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 (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lisa Vandermeer, MSc; Phone Number: 73039 613-737-7700; Email: lvandermeer@toh.ca
• Study Contact Backup: Name: Marta Sienkiewicz, MSc; Phone Number: 613-737-7700; Email: msienkiewicz@ohri.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • Recruiting
      • The Ottawa Hospital
      • Contact: Marie-France Savard, MD; Phone Number: 70170 6137377700; Email: msavard@toh.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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 ≤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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

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
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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 19, 2021
• Primary Completion (ANTICIPATED): September 1, 2023
• Study Completion (ANTICIPATED): September 1, 2024

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): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Radiation therapy; Older patients; Adjuvant therapy; Endocrine therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast 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