NCT07106632

Brief Summary

Rationale: Around 70 to 80% of breast cancers are so-called "hormone-dependent" (HR+)/HER2-. For more than 50 years, studies have shown that chemotherapy and optimised hormonal treatments (hormone therapy), including a drug associated with ovarian suppression (OFS), improve survival in patients with these cancers, which are characterised by a high risk of relapse. However, younger patients suffer more side effects than older women, particularly from chemotherapy. This can affect their quality of life and reduce their ability to work. For post-menopausal women, genetic tests exist to assess whether chemotherapy is really necessary in addition to hormonal treatment. However, for high-risk premenopausal patients, chemotherapy is still systematically recommended, as no study has proved that it can be safely avoided. Clinical trials based on risk stratification using genetic tests have not been conclusive, but the majority of premenopausal women included had not received optimal hormone treatment. It is possible that the beneficial effect of chemotherapy is partly due to the artificial menopause it induces. Some experts believe that, for patients with a high clinical risk but a low genetic risk, an optimised hormonal treatment (drug + OFS) could suffice, without the need for chemotherapy. Objectives: Main objective: The aim of the study is to determine whether the use of a genetic test (Prosigna®) to decide whether or not to administer chemotherapy produces results as good as standard treatment (systematic chemotherapy) in premenopausal women with hormone-dependent (HR+) breast cancer/HER2-, by assessing their risk of cancer recurrence. The secondary objectives include verifying whether, in patients with a low Prosigna® score (around 70% of cases), optimised hormonal treatment (including suppression of ovarian function) is as effective as chemotherapy combined with hormonal in treatment preventing cancer recurrence. The study also seeks to compare the efficacy of treatment Prosigna®-guided versus systematic chemotherapy in terms of recurrence and quality of life, as well as economic aspects. Finally, the aim is to understand patients' concerns about the concept of reducing treatment (therapeutic de-escalation) and the way in which this information is communicated to them. The primary endpoint of the study is to measure the time elapsed between the start of participation in the study and the appearance of an event indicating a return of the cancer. This includes the return of cancer in the same breast or neighbouring areas, the spread of cancer to other parts of the body, the appearance of new cancer in the other breast or death from any cause. Trial Population: The study includes women major premenopausal diagnosed with invasive, hormone receptor-positive (ER+) and HER2-negative breast cancer. Patients must have undergone breast and axillary surgery recent and have a tumour sample suitable for analysis by the testProsigna® . They must be able to receive the study treatments Postmenopausal women, women with stage IV breast cancer, women who have already received adjuvant systemic treatment (except short neoadjuvant hormone therapy), women with a recent history of invasive cancer, pregnant women or women who are breast-feeding will not be able to take part in the study. Interventions: After agreeing to take part, patients will enter the pre-inclusion period (up to 28 days before randomisation), during which the investigator will carry out all the necessary tests to assess their eligibility. The investigator will then randomise the patients to find out which treatment they have been assigned, no more than 2 weeks later: the experimental group will receive a treatment decided on the basis of the results of a genomic test: either chemotherapy and hormone therapy, or hormone therapy alone. The control group will receive the standard treatment. The treatment and follow-up phases are the same as for standard care. Information on the quality of life patient's will and other information (associated costs, perception of their participation in the study, etc.) also be collected by means of questionnaires completed by the patients during the 5 years following randomisation.

Trial Health

70
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,380

participants targeted

Target at P75+ for phase_3

Timeline
150mo left

Started Apr 2026

Longer than P75 for phase_3

Geographic Reach
7 countries

105 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress1%
Apr 2026Aug 2038

First Submitted

Initial submission to the registry

June 11, 2025

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 6, 2025

Completed
8 months until next milestone

Study Start

First participant enrolled

April 1, 2026

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 15, 2031

Expected
7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2038

Last Updated

March 24, 2026

Status Verified

September 1, 2025

Enrollment Period

5.4 years

First QC Date

June 11, 2025

Last Update Submit

March 23, 2026

Conditions

Keywords

Adjuvant therapy de-intensificationCare deliveryQuality of LifePremenopausal WomenRisk stratification

Outcome Measures

Primary Outcomes (1)

  • invasive breast cancer free survival (IBCFS)

    Invasive Breast Cancer Free Survival (IBCFS), is 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.

    Time from the date of randomization to the date of the first event (ipsilateral loco-regional invasive breast or distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause), assessed up to 120 months

Secondary Outcomes (33)

  • Invasive Breast Cancer Free Survival (IBCFS) in the population with tumours for which the Prosigna® score is below 60

    Time from the date of randomization to the date of the first event (ipsilateral loco-regional invasive breast or distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause), assessed up to 120 months

  • Distant recurrence free interval (DRFI)

    time from the date of randomization to the date of the first event of distant recurrence of breast cancer or death from breast cancer in the global population, assessed up to 120 months

  • Distant recurrence free survival (DRFS)

    time from the date of randomization to the date of the first event of distant recurrence of breast cancer or death from any cause in the global population, assessed up to 120 months

  • Breast cancer specific survival (BCSS)

    time from the date of randomization to the date of death from breast cancer in the global population, assessed up to 120 months

