TEST:

Oncotype DX Breast DCIS Score test

P=N/A, N=526, Recruiting, Ontario Clinical Oncology Group (OCOG) | Trial completion date: May 2035 --> Nov 2035 | Trial primary completion date: Mar 2035 --> Nov 2030

The Oncotype test changed treatment recommendations regarding adjuvant RT in almost a third of patients. Additionally, the assay was associated with reduced treatment-related decisional conflict and anxiety in patients. LR risk predictions by oncologists were higher than the Oncotype predictions highlighting a need for additional tools to aid decision-making.

Overall, the adoption of the DCIS Score in patients within the NCDB since 2018 has been low and appears to be decreasing. However, the DCIS Score appears to have clinical utility regarding adjuvant RT in patients that have undergone BCS and DCIS Score receipt was also associated with higher rates of BCS alone. Use of personalized tools such as the DCIS Score should be encouraged to help patients and physicians optimize adjuvant radiation therapy use for DCIS.

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.

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.

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.

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

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.