Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer
Study Details
Study Description
Brief Summary
The current standard of care for stage 1 hormone receptor-positive (HR+) breast cancer consists of breast-conserving surgery followed by adjuvant radiotherapy (RT) and endocrine therapy (ET) for at least 5 years. The benefit of adjuvant ET for older patients is mitigated because of their increase risk of death from other causes and shorter time horizon to live. Clinical and pathological factors such as low-intermediate grade, tumor size ≤2 cm, and older age have been used in a few studies to identify patients with a lower risk of recurrence that might benefit from adjuvant therapy de-escalation, i.e. omission of RT or ET. Since there is no dedicated randomized clinical trial (RCT) conducted to evaluate the omission of ET, there is clinical equipoise as to whether we can omit adjuvant ET in older patients with lower-risk early-stage breast cancer. Therefore, we propose a randomised, multicentre trial evaluating harms and benefits of endocrine therapy in patients ≥70 years of age with lower risk breast cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
The current standard of care for stage 1 hormone receptor-positive (HR+) breast cancer consists of breast-conserving surgery followed by adjuvant radiotherapy (RT) and endocrine therapy (ET) for at least 5 years. The benefit of adjuvant ET for older patients is mitigated because of their increase risk of death from other causes and shorter time horizon to live. This population is also more likely to have additional comorbidities which can lead to higher treatment-related adverse events impacting quality of life and precipitating functional decline. Clinical and pathological factors such as low-intermediate grade, tumor size ≤2 cm, and older age have been used in a few studies to identify patients with a lower risk of recurrence that might benefit from adjuvant therapy de-escalation, i.e. omission of RT or ET. The body of evidence from small prospective studies, mathematical modelling study and retrospective analyses would suggest that the omission of ET in older patients with favourable HR+ breast cancer who had optimal local therapy (i.e. breast conserving surgery followed by adjuvant radiotherapy) does not compromise locoregional and survival outcomes. Since there is no dedicated randomized clinical trial (RCT) conducted to evaluate the omission of ET, there is clinical equipoise as to whether we can omit adjuvant ET in older patients with lower-risk early-stage breast cancer. Therefore, we propose a randomised, multicentre trial evaluating harms and benefits of endocrine therapy in patients ≥70 years of age with lower risk breast cancer.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Omission of endocrine therapy Omission of endocrine therapy |
Other: No endocrine therapy
No endocrine therapy given
|
| Active Comparator: Administration of endocrine therapy for at least 5 years Administration of endocrine therapy for at least 5 years |
Other: Endocrine therapy
Endocrine therapy given for at least 5 years
|
Outcome Measures
Primary Outcome Measures
- Accrual of 100 participants across 8 centres within 2 years [2 years after study initiation]
The accrual of at least 100 participants at 8 centres within 2 years.
- Participation rate of at least 60% [2 years after study initiation]
A participation rate of at least 60% among participants approached.
- 90% treatment allocation rate [4 weeks after study enrolment]
At least 90% of enrolled participants receive treatment as per their allocated intervention for at least 4 weeks
Secondary Outcome Measures
- Significant adverse events [Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment]
Significant adverse events (e.g. bone fracture, stroke/transient ischemic attack, thromboembolic event, cardiac event, second cancer, hospitalization and death)
- Endocrine therapy related toxicity [Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment]
Endocrine therapy (ET) related toxicity based upon Common Terminology for Adverse Events version 5 (CTCAEv5)
- Health-related quality of life scores [Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment]
Health-related quality of life (HR-QoL) scores measured by the Cancer and Aging Research Group geriatric assessment (patient-tool) and the Functional Assessment of Cancer Therapy - Endocrine Symptom Subscale (FACT-B plus ES). The Cancer and Aging Research Group geriatric assessment tool (patient-tool) is utilized to capture information about a patient's medical history as well as functional, cognitive and psychosocial status. The FACT-B plus ES is used to measure the side effects and putative benefits of hormonal treatment given in breast cancer.
- Rate of treatment discontinuation [5 years after study enrolment]
The rate of endocrine therapy treatment discontinuations and reasons why the endocrine therapy treatment was discontinued.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
New invasive estrogen and/or progesterone receptor-positive (ER+ and/or PR+), HER2-negative (HER2-) invasive breast carcinoma diagnosis as per ASCO-CAP guidelines
-
The primary tumour characteristics are either: Grade 1 and ≤5 cm on microscope exam, OR Grade 2 and ≤3 cm on microscope exam, OR Grade 3 and ≤1 cm on microscope exam
-
Treated with standard loco-regional therapy: breast conserving surgery followed by adjuvant radiotherapy OR total mastectomy
-
Axillary lymph node-negative (N0)
-
Able to provide oral consent and complete questionnaires in French or English as per study protocol
Exclusion Criteria:
- Metastatic cancer
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Ottawa Hospital | Ottawa | Ontario | Canada | K1H8L6 |
Sponsors and Collaborators
- Ottawa Hospital Research Institute
Investigators
- Principal Investigator: Marie-France Savard, MD, Ottawa Hospital Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- REaCT-70