Randomised controlled trial evaluating effectiveness of neoadjuvant endocrine treatment in post-menopausal women
Newly diagnosed strongly ER-positive negative breast cancer
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 of a type known as aromatase inhibitors (AIs). All participants will start their endocrine treatment tablets for oral use: letrozole (2.5 mg/day), anastrozole (1 mg/day) or exemestane (25 mg/day) at randomisation. The endocrine treatment offered in both arms of the trial is the same but the timing of the surgery differs: 1. Comparator arm – surgery after 2-4 weeks of endocrine treatment; 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 their 15-month participation and rates of breast conservation surgery (lumpectomy) will be recorded. Participants will continue their adjuvant treatment including their endocrine treatment for 5-10 years as per their usual standard treatment.
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 will
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