Breast CancerPhase 4NCT04921137
Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer
A Phase 4 study testing No endocrine therapy and Endocrine therapy in people with Breast Cancer, run by Ottawa Hospital Research Institute at 8 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- No endocrine therapy and Endocrine therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 8 sitesCanada
- Study dates
- 19 Aug 2021to May 2036
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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 ≤3 cm on microscope exam, OR Grade 2 and ≤2 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 node-negative (cN0 or pN0)
- Able to provide oral consent and complete questionnaires in French or English as per study protocol
Who cannot join
- Metastatic cancer
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Canada8 sites, 2 recruiting
- Not yet recruiting
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
- Active, not recruiting
Waterloo Regional Health Network
Kitchener, Ontario, N2G 1G3
- Active, not recruiting
London Health Sciences Centre
London, Ontario, N6C 2R5
- Active, not recruiting
Oak Valley Health
Markham, Ontario, L3P 7P3
- Recruiting
The Ottawa Hospital
Ottawa, Ontario, K1H8L6
- Active, not recruiting
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
- Active, not recruiting
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
- Active, not recruiting
Thunder Bay Regional Health Sciences Centre
Thunder Bay, Ontario, P7B 6V4
About this study
Official title: A Randomised, Multicentre Trial Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer (REaCT-70)
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- No endocrine therapy, Endocrine therapy
- Keywords
- Radiation therapy, Endocrine therapy, Older patients, Adjuvant therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No endocrine therapyOther
No endocrine therapy given
Endocrine therapyOther
Endocrine therapy given for at least 5 years
| Study group | Role | What they receive |
|---|---|---|
| Omission of endocrine therapy | Experimental | Omission of endocrine therapy Receives: Other: No endocrine therapy |
| Administration of endocrine therapy for at least 5 years | Active comparator | Administration of endocrine therapy for at least 5 years Receives: Other: Endocrine therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hierarchical composite endpoint (OS, iDFS, MDFS, QoL)
The primary outcome is a hierarchical composite endpoint following the WIN-ratio approach. This composite endpoint includes overall survival (OS), invasive disease free survival (iDFS), metastatic disease free survival (MDFS), quality of life (QoL), joint pain, and hot flashes.
Measured: 5 years
Secondary outcomes (14)
Overall survival
Overall survival (OS) is the time from the date of surgery to the date of death due to any cause.
Measured: 5 years
Invasive disease free survival
Invasive disease free suvival (iDFS) is the time from the surgery until the first occurrence of invasive ipsilateral, loco-regional, contralateral and distant breast tumor recurrence or death due to any cause
Measured: 5 years
Metastatic disease free survival
Metastatic disease free survival (MDFS) is the time from the surgery until the first occurrence of distant breast tumor recurrence of death due to any causes
Measured: 5 years
Health-related quality of life: FACT-B plus ES
Health-related quality of life is measured using the Functional Assessment of Cancer Therapy - Breast (FACT-B) plus the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES). The FACT-B has a total score of 0 to 148. FACT-ES has a total score of 0 to 184. Higher scores indicate better quality of life.
Measured: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Hot flashes
Hot flashes measured using the validated FACT-B plus ES (questions ES1-3). Worsening of hot flashes will be defined as an increase by 1 of the hot flashes score compared to baseline. Improvement will be defined as a decrease of 1 of the hot flashes score compared to baseline.
Measured: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Joint pain
Joint pain measured using the validated FACT-B plus ES (question BRM1). Worsening of join pain will be defined as an increase by 1 of the joint pain score compared to baseline. Improvement of join pain will be defined as a decrease of 1 of the the join pain score compared to baseline.
Measured: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Health-related quality of life: FACT-G
Health-related quality of life will be measured with the Functional Assessment of Cancer Therapy - General (FACT-G) 27-item questionnaire. FACT-G scores range from 0 to 108. Higher scores indicate better quality of life.
Measured: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Health-related quality of life: EQ-5D-5L
The EQ-5D-5L questionnaire includes 6 self-reported quality of life items.
Measured: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Breast Cancer Specific Survival
Breast Cancer Specific Survival (BCSS) is the time from the date of surgery to the date of death from the breast cancer.
Measured: 5 years
Adverse events of interest
The number of participants with each adverse events of interest: bone fracture, cerebrovascular event, thromboembolic event, cardiovascular event, secondary cancer, hospitalization and death.
Measured: 5 years
Change in geriatric domains
Change in geriatric domains (e.g. functional status, comorbidities, medications, nutritional status, cognitive function, and psychosocial status) using CARG score patient tool.
Measured: Baseline, 1 year, 5 years
Adherence with prescribed endocrine therapy
Adherence with prescribed endocrine therapy will be measured by the validated Five-Item Medication Adherence Report Scale (MARS-5 score) in Arm B only.
Measured: 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Quality-adjusted life years (QALY)
QALYs are estimated by multiplying the time spent in each health state by the corresponding utility value and summing these values across all model cycles over the time horizon.
Measured: 5 years
Beliefs about Medicine Questionnaire - adjuvant endocrine therapy (BMQ-AET)
Participants in arm B will complete the Beliefs about Medicine Questionnaire - adjuvant endocrine therapy (BMQ-AET). This includes 10 self-reported items.
Measured: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start19 Aug 2021
- Primary completionMay 2036 (estimated)
- Study completionMay 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marie-France Savard, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04921137
- Sponsor's protocol ID
- REaCT-70
- Status last verified
- May 2026
- First submitted
- 27 May 2021
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Savard MF, Clemons M, Hutton B, Jemaan Alzahrani M, Caudrelier JM, Vandermeer L, Liu M, Saunders D, Sienkiewicz M, Stober C, Cole K, Shorr R, Arnaout A, Chang L. De-escalating adjuvant therapies in older patients with lower risk estrogen receptor-positive breast cancer treated with breast-conserving surgery: A systematic review and meta-analysis. Cancer Treat Rev. 2021 Sep;99:102254. doi: 10.1016/j.ctrv.2021.102254. Epub 2021 Jun 19.
