LETROZOLE for Breast cancer | HR-positive HER2-negative breast cancer | Early breast cancer

Inclusion criteria

• {"criterion_text":"- Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient’s consent;"}
• {"criterion_text":"- Bilateral breast cancers are permitted provided the tumour(s) in one breast meets the eligibility criteria and the other, contralateral tumour is not ER negative and/or HER2 positive and not clinically significant, defined by both of the following: a.\tThe contralateral tumour does not fulfil the tumour size and lymph node eligibility criteria required for trial entry; i.e. the following are not acceptable: i.\tpresence of lymph node macro-metastases; ii.\ttumour size ≥50mm when there is no lymph node involvement. b.\tThe treating physician does not consider that the characteristics of the contralateral tumour alone justify consideration of adjuvant chemotherapy."}
• {"criterion_text":"- Fitness to receive adjuvant chemotherapy, as judged by the treating physician;"}
• {"criterion_text":"- Short term pre-surgical treatment with endocrine therapy, including in combination with non-cytotoxic agents, is allowed providing that the duration of treatment did not exceed 8 weeks;"}
• {"criterion_text":"- Patients affiliated with or a benifiting from the local social security system, health social security system, or other local regulatory requirements"}
• {"criterion_text":"- Patients must agree to use adequate contraception methods for the duration of study treatment and for the duration specified in the SmPC after completing the treatment, unless agreed with the treatment physician the safety of attempt a pregnancy, which could be possible after at least 18 months of endocrine therapy."}
• {"criterion_text":"- Premenopausal defined by patient that are not post-menopaused"}
• {"criterion_text":"- Female"}
• {"criterion_text":"- Age ≥ 35 years"}
• {"criterion_text":"- Diagnosis of invasive HR-positive (ER≥10% of tumour cells stained positive and any PR expression) HER2-negative (IHC score 0-1+ or 2+ with negative/non-amplified ISH) invasive breast cancer; ER and HER2 determination will be assessed according to latest ASCO/CAP or national guidelines (Kimberly H. Allison et al. 2020);"}
• {"criterion_text":"- Breast and axillary surgery completed ≤ 12 weeks from study entry and randomization;"}
• {"criterion_text":"- Availability of a Formalin-Fixed Paraffin-Embedded (FFPE) tumour sample from surgery to perform Prosigna® analysis or slides."}
• {"criterion_text":"- Tumour size and axillary lymph node status. One of the following must apply: a.\t1-3 lymph nodes involved AND any invasive tumour size. b.\tnode negative (including micrometastases in at least 1 node [i.e. deposit >0.2-2mm diameter]) AND invasive tumour size ≥ 50mm."}
• {"criterion_text":"- Multiple ipsilateral breast cancers are permitted provided that at least one tumour meets the tumour size and axillary lymph node entry criteria, and none meet any of the exclusion criteria."}

Exclusion criteria

• {"criterion_text":"- Postmenopausal women. Women who fulfil the following criteria at trial entry will be considered postmenopausal: a.\tAge >45 and natural amenorrhoea of at least 1 year’s duration. b.\tBilateral surgical oophorectomy. c.\tFor amenorrhoea not fulfilling the above criteria the diagnosis of postmenopausal status should be supported by hormone measurement: FSH levels must be > 25IU/L with low oestradiol (i.e. within the locally defined postmenopausal range), in the event of doubt measured on 2 occasions preferably 4-6 weeks apart. This applies to women who have undergone hysterectomy without bilateral surgical oophorectomy and are age <60; those ≥60 may be considered postmenopausal."}
• {"criterion_text":"- Stage IV breast cancer;"}
• {"criterion_text":"- Start of adjuvant systemic treatment (except for neoadjuvant endocrine therapy for a duration ≤ 8 weeks) before trial entry*;"}
• {"criterion_text":"- Previous diagnosis of malignancy except: a.\tPrevious ductal carcinoma in situ (DCIS) or pleomorphic lobular carcinoma in situ (LCIS) of the breast managed by local treatment only; b.\tPrevious in situ carcinoma as defined by the International Classification of Diseases for Oncology (ICD-O) including basal cell carcinoma of skin and cervical intraepithelial neoplasia; c.\tPrevious invasive malignancy managed by local treatment only AND disease-free for at least 10 years."}
• {"criterion_text":"- Patients enrolled in another interventional therapeutic trial within 30 days of inclusion;"}
• {"criterion_text":"- Presence of concomitant medical and/or psychiatric comorbidities and/or social problems that might prevent informed consent, treatment compliance or follow up;"}
• {"criterion_text":"- Person deprived of their liberty or under protective custody or guardianship."}
• {"criterion_text":"- Pregnant women or women who are breast-feeding at inclusion."}
• {"criterion_text":"- Patients unwilling or unable to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures because of geographic, familial, social, or psychological reasons."}

