Table 1.

Summary of the ongoing clinical trials involving biomarkers or biosignature for DCIS.

Trial ID	Status	Title	Inclusion Criteria	Endpoint and Primary Outcome Measure	Estimated/Actual Primary Completion Date
NCT02492607	Active, recruiting	Management of Low-Risk Ductal Carcinoma in Situ (Low-risk DCIS): a Non-randomized, Multicenter, Non-inferiority Trial, Between Standard Therapy Approach Versus Active Surveillance (LORD)	Pure and low-grade DCIS ≥45 years old Any menopausal status Pure and low-grade DCIS	Endpoint: efficacy of active surveillance vs conventional treatment for low-risk DCIS Primary outcome measure: ipsilateral invasive breast tumour-free rate at 10 years	December 2029
NCT02926911	Active, not recruiting	Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low-Risk DCIS: A Phase III Prospective Randomized Trial	Unilateral, bilateral, unifocal, or multifocal DCIS without invasive breast cancer ≥40 years old ECOG 0 or 1 No contraindication for surgery ER (+) and/or PR (+) by IHC HER2 0, 1+ or 2+ by IHC	Endpoint: efficacy of active surveillance ± endocrine therapy vs conventional treatment for low-risk DCIS Primary outcome measure: ipsilateral invasive cancer rate at 2 years	July 2028
ISRCTN27544579	Active, not recruiting	Surgery versus Active Monitoring for LOw RISk Ductal Carcinoma in Situ (DCIS (LORIS))	≥46 years old Non-high-grade DCIS	Endpoint: whether patients with low-risk DCIS can safely avoid surgery and whether patients who do require surgery can be identified by pathological and radiological means Primary outcome measure: Ipsilateral invasive breast cancer-free survival rate at 5 years	March 2030
NCT04916808	Active, recruiting	The AUS-PREDICT Registry for DCIS Patients with DCISionRT Testing (AUS-PREDICT)	≥25 years old DCISionRT™ test Histologically confirmed DCIS in a single breast Eligible for breast-conserving treatment	Endpoint: utility of the DCISionRT™ test in the diagnosis and treatment of DCIS. Primary outcome measure: change in treatment recommendations after the test results	May 2024
NCT02872025	Active, recruiting	Testing the Ability of Immunotherapy to Alter the Tumor Immune MicroEnvionment (TIME) and Reduce or Eradicate High Risk DCIS	≥18 years old 2 or more high-risk DCIS features (grade II-III, palpable mass, negative hormone receptor-negative, Her2 positive, young age (≤45 years), lesion greater than 5 cm) Extensive DCIS and a small component of invasive disease History of tamoxifen and/or aromatase inhibitor ECOG 0 to 1	Endpoint: change in the immune microenvironment of high-risk DCIS after immunotherapy. Primary outcome measure: efficacy and safety of intralesional mRNA-2752 administration measured by the change in the MRI tumour size/volume/enhancement	March 2024
NCT04797299	Active, recruiting	Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk Ductal Carcinoma in Situ Defined by a Molecular Expression Assay Combined With Clinico-Pathological Features (ELISA)	>45 years old DCIS without microinvasion Tumour size ≤ 2.5 cm BCS with clear resection margins ≥ 2 mm or no residual disease on re-excision Oncotype DX DCIS score with a predicted 10-year risk of LR ≤ 10%	Endpoint: whether the combination of clinicopathological factors and the use of the Oncotype DX DCIS score can avoid radiation Primary outcome measure: Ipsilateral local recurrence	March 2035
NCT06075953	Active, recruiting	DCIS: RECAST Trial -Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: a Breast Cancer Prevention Pilot Study	≥18 years old Previous diagnosis of HR+ DCIS (at least 50% ER or PR and 2+;) with or without microinvasion	Endpoint: whether active surveillance monitoring and hormonal therapy in DCIS patients can be an effective management of the disease Primary outcome measure: Fraction of patients remaining on active surveillance at 7 months compared to control	November 2028
NCT03878342	Active, recruiting	Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast (ROMANCE)	≥50 years old ECOG ≤ 2 Microcalcifications on pre-biopsy mammography, unifocal, ≤25 mm or opacity without microcalcifications and no clinical palpable tumour Absence of suspicious residual microcalcifications Breast-conserving surgical excision Non-invasive DCIS Free margins (≥2 mm), or free margins following re-excision Low or intermediate nuclear grade Absence of extensive necrosis (≤30% of the lumen diameter) Immunohistochemical characteristics of luminal A subtype: ER ≥ 10%, PR ≥ 20%, HER2 negative (0/1+) or 2+ not amplified, Ki67 < 15%	Endpoint: use biological markers to identify subgroups of patients who could safely avoid RT Primary outcome measure: 5-year cumulative incidence of in-breast cancer recurrences	November 2029