Active Surveillance in Older Women With ER+ Breast Cancer

NCT ID: NCT07262138

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-11-01
• Study Completion Date: 2030-12-31

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.

Detailed Description

Breast cancer, like most cancers arising in adults, is a disease of aging. Age is one of the most important risk factors, with nearly one third of all breast cancer cases diagnosed in patients older than 70 years and a peak incidence occurring in the 60s to 70s. The vast majority of these cancers are estrogen receptor positive (ER+), and the proportion of ER+ tumors relative to other subtypes increases with age. Consistent with the favorable receptor status (high degree of ER expression with negative HER2 receptor), these tumors grow slowly and are often less aggressive than tumors in younger patients, reflecting that tumorigenesis in these patients may largely be due to chronic exposures to tumor-promoting stimuli.

A sizable proportion of older women - defined as those aged 70 years or older - continue screening mammography. Continuation of routine mammography in older patients can lead to overdiagnosis, which is the detection of cancers that would never have caused symptoms or affected lifespan. As breast cancer incidence rises with age but competing risks of death (like heart disease or other illnesses) also increase, many slow-growing tumors identified through screening may not require treatment. However, once diagnosed, these cancers often lead to unnecessary interventions such as surgery, radiation, or endocrine therapy, which carry physical and emotional burdens. Overdiagnosis can also create anxiety, reduce quality of life, and strain healthcare resources, especially when the benefits of early detection decline with age. Overdiagnosis typically encompasses multiple clinical scenarios: first, some tumors are biologically indolent, due to their genomics, tumor microenvironment, and systemic macroenvironment, and not preordained to grow, spread, or kill; second, some small tumors may have the biological potential to grow and spread but will not do so in the patient's lifetime.

The overall hypothesis of the ACTIVE trial is that management of small, screen-detected, ER+/HER2- tumors using an active surveillance is safe and feasible.

Conditions

Early Stage Estrogen Receptor (ER) Positive Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Active Surveillance

Intervention Type: 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.

Interventions

Active Surveillance

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.

Intervention Type: OTHER

Other Intervention Names

Active Monitoring

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).

• Minimum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Priscilla McAuliffe

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Priscilla F McAuliffe, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Neil Carleton, MD, PhD

Role: CONTACT

carletonn2@upmc.edu

412-266-1991

Facility Contacts

Neil Carleton, MD, PhD

Role: primary

carletonn2@upmc.edu

412-266-1991

References

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.

Reference Type: BACKGROUND

PMID: 35047868 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 40490477 (View on PubMed)

Other Identifiers

HCC 25-142

Identifier Type: -

Identifier Source: org_study_id