endoxifen, TAM-responsive circulating proteins, and patient reported symptoms (Breast Eight Symptom Scale). We estimated that 80 evaluable participants would provide 80.5% power to establish non-inferiority of 4-OHT, defined as relative Ki67-LI decline >35% and absolute decline >2.6%, with one-sided

Our analyses identified a subset of 5 miRNAs able to discriminate between Oncotype DX® DCIS score subgroups. Together, our data suggest that miRNA expression analysis may add value to the predictive and prognostic evaluation of DCIS lesions.

Interestingly, VMRs were enriched in cell adhesion pathways Conclusion The recently acquired knowledge described above on how often the subsequent IBC is directly related to the initial DCIS and on molecular markers predicting the risk of DCIS progression is essential for accurate DCIS risk assessment. This is essential to aid accurate clinical decision making to personalize DCIS management in the near future.

Tamoxifen and aromatase inhibitors have been proven to reduce the risk of recurrence by about 30-50%, and their use should be expected to decrease risk of recurrence...And for those with clear margins, there was excellent (100%) agreement between the Nomogram and the refined Oncotype DCIS score. Given the need for cost-based value in health care, and given the cost-free availability of a validated predictive online DCIS nomogram, rigorous evaluation of predictive accuracy and proof of significant added clinical benefit should be performed and made available before any new expensive commercially available test is adopted for clinical use.

P=N/A; Trial completion date: Mar 2022 --> Dec 2022

P2; N=34 --> 12

This article reviews the current status and existing published literature on DCIS molecular-risk assessment tools and their potential for guiding postoperative RT recommendations in the BCT setting. In addition, current trials studying omission of definitive surgery for low-risk DCIS are discussed.

P=N/A; Trial primary completion date: Apr 2022 --> Apr 2023

P2; Trial completion date: Dec 2021 --> Dec 2024 | Trial primary completion date: Dec 2021 --> Dec 2023

"Ethics approval was obtained from the Institutional Review Boards of Albert Einstein College of Medicine (IRB 2014-3611), Kaiser Permanente Colorado, Kaiser Permanente Hawaii, Henry Ford Health System, Mayo Clinic, Marshfield Clinic Research Institute and Hackensack Meridian Health, and from Lifespan Research Protection Office. The study results will be presented at meetings and published in peer-reviewed journals."

P2, P3; These results are consistent with those recently published utilizing whole breast radiotherapy. Due to the small number of local recurrence events and limited follow-up time, further investigations are needed to confirm findings.

"Our results suggest that both presence of TILs and spatial arrangement or close proximity, touching or encircling DCIS may be predictive for recurrence."

P2b; Trial completion date: Jul 2019 --> Jul 2023 | Trial primary completion date: Jul 2019 --> Jul 2022

P2b; Not yet recruiting --> Recruiting

P2b; Initiation date: Mar 2017 --> Jun 2017