  • Overall survival (OS)

    time from the date of randomization to the date of death from any cause in the global population, assessed up to 120 months

  • +28 more secondary outcomes

Study Arms (2)

Control Arm

ACTIVE COMPARATOR
Drug: In the control arm, the treatment will be as standard of care : chemo-endocrine therapy

Experimental Arm

EXPERIMENTAL
Drug: test-directed treatment: allocated treatment will depend on the PAM50 score result (centrally assessed) : chemo-endocrine therapy or endocrine therapy alone

Interventions

In this experimental arm, the treatment is driven by the score of the Prosigna test. If the score is superior to 60, the patient is considered at hight risk so the patient will receive chemo-endocrine therapy. If the result is under or equal to 60, only endocrine therapy will be prescribed to the patient.

Experimental Arm

Standard treatment: Chemotherapy followed by endocrine therapy

Control Arm

Eligibility Criteria

Age35 Years - 45 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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;
  • Premenopausal defined by patient that are not post-menopaused
  • Female
  • Age ≥ 35 years
  • 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;
  • Breast and axillary surgery completed ≤ 12 weeks from study entry and randomization;
  • Availability of a Formalin-Fixed Paraffin-Embedded (FFPE) tumour sample from surgery to perform Prosigna® analysis or slides.
  • Note: in case of receipt of neoadjuvant endocrine therapy the Prosigna® test must be done on the baseline biopsy. Performing the test on the surgical piece or on on-treatment biopsy is not permitted.
  • Tumour size and axillary lymph node status. One of the following must apply:
  • lymph nodes involved AND any invasive tumour size.
  • node negative (including micrometastases in at least 1 node \[i.e. deposit \>0.2-2mm diameter\]) AND invasive tumour size ≥ 50mm.

You may not qualify if:

  • 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:
  • The 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. presence of lymph node macro-metastases; .ii. tumour size ≥50mm when there is no lymph node involvement.
  • The treating physician does not consider that the characteristics of the contralateral tumour alone justify consideration of adjuvant chemotherapy.
  • Fitness to receive adjuvant chemotherapy, as judged by the treating physician;
  • 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;
  • Patients affiliated with or a beneficiary of the local social security system, health social security system, or other local regulatory requirements
  • 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.
  • Note : patient with extracapsular nodular transgression are eligible. NOTE: If neoadjuvant endocrine therapy was received, the Prosigna® test must be realized on the baseline biopsy. Performing the test on the surgical specimen or on biopsy taken during treatment is not permitted.
  • NOTE: Re-excision or complementary mastectomy for close/positive surgical margins should be postponed after chemotherapy completion, if chemotherapy is given; breast reconstruction is allowed after trial entry.
  • NOTE: The use of approved adjuvant targeted agents (abemaciclib, ribociclib and olaparib) combined to adjuvant endocrine therapy is allowed according to local practice recommendations and availability.
  • \. Postmenopausal women. Women who fulfil the following criteria at trial entry will be considered postmenopausal:
  • Age \>45 and natural amenorrhoea of at least 1 year's duration.
  • Bilateral surgical oophorectomy.
  • For 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.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (105)

Institut Jules Bordet

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, B-6060, Belgium

Location

CHU Helora Hôpital de La Louvière - Site Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

CHU UCL Namur - Site Sainte Elisabeth

Namur, 5000, Belgium

Location

Clinique Saint Pierre

Ottignies, 1340, Belgium

Location

CHR Verviers

Verviers, 4800, Belgium

Location

Centre Hospitalier d'Auxerre

Auxerre, 89000, France

Location

Sainte Catherine - Institut du Cancer Avignon-Provence

Avignon, 84918, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64100, France

Location

Centre Hospitalier Simone Veil de Beauvais

Beauvais, 60021, France

Location

Hôpital de Blois

Blois, 41000, France

Location

Avicenne Hospital (APHP)

Bobigny, 93000, France

Location

Clinique Tivoli

Bordeaux, 33000, France

Location

Centre Hospitalier Fleyriat Bourg en Bresse

Bourg-en-Bresse, 01012, France

Location

Clinique Pasteur - CFRO

Brest, 29200, France

Location

Groupement Hospitalier Est - Hospices Civils de Lyon

Bron, 69500, France

Location

Centre Francois Baclesse

Caen, 14000, France

Location

Centre Hospitalier Métropole Savoie

Chambéry, 73000, France

Location

CH Cholet

Cholet, 49300, France

Location

Pôle Santé République

Clermont-Ferrand, 63000, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Léonard De Vinci

Dechy, 59187, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

CH Annecy Genevois

Épagny Metz-Tessy, 74370, France

Location

Centre Hospitalier Intercommunal de Fréjus Saint Raphael

Fréjus, 83600, France

Location

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, 38028, France

Location

Centre Hospitalier Le Mans - Centre De Cancérologie De La Sarthe

Le Mans, 72000, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

CHU de Limoges

Limoges, 87042, France

Location

Hôpital de la croix Rousse - Hospices Civils de Lyon

Lyon, 69004, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital Européen

Marseille, 13003, France

Location

Hôpital Privé Clairval

Marseille, 13009, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Hôpital Privé Nancy Lorraine

