Newly diagnosed strongly ER-positive negative breast cancer Cancer Malignant neoplasm of breast
Conditions
Interventions
Patients will be randomised 1:1 upon joining the trial through an online platform to either the comparator arm or the intervention arm.
The intervention in this trial is endocrine treatment tablets o
up to 8 weeks permitted for trial purposes
2. Intervention arm – surgery after 6 +/- 1 months of endocrine treatment
Participants will complete quality-of-life questionnaires periodically during thei
Sponsors
University of Oxford
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 04/10/2024: Main study: 1. Female 2. Clinically post-menopausal, according to established local criteria, and suitable for an aromatase inhibitor 3. Strongly ER+; defined as Allred scores of 7 or 8 or equivalent* 4. Tumour size =15 mm 5. Suitable for surgery and radiotherapy 6. Unifocal, newly diagnosed breast cancer visible on USS Note: Satellite lesions =5 mm and =10 mm in distance from the edge of the primary lesion are permitted as long as they can be removed en bloc; 7. Participant is able and willing to give informed consent for participation in the trial 8. In the Investigator's opinion, is able to comply with all trial requirements * or equivalent may include a histochemical score (H-score) = 200. QRI (information study) Patients: 1. Patients approached for participation in the EndoNET study 2. Patient inclusions are the same as for the EndoNET study Healthcare professionals (HCPs) and research personnel (RPs): 1. HCPs or RPs involved in management, operation or recruitment for the EndoNET study 2. Trial management group (TMG) members with a role in planning/coordinating recruitment Current inclusion criteria as of 02/06/2023 to 04/10/2024: Main study: 1. Female 2. Clinically post-menopausal; including one of: 2.1. Amenorrhoea >12 months and an intact uterus 2.2. Bilateral oophorectomy 2.3. For those with a history of hysterectomy, or hormone replacement therapy (HRT) within 12 months, venous FSH levels classified as post-menopausal by the testing laboratory if any doubt 3. Unifocal, newly diagnosed breast cancer visible on USS 4. Strongly ER+; defined as Allred scores of 7 or 8 or equivalent* 5. HER2- by immunohistochemistry, or 2+ and not amplified by in situ hybridisation 6. T-stage 1, 2 or 3 (=15 mm) 7. Axillary N0-1 on diagnostic USS +/- negative fine-needle aspiration (FNA) or core biopsy 8. Suitable for surgery and radiotherapy 9. Chemotherapy unlikely to be indicated 10. Participant is able and willing to give informed consent for participation in the trial 11. In the Investigator's opinion, is able to comply with all trial requirements * or equivalent may include a histochemical score (H-score) = 200. QRI (information study) Patients: 1. Patients approached for participation in the EndoNET study 2. Patient inclusions are the same as for the EndoNET study Healthcare professionals (HCPs) and research personnel (RPs): 1. HCPs or RPs involved in management, operation or recruitment for the EndoNET study 2. Trial management group (TMG) members with a role in planning/coordinating recruitment Previous inclusion criteria: Main study: 1. Female 2. Clinically post-menopausal; including one of: 2.1. Amenorrhoea >12 months and an intact uterus 2.2. Bilateral oophorectomy 2.3. For those with a history of hysterectomy, or hormone replacement therapy (HRT) within 12 months, venous FSH levels classified as post-menopausal by the testing laboratory if any doubt 3. Unifocal, newly diagnosed breast cancer visible on USS 4. Strongly ER+; defined as Allred scores of 7 or 8 or equivalent 5. HER2- by immunohistochemistry, or 2+ and not amplified by in situ hybridisation 6. T-stage 2 or 3 (>2 cm) 7. Axillary N0-1 on diagnostic USS +/- negative fine-needle aspiration (FNA) or core biopsy 8. Suitable for surgery and radiotherapy 9. Chemotherapy unlikely to be indicated 10. Participant is able and willing to give informed consent for participation in the trial 11. In the Investigator's op
