Breast Cancer
Conditions
Keywords
Radiation therapy, Endocrine therapy, Older patients, Adjuvant therapy
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.
Interventions
OTHERNo endocrine therapy
No endocrine therapy given
OTHEREndocrine therapy
Endocrine therapy given for at least 5 years
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hierarchical composite endpoint (OS, iDFS, MDFS, QoL) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 5 years | Overall survival (OS) is the time from the date of surgery to the date of death due to any cause. |
| Invasive disease free survival | 5 years | 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 |
| Metastatic disease free survival | 5 years | 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 |
| Health-related quality of life: FACT-B plus ES | Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years | 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. |
| Hot flashes | Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years | 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. |
| Joint pain | Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years | 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. |
| Health-related quality of life: FACT-G | Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years | 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. |
| Health-related quality of life: EQ-5D-5L | Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years | The EQ-5D-5L questionnaire includes 6 self-reported quality of life items. |
| Breast Cancer Specific Survival | 5 years | Breast Cancer Specific Survival (BCSS) is the time from the date of surgery to the date of death from the breast cancer. |
| Adverse events of interest | 5 years | The number of participants with each adverse events of interest: bone fracture, cerebrovascular event, thromboembolic event, cardiovascular event, secondary cancer, hospitalization and death. |
| Change in geriatric domains | Baseline, 1 year, 5 years | Change in geriatric domains (e.g. functional status, comorbidities, medications, nutritional status, cognitive function, and psychosocial status) using CARG score patient tool. |
| Adherence with prescribed endocrine therapy | 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years | Adherence with prescribed endocrine therapy will be measured by the validated Five-Item Medication Adherence Report Scale (MARS-5 score) in Arm B only. |
| Quality-adjusted life years (QALY) | 5 years | 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. |
| Beliefs about Medicine Questionnaire - adjuvant endocrine therapy (BMQ-AET) | Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years | Participants in arm B will complete the Beliefs about Medicine Questionnaire - adjuvant endocrine therapy (BMQ-AET). This includes 10 self-reported items. |
Countries
Canada
Contacts
CONTACTLisa Vandermeer, MSc
CONTACTMarta Sienkiewicz, MSc
PRINCIPAL_INVESTIGATORMarie-France Savard, MD
Ottawa Hospital Research Institute
Outcome results
None listed