The PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer

This research study is a way of gaining new knowledge about whether patients can omit radiation treatment after undergoing a lumpectomy, also known as "breast conserving surgery". In this trial, we are attempting to identify which patients may not need radiation.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer Radiation
• Intervention / Treatment: Device: Prosigna

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational treatment to learn whether it is appropriate for treating a specific disease.

The purpose of this study is to determine whether certain patients between the ages of 50 and 75 can safely omit radiation treatment after having a lumpectomy.In this research study, the investigators are using standard laboratory tests along with the Prosigna test to see if certain patients can avoid radiation, without having a higher risk of the cancer coming back in the future.

A portion of the participant surgical specimen will be prospectively maintained for future study using institutionally-approved tissue banking procedures.

The FDA (the U.S. Food and Drug Administration) has cleared the Prosigna test for generating a risk category and numerical score to assess the risk of distant recurrence, and has cleared us to investigate the use of the Prosigna test for helping with decisions about radiation.

• Study Type: Interventional
• Enrollment (Actual): 671
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10065
      • Memorial Sloane Kettering Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed invasive breast cancer
• The primary tumor must be excised via breast conserving surgery ("lumpectomy") with negative margins ("no ink on tumor") or re-excision showing no residual disease in the re-excision specimen.
• The tumor must be ≤2 cm (T1) in the largest dimension.
• Immunohistochemical studies must demonstrate the tumor to be ER+ (≥10%) or PR+, HER2- and grade 1 or 2.
• The patient must have undergone either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) demonstrating pathologic node-negativity (pN0). However, patients with immunohistochemical evidence of isolated tumor cells in a lymph node [pN0(i+)] are eligible if no deposit >0.2mm is identified.
• Age: this study is open to patients between 50 and 75 years of age (inclusive). Patients younger than 50 years of age are excluded based on prior data suggesting a different natural history for breast cancers arising in premenopausal women (with different subtype and biologic distributions that may confound the current aims). Women older than 75 years of age are excluded from this protocol due to historical difficulties achieving robust follow-up in this population, along with competing comorbidities which have been shown to interfere with subsequent breast cancer monitoring and evaluation.
• ECOG performance status ≤2 (Karnofsky ≥60%)
• Life expectancy of >5 years per the clinical impression of the treating physician(s).
• Eligible for and willing to undergo a course of adjuvant endocrine therapy.

Exclusion Criteria:

• At the time of enrollment, subjects may not have had any prior systemic therapy for breast cancer, including chemotherapy, hormonal therapy or targeted biologic therapy. Similarly, chemotherapy or biologic therapy must not be part of the subsequent treatment plan.
• Clinical, radiographic or pathologic evidence of multicentric disease.
• Evidence of T4 disease (e.g., involvement of the chest wall, skin, dermal lymphatics, or inflammatory breast cancer).
• Grade 3 histology.
• Tumors in which the invasive component is present only as micro-invasion.
• Multicentric invasive or in site carcinoma
• Bilateral breast malignancy.
• Inability or unwillingness to tolerate endocrine therapy.
• Documented mutation of TP53, BRCA1, BRCA2, or other hereditary cancer syndromes.
• Significant comorbidity associated with an estimation of <5 remaining life years.
• Another diagnosis of malignancy within the 5 years preceding enrollment (excluding non-melanoma skin cancers or in situ cervical lesions, which are permitted).
• Inability to understand or provide informed consent.
• Current addictive or psychiatric disorder which may preclude protocol adherence.
• Prior breast or chest radiotherapy for any indication.
• Pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ineligible for omission of RT; Prosigna confirms intermediate- or high-risk score. Participants with intermediate- or high-risk scores will be ineligible for omission of radiotherapy (RT). Some patients with low-risk scores may elect to receive RT.	Device: Prosigna; Transcriptional profile of 50 genes used for risk stratification.; Other Names: PAM-50
Active Comparator: Eligible for omission of RT; Prosigna confirms low risk score. Participant will be eligible for omission of therapy and chooses to do so. Patient will receive adjuvant endocrine therapy.	Device: Prosigna; Transcriptional profile of 50 genes used for risk stratification.; Other Names: PAM-50

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Five-Year Risk of Local Regional Recurrence in the Ipsilateral Breast or Lymph Nodes in Women without Adjuvant Radiotherapy	Using information gathered from follow-up physical examinations and mammography, the 5-year risk of local regional recurrence in women who omit radiotherapy post-lumpectomy will be evaluated.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Five-Year Risk of Any Recurrence: Local, Regional or Distant	Using information gathered from follow-up physical examinations and mammography, the 5-year risk of any recurrence in women who omit radiotherapy post-lumpectomy will be evaluated.	5 years
Overall Survival	Using information gathered from follow-up appointments and other record sources, 5-year survival rates will be evaluated.	5 years
Disease-Free Survival	Using information gathered from follow-up physical exams, mammography and other imaging as necessary, the rate of disease-free status at 5 years will be evaluated.	5 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: NanoString Technologies, Inc.
• Investigators: Principal Investigator: Julia Wong, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Ho AY, Bellon JR. Overcoming Resistance - Omission of Radiotherapy for Low-Risk Breast Cancer. N Engl J Med. 2023 Feb 16;388(7):652-653. doi: 10.1056/NEJMe2216133. No abstract available.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: January 10, 2016
• First Submitted That Met QC Criteria: January 10, 2016
• First Posted (Estimated): January 12, 2016

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer Radiation; Radiotherapy for Favorable-Risk Breast cancer; Radiotherapy Omission
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 15-255

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No