Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomised, Multicentre Trial Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer (REaCT-70)

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: No endocrine therapy
* Other: Endocrine therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omission of endocrine therapy<br>Omission of endocrine therapy | Other: No endocrine therapy<br>* No endocrine therapy given<br>|
| Active Comparator: Administration of endocrine therapy for at least 5 years<br>Administration of endocrine therapy for at least 5 years | Other: Endocrine therapy<br>* Endocrine therapy given for at least 5 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accrual of 100 participants across 8 centres within 2 years | The accrual of at least 100 participants at 8 centres within 2 years. | 2 years after study initiation | 
| Participation rate of at least 60% | A participation rate of at least 60% among participants approached. | 2 years after study initiation | 
| 90% treatment allocation rate | At least 90% of enrolled participants receive treatment as per their allocated intervention for at least 4 weeks | 4 weeks after study enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Significant adverse events | Significant adverse events (e.g. bone fracture, stroke/transient ischemic attack, thromboembolic event, cardiac event, second cancer, hospitalization and death) | Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment | 
| Endocrine therapy related toxicity | Endocrine therapy (ET) related toxicity based upon Common Terminology for Adverse Events version 5 (CTCAEv5) | Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment | 
| Health-related quality of life scores | 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. | Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment | 
| Rate of treatment discontinuation | The rate of endocrine therapy treatment discontinuations and reasons why the endocrine therapy treatment was discontinued. | 5 years after study enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation therapy, Endocrine therapy, Older patients, Adjuvant therapy