Clinical trial NCT04921137: Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Breast Cancer
Keywords: Radiation therapy
Endocrine therapy
Older patients
Adjuvant therapy
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2021-06-10
Enrollment: 109
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Accrual of 100 participants across 8 centres within 2 years
timeFrame: 2 years after study initiation
measure: Participation rate of at least 60%
timeFrame: 2 years after study initiation
measure: 90% treatment allocation rate
timeFrame: 4 weeks after study enrolment
Secondary outcomes:
measure: Significant adverse events
timeFrame: Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment
measure: Endocrine therapy related toxicity
timeFrame: Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment
measure: Health-related quality of life scores
timeFrame: Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years and 5 years after study enrolment
measure: Rate of treatment discontinuation
timeFrame: 5 years after study enrolment
Other outcomes:
Locations:
city: Kitchener
country: Canada
facility: Grand River Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Markham
country: Canada
facility: Oak Valley Health
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Marie-France Savard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.