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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: No endocrine therapy; Other: Endocrine therapy

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 Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marta Sienkiewicz, MSc; Phone Number: 613-737-7700; Email: msienkiewicz@ohri.ca
• Study Contact Backup: Name: Lisa Vandermeer, MSc; Phone Number: 613-737-7700; Email: lvandermeer@ohri.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Not yet recruiting
      • Cross Cancer Institute
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1G3
      • Active, not recruiting
      • Waterloo Regional Health Network
    • London, Ontario, Canada, N6C 2R5
      • Active, not recruiting
      • London Health Sciences Centre
    • Markham, Ontario, Canada, L3P 7P3
      • Active, not recruiting
      • Oak Valley Health
    • Ottawa, Ontario, Canada, K1H8L6
      • Recruiting
      • The Ottawa Hospital
      • Contact: Marie-France Savard, MD; Phone Number: 70170 6137377700; Email: msavard@toh.ca
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Active, not recruiting
      • Thunder Bay Regional Health Sciences Centre
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Active, not recruiting
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Active, not recruiting
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ≤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

Exclusion Criteria:

• Metastatic cancer

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omission of endocrine therapy	Other: No endocrine therapy; No endocrine therapy given
Active Comparator: Administration of endocrine therapy for at least 5 years	Other: Endocrine therapy; Endocrine therapy given for at least 5 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS) is the time from the date of surgery to the date of death due to any cause.	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	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	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Marie-France Savard, MD, Ottawa Hospital Research Institute

Publications and helpful links

General 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.
• Alzahrani 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.
• Savard 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.

Helpful Links

• The Rethinking Clinical Trials (REaCT) website

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2021
• Primary Completion (Estimated): May 1, 2036
• Study Completion (Estimated): May 1, 2036

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radiation therapy; Older patients; Adjuvant therapy; Endocrine therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: REaCT-70

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No