Active Surveillance in Older Women With ER+ Breast Cancer

NCT07262138 | Recruiting

• 1 other identifier: HCC 25-142
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

ACTIVE is a prospective, single-arm, phase I/IIa study examining an active surveillance strategy for small, screen-detected, luminal breast cancer. Patients aged 70 or older with clinical stage I ER+/HER2- breast cancer are eligible. The goal of this clinical trial is to learn if an active surveillance strategy (serial imaging rather than therapeutic intervention) is a safe approach to monitor small breast cancers. The main question to answer is the proportion of participants who experience tumor progression by 12 months.

Conditions

Early Stage Estrogen Receptor (ER) Positive Breast Cancer

Keywords

Early stage breast cancer; Stage I breast cancer; Estrogen receptor positive breast cancer; Breast cancer in older women

Outcome Measures

Primary Outcomes (1)

• 12 month rate of tumor progression

  Tumor progression is defined based on the following criteria: * For tumors initially staged at cT1a and cT1b, tumor progression is defined as a greater than or equal to 50% increase in the longest diameter of the target lesion, with reference to the longest diameter at the baseline time point (t = 0mo). * For tumors initially staged at cT1c, tumor progression is defined as a greater than or equal to 25% increase in the longest diameter of the target lesion, with reference to the longest diameter at the baseline time point (t = 0mo).

  12 months

Secondary Outcomes (3)

• Longitudinal quality of life assessment using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Breast Cancer Symptom Index - 16 Item Version (NCCN NFBSI-16)

  Up to 24 months

• Rate of enrollment acceptance

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

Study Arms (1)

Active surveillance group

Following diagnosis, patients enroll in the study and complete imaging assessments at 6 months and 12 months via breast and axillary ultrasound. Patients may opt to undergo additional ultrasound imaging of the breast and axillary at the 3 and 9 month marks. These timepoints are optional. If, at any point during the study, patients experience new breast symptoms such as pain, palpable mass in breast or axilla, rash/nodule to the skin of the breast, patients are encouraged to notify their local treating oncologist. Additional imaging outside of the protocol-directed schedule is allowable at the discretion of the local treating oncologist.

Other: Active Surveillance

Interventions

Active Surveillance OTHER

Active surveillance is achieved through serial breast and axillary ultrasound. This will occur in the absence of any concurrent treatment of the breast cancer with the goal of identifying if the tumor grows after 12 months of observation. Patients will undergo ultrasound at diagnosis, 6 months, and 12 months. They may receive optional ultrasounds at 3 months and 9 months. If patients do not experience a progression during the allotted study period, but decline to continue with active surveillance, they may undergo any local or systemic therapy at the discretion of their local treating oncologist. If the tumor reaches the pre-specified threshold for progression at the time of the protocol-directed imaging, patients will undergo standard of care breast cancer therapy. The type and extent of surgery, adjuvant and systemic therapy will be left to the local treating team.

Also known as: Active Monitoring

Active surveillance group

Eligibility Criteria

• Age: 70 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients aged 70 or older with clinical stage I ER+/HER2- breast cancer

You may qualify if:

• Women aged 70 years or older with a diagnosis of invasive breast cancer who have not undergone surgical resection of the primary invasive tumor and/or axillary lymph nodes, have not undertaken any systemic therapy, and have not received radiation therapy as a treatment for this diagnosis. Patients with invasive cancer that is identified after excisional biopsy for atypia are included.
• Tumors must have been identified through mammographic screening.
• cT1a or cT1b (≤ 1cm): Nottingham Grade I or II allowed entry.
• cT1c (\>1-2cm): only Nottingham Grade I allowed entry.
• Breast cancer must be ER positive and HER2 negative according to the definition below, as assessed by local pathology.
• ER is considered positive if there are ≥ 60% positive tumor nuclei in the samples.
• HER2 negativity is defined per the current ASCO/CAP Clinical Practice Guideline.
• Patients with cognitive impairment are eligible provided that a legal surrogate is able to sign informed consent for study participation.
• Archival tissue will be submitted for all participants. Tissue must be confirmed available prior to registration.

You may not qualify if:

• Prior anti-cancer therapy (e.g., endocrine therapy, chemotherapy, radiation therapy, or investigational therapy) for the current breast cancer diagnosis.
• Current breast cancer diagnosis that is deemed a recurrence, at the discretion of the treating investigator.
• Multifocal or multicentric disease.
• Patients with a history of contralateral DCIS, or ipsilateral or contralateral LCIS are not eligible. Patients with a history of any ipsilateral breast radiation are not eligible.
• Diagnosis of inflammatory breast cancer (T4d).
• Male breast cancer.
• Any concurrent severe and uncontrolled medical condition that, in the treating clinician's opinion, would pose unacceptable safety risks or compromise compliance with the protocol. Such conditions could include: impairment of gastrointestinal tract function or gastrointestinal disease that may significantly alter the absorption of oral medications (uncontrolled Crohn disease or ulcerative colitis, uncontrolled chronic nausea, vomiting diarrhea, malabsorption, or small bowel resection); severe liver impairment (Child-Pugh Class C).

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Related Publications (2)

• Carleton N, Nasrazadani A, Gade K, Beriwal S, Barry PN, Brufsky AM, Bhargava R, Berg WA, Zuley ML, van Londen GJ, Marroquin OC, Thull DL, Mai PL, Diego EJ, Lotze MT, Oesterreich S, McAuliffe PF, Lee AV. Personalising therapy for early-stage oestrogen receptor-positive breast cancer in older women. Lancet Healthy Longev. 2022 Jan;3(1):e54-e66. doi: 10.1016/s2666-7568(21)00280-4. Epub 2022 Jan 5.

  PMID: 35047868 BACKGROUND

• Carleton N, McAuliffe PF. Overdiagnosis, competing morbidity and tumour biology in older women with breast cancer: building a case for active monitoring. Nat Rev Clin Oncol. 2025 Sep;22(9):621-622. doi: 10.1038/s41571-025-01040-y. No abstract available.

  PMID: 40490477 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

PBMCs, serum, plasma for ctDNA analysis

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Priscilla F McAuliffe, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neil Carleton, MD, PhD

CONTACT

412-266-1991; carletonn2@upmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 3, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)