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 04/10/2024: Main study: The participant may not enter the trial if ANY of the following apply: 1. Bilateral breast cancer 2. cN3 disease 3. cT4 disease Note: T4 is defined as (i) chest wall (rib/intercostal) involvement (adherence/invasion to pectoralis is NOT an extension to the chest wall and is not defined as T4 here) or (ii) skin ulceration, skin nodules or oedema such as in inflammatory breast cancer. Dimpling of the skin, nipple retraction or other skin other changes without ulceration, nodules or oedema, do not make a tumour T4; 4. Metastatic breast cancer (Stage IV disease) 5. Chemotherapy or anti-HER-2 therapy for current breast cancer started or planned at the time of randomisation 6. Previous invasive malignancy within 5 years which is likely to affect the safety or efficacy assessment or compliance with the protocol or interpretation of results 7. Concurrent use (at the time of randomisation) of HRT or any other oestrogen-containing medication (including vaginal oestrogens) Note: Presence of Mirena coil at the time of randomisation is not an exclusion; 8. If clinically pre-menopausal, ovarian suppression/ablation for the purposes of trial entry is not permitted 9. Aromatase inhibitor endocrine treatment following current breast cancer diagnosis taken for longer than 14 days at time of randomization. QRI (information study): Patients: 1. Patient exclusions are the same as for the EndoNET study 2. Patient does not wish to have consultations recorded and/or participate in interview HCPs and RPs: 1. HCPs or RPs who do not wish to have consultations recorded and/or participate in interview Previous participant exclusion criteria: Main study: The participant may not enter the trial if ANY of the following apply: 1. Bilateral breast cancer 2. ER- or HER2+ 3. Stage IV disease (distant metastasis) 4. Previous neoadjuvant treatment for breast cancer 5. Previous invasive malignancy within 5 years other than basal cell carcinoma 6. Concurrent use (at the time of randomisation) of HRT or any other oestrogen-containing medication (including vaginal oestrogens) 7. Ovarian suppression/ablation for the purposes of trial entry not permitted QRI (information study): Patients: 1. Patient exclusions are the same as for the EndoNET study 2. Patient does not wish to have consultations recorded and/or participate in interview HCPs and RPs: 1. HCPs or RPs who do not wish to have consultations recorded and/or participate in interview
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 04/10/2024: Rates of breast conservation surgery measured using surgical burden data stored in patient records at 6 months (+/- 1 month) of NET Previous primary outcome measure: The EndoNET Trial has co-primary outcome measures: 1. Global HRQoL is measured by FACT-B at baseline, 6 weeks or post-operative, 5, 7, 12, and 15 months 2. Rates of breast conservation surgery measured using surgical data stored in patient records at 15 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Tumour response rates are measured by the RECIST scale (CR, PR, PD or SD) at 2-4 weeks, 3 and 5 months (intervention arm) 2. Tumour size, histological grade and lymph node status according to histology reports pre- and post-surgery 3. Health-related QoL is measured by FACT-B +4/ES, Breast-Q, EQ-5D-5L and Hopwood Body Image Scale at baseline, 6 weeks or post-operative, 5, 7, 12 and 15 months 4. Risk of relapse and ability to measure endocrine sensitivity according to PEPI score at baseline, 2-4 weeks and post-operative sample (intervention arm) 5. Post-surgical complications and endocrine treatment side effects reported at 2-4 weeks, 6 weeks (intervention arm), surgery, post-operative, 3, 5, 6, 12 and 15 months 6. Participant compliance to ET/NET is measured by the MARS-5 questionnaire at 2-4 weeks, 5 months and 15 months 7. Significance of Ki67 in the prognosis of breast cancer measured using Ki67 score in tumour sample(s) at baseline, after 2-4 weeks of endocrine treatment and at surgery (in comparator arm) 8. Surgical management of the breast using rates of re-excision and further surgery after lumpectomy, requirement for advanced lumpectomy and rates of reconstruction post-mastectomy, and radiotherapy post-operative and at 15 months 9. Surgical management of the axilla using rates of sentinel node biopsy, axillary clearance and radiotherapy post-operative and at 15 months 10. Rates of local and distance recurrence measured using data stored in patient records post-surgery, at 15 months and periodically for long-term follow up 11. Breast cancer specific and overall survival measured using data stored in patient records post-surgery, at 15 months and periodically for long-term follow up 12. Resource use, cost and cost-effectiveness of implementing intervention compared with current practice measured by the Health Care Use questionnaire at baseline, 7, 12 and 15 months 13. Accuracy of ultrasound (and MRI if available) for assessing initial disease extent and dete | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactSurgical Interventions Trials Unit (SITU)
Outcome results
None listed