Primary endpoints

• {"endpoint_text":"- Invasive Breast Cancer Free Survival (IBCFS) in the global population, defined according to the STEEP version 2.0 system (Tolaney et al., JCO 2021) as the time from the date of randomization to the date of the first event of ipsilateral loco-regional invasive breast cancer recurrence, distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause.","definition_or_measurement_approach":"Defined according to the STEEP version 2.0 system (Tolaney et al., JCO 2021): time from randomization to first event of ipsilateral loco-regional invasive breast cancer recurrence, distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- Same as primary enpoint but restricted to with tumours for which the Prosigna® score is below the cut-off (≤60) for chemotherapy use (approximately 70% of the total).","definition_or_measurement_approach":"Same IBCFS definition (STEEP v2.0) applied to subgroup with Prosigna® score ≤60."}
• {"endpoint_text":"- According to the STEEP version 2.0 system definition, in the global population : Distant recurrence free interval (DRFI), Distant recurrence free survival (DRFS), Breast cancer specific survival (BCSS)","definition_or_measurement_approach":"DRFI, DRFS, BCSS defined per STEEP v2.0 criteria."}
• {"endpoint_text":"- According to the STEEP version 2.0 system definition, in the global population with tumours for which the Prosigna® score is ≤60 : Distant recurrence free interval (DRFI), Distant recurrence free survival (DRFS), Breast cancer specific survival (BCSS), Overall survival (OS)","definition_or_measurement_approach":"DRFI, DRFS, BCSS, OS as per STEEP v2.0 in Prosigna® ≤60 subgroup."}
• {"endpoint_text":"- QoL, physical and psychosocial symptoms and breast cancer frequent symptoms/side effects will be assessed in OPTIMA-YOUNG population* and in OPTIMA-YOUNG population with tumours for which the Prosigna® score is ≤60 using the following questionnaires: Quality of life (EORTC QLQ-C30 and BR42), Anxiety and Depression (GAD-7 and PHQ8), Cognition (FACT Cog), NCCN Distress thermometer, Return to work","definition_or_measurement_approach":"Patient-reported outcome questionnaires: EORTC QLQ-C30 & BR42 for QoL; GAD-7 and PHQ8 for anxiety/depression; FACT-Cog for cognition; NCCN Distress Thermometer; return-to-work metrics."}
• {"endpoint_text":"- Health and safety outcomes: osteoporosis (Number non-traumatic fractures), cardiovascular disease (Number of major cardiovascular events, including stroke, MI, heart failure, cardiovascular deaths), fertility (Number of pregnancies) and health behaviour : physical Activity Levels (IPAQ), BMI, tobacco and alcohol consumption Self-reported adherence to ET (VOILS) in OPTIMA-YOUNG population* and in OPTIMA-YOUNG population with tumours for which the Prosigna® score is ≤60","definition_or_measurement_approach":"Safety outcomes tracked as event counts (non-traumatic fractures; major CV events incl. stroke, MI, heart failure, CV deaths); fertility measured by number of pregnancies; health behaviours via IPAQ, BMI, self-reported tobacco/alcohol; adherence via VOILS."}
• {"endpoint_text":"- Communication aspects, uncertainties and fears related to participating in a de-escalation trial will be assessed using the following questionnaires : Fear of Cancer Recurrence (FCRI-SF), Motivation to enter the trial (SPECIFIC), Recall and expectation on potential treatment related toxicities (ad hoc questionnaire), Decision Conflict (SURE), Decision Regret Scale (DRS) in the OPTIMA-YOUNG population*.","definition_or_measurement_approach":"Psychosocial/decision metrics via listed validated questionnaires (FCRI-SF, SPECIFIC, ad hoc toxicity recall, SURE, DRS)."}
• {"endpoint_text":"- Cost-effectiveness analysis of Prosigna®-driven treatment compared to standard clinical practice, summarised as the incremental cost-effectiveness ratio in the patients recruited in France, Italy, Spain for the OPTIMA-YOUNG trial and United Kingdom for OPTIMA.","definition_or_measurement_approach":"Health economic analysis producing incremental cost-effectiveness ratio (QALYs via EQ-5D-5L); country-specific analyses for France, Italy, Spain (OPTIMA-YOUNG) and UK (OPTIMA)."}
• {"endpoint_text":"- Score of perceived ease of use (SUS) of the digital platform (WeShare) for research on the OPTIMA-YOUNG population*.","definition_or_measurement_approach":"System Usability Scale (SUS) score for WeShare platform among participants."}

Methods

• Patient-facing printed materials: flyers and posters (country-specific patient flyers/posters listed in recruitment documents).
• Website patient pages / online recruitment material (patient-facing website content documented per country).
• Patient-facing videos and video scripts for recruitment (patient videos listed for multiple countries).
• Letters to general practitioners / primary care (e.g. 'Lettera al MMG_IT_for publication' for Italy).
• Hospital/clinic site-based recruitment through participating oncology centres (site lists provided for each country).

Greece

Earliest CTIS Part Ii Submission Date

16-06-2025

Latest Decision Or Authorization Date

23-09-2025

Processing Time Days

99

Number Of Sites

6

Number Of Participants

160

Italy

Earliest CTIS Part Ii Submission Date

08-09-2025

Latest Decision Or Authorization Date

23-09-2025

Processing Time Days

15

Number Of Sites

22

Number Of Participants

500

Spain

Earliest CTIS Part Ii Submission Date

04-09-2025

Latest Decision Or Authorization Date

24-09-2025

Processing Time Days

20

Number Of Sites

11

Number Of Participants

250

Poland

Earliest CTIS Part Ii Submission Date

29-08-2025

Latest Decision Or Authorization Date

27-09-2025

Processing Time Days

29

Number Of Sites

7

Number Of Participants

200

Belgium

Earliest CTIS Part Ii Submission Date

09-01-2026

Latest Decision Or Authorization Date

29-01-2026

Processing Time Days

20

Number Of Sites

7

Number Of Participants

100

Ireland

Earliest CTIS Part Ii Submission Date

18-08-2025

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

203

Number Of Sites

8

Number Of Participants

160

France

Earliest CTIS Part Ii Submission Date

21-07-2025

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

249

Number Of Sites

33

Number Of Participants

900

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France