PubMed 34242928Alzahrani M, Clemons M, Chang L, Vendermeer L, Arnaout A, Larocque G, Cole K, Hsu T, Saunders D, Savard MF. Management Strategies for Older Patients with Low-Risk Early-Stage Breast Cancer: A Physician Survey. Curr Oncol. 2021 Dec 21;29(1):1-13. doi: 10.3390/curroncol29010001.
PubMed 35049675Savard MF, Alzahrani MJ, Saunders D, Chang L, Arnaout A, Ng TL, Brackstone M, Vandermeer L, Hsu T, Awan AA, Cole K, Larocque G, Clemons M. Experiences and Perceptions of Older Adults with Lower-Risk Hormone Receptor-Positive Breast Cancer about Adjuvant Radiotherapy and Endocrine Therapy: A Patient Survey. Curr Oncol. 2021 Dec 8;28(6):5215-5226. doi: 10.3390/curroncol28060436.
PubMed 34940075
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Multicentre Trial Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer (REaCT-70)
- ClinicalTrials.gov ID
- NCT04921137
- Acronym / sponsor ID
- REaCT-70
- Conditions
- Breast Cancer
- Keywords
- Radiation therapy, Endocrine therapy, Older patients, Adjuvant therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 19 Aug 2021 (actual)
- Primary completion
- May 2036 (estimated)
- Study completion
- May 2036 (estimated)
- First posted
- 10 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Omission of endocrine therapy | Experimental | Other: No endocrine therapyOmission of endocrine therapy |
| Administration of endocrine therapy for at least 5 years | Active comparator | Other: Endocrine therapyAdministration of endocrine therapy for at least 5 years |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- 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 ≤3 cm on microscope exam, OR Grade 2 and ≤2 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 node-negative (cN0 or pN0)
- Able to provide oral consent and complete questionnaires in French or English as per study protocol
Key exclusion criteria (1 listed)
- Metastatic cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No endocrine therapyNo endocrine therapy given | Other | Omission of endocrine therapy |
| Endocrine therapyEndocrine therapy given for at least 5 years | Other | Administration of endocrine therapy for at least 5 years |
Primary outcome
Hierarchical composite endpoint (OS, iDFS, MDFS, QoL)
Time frame: 5 years
The primary outcome is a hierarchical composite endpoint following the WIN-ratio approach. This composite endpoint includes overall survival (OS), invasive disease free survival (iDFS), metastatic disease free survival (MDFS), quality of life (QoL), joint pain, and hot flashes.
14 secondary outcomes
Overall survival
Time frame: 5 years
Invasive disease free survival
Time frame: 5 years
Metastatic disease free survival
Time frame: 5 years
Health-related quality of life: FACT-B plus ES
Time frame: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Hot flashes
Time frame: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Joint pain
Time frame: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Health-related quality of life: FACT-G
Time frame: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Health-related quality of life: EQ-5D-5L
Time frame: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Breast Cancer Specific Survival
Time frame: 5 years
Adverse events of interest
Time frame: 5 years
Change in geriatric domains
Time frame: Baseline, 1 year, 5 years
Adherence with prescribed endocrine therapy
Time frame: 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Quality-adjusted life years (QALY)
Time frame: 5 years
Beliefs about Medicine Questionnaire - adjuvant endocrine therapy (BMQ-AET)
Time frame: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Background: PubMed 34242928Savard MF, Clemons M, Hutton B, Jemaan Alzahrani M, Caudrelier JM, Vandermeer L, Liu M, Saunders D, Sienkiewicz M, Stober C, Cole K, Shorr R, Arnaout A, Chang L. De-escalating adjuvant therapies in older patients with lower risk estrogen receptor-positive breast cancer treated with breast-conserving surgery: A systematic review and meta-analysis. Cancer Treat Rev. 2021 Sep;99:102254. doi: 10.1016/j.ctrv.2021.102254. Epub 2021 Jun 19.
- Background: PubMed 35049675Alzahrani M, Clemons M, Chang L, Vendermeer L, Arnaout A, Larocque G, Cole K, Hsu T, Saunders D, Savard MF. Management Strategies for Older Patients with Low-Risk Early-Stage Breast Cancer: A Physician Survey. Curr Oncol. 2021 Dec 21;29(1):1-13. doi: 10.3390/curroncol29010001.
- Background: PubMed 34940075Savard MF, Alzahrani MJ, Saunders D, Chang L, Arnaout A, Ng TL, Brackstone M, Vandermeer L, Hsu T, Awan AA, Cole K, Larocque G, Clemons M. Experiences and Perceptions of Older Adults with Lower-Risk Hormone Receptor-Positive Breast Cancer about Adjuvant Radiotherapy and Endocrine Therapy: A Patient Survey. Curr Oncol. 2021 Dec 8;28(6):5215-5226. doi: 10.3390/curroncol28060436.
- The Rethinking Clinical Trials (REaCT) websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marie-France Savard, MD principal investigator
Ottawa Hospital Research Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing No endocrine therapy and Endocrine therapy in people with Breast Cancer, run by Ottawa Hospital Research Institute at 8 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lisa Vandermeer, MSc (613-737-7700, lvandermeer@ohri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hierarchical composite endpoint (OS, iDFS, MDFS, QoL) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04921137, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.