Nancy, 54000, France

Location

Hôpital Privé du Confluent

Nantes, 44277, France

Location

Centre Hospitalier de Pau

Pau, 64000, France

Location

Hôpital Lyon Sud-Hospices Civils de Lyon

Pierre-Bénite, 69495, France

Location

Hôpital NOVO - Site de Pontoise

Pontoise, 95300, France

Location

Institut Godinot

Reims, 51100, France

Location

CLCC Eugène Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, 76000, France

Location

Clinique Mutualiste de l'Estuaire

Saint-Nazaire, 44600, France

Location

CHU de Saint Etienne

Saint-Priest-en-Jarez, 42000, France

Location

Clinique Médico Chirurgicale Charcot

Sainte-Foy-lès-Lyon, 69110, France

Location

Strasbourg Oncologie Libérale - Clinique Sainte Anne

Strasbourg, 67000, France

Location

Hôpitaux du Léman

Thonon-les-Bains, 74200, France

Location

Oncopole Claudius Regaud, IUCT-Oncopole

Toulouse, 31059, France

Location

Clinique Pasteur

Toulouse, 31076, France

Location

CHU Tours

Tours, 37000, France

Location

Centre de cancérologie Les Dentellières

Valenciennes, 59300, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

University Hospital 'Aretaieio'

Athens, GR 115 28, Greece

Location

University General Hospital 'Attikon'

Athens, GR 124 62, Greece

Location

Hygeia Hospital

Athens, GR 151 23, Greece

Location

IASO Hospital

Athens, GR 151 23, Greece

Location

Metropolitan Hospital

Athens, GR 185 47, Greece

Location

Cork University Hospital

Cork, T12 DC4A, Ireland

Location

Mater Misericordiae University Hospital

Dublin, D07 A8NN, Ireland

Location

Mater Private Hospital

Dublin, D07 WKW8, Ireland

Location

St James's Hospital

Dublin, D08 NHY1, Ireland

Location

University Hospital Limerick

Limerick, V94 F858, Ireland

Location

Midland Regional Hospital Tullamore

Tullamore, R35 NY51, Ireland

Location

University Hospital Waterford

Waterford, X91 ER8E, Ireland

Location

Centro Di Riferimento Oncologico Di Aviano

Aviano, 33081, Italy

Location

ASS Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

AUSL di Modena - Ospedale B. Ramazzini

Carpi, 41012, Italy

Location

ASST Ospedale Maggiore di Crema

Crema, 26013, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

ASST Lecco - P.O. A. Manzoni

Lecco, 23900, Italy

Location

IRCCS Istituto Romagnolo per lo Studio Dei Tumori (IRST) "Dino Amadori"

Meldola, 47014, Italy

Location

Fondazione IRCCS Istituto Nazionale Dei Tumori

Milan, 20133, Italy

Location

A.O.U Policlinico di Modena

Modena, 41124, Italy

Location

IRCCS San Gerardo

Monza, 20900, Italy

Location

A.O.U. Federico II - Policlinico

Naples, 80131, Italy

Location

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Naples, 80131, Italy

Location

Istituto Oncologico Veneto

Padua, 35128, Italy

Location

A.O.U. di Parma

Parma, 43126, Italy

Location

A.O. di Perugia - Ospedale S. Maria della Misericordia

Perugia, 06132, Italy

Location

"OSPEDALE P. PEDERZOLI" Casa di Cura Privata S.p.A.

Peschiera del Garda, 37019, Italy

Location

AUSL Della Romagna

Ravenna, 48121, Italy

Location

AUSL - IRCCS di Reggio Emilia

Reggio Emilia, 420123, Italy

Location

AUSL della Romagna - Ospedale Infermi di Rimini

Rimini, 47923, Italy

Location

A.O.U. Policlinico Umberto I

Roma, 00161, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Klinika Onkologii I Radioterapii Universeryteckie Centrum Kliniczne- Gdansk

Gdansk, 80-214, Poland

Location

MSC National Research Institute Of Oncology

Gliwice, 44-102, Poland

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

Location

ZP ZOZ Opolskie Centrum Onkologii im.prof. Tadeusza Koszarowskiego

Opole, 45-061, Poland

Location

Oncology Clinic, University Clinical Hospital in Pozan, Medical University

Poznan, 60-569, Poland

Location

Zachodniopomorskie Centrum Onkologii

Szczecin, 71-730, Poland

Location

Militray Institute of Medicine

Warsaw, 04-141, Poland

Location

Hospital General Universitario Dr. Balmis

Alicante, 03010, Spain

Location

Hospital Clinic De Barcelona

Barcelona, 08036, Spain

Location

Consorcio Hospitalario Provincial De Castellon

Castillón, 12006, Spain

Location

Hospital Universitario Virgen De Las Nieves

Granada, 18014, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada

Manresa, 08243, Spain

Location

University Hospital Son Espases

Palma, 07120, Spain

Location

Hospital Universitario Virgen De La Macarena

Seville, 41009, Spain

Location

University Hospital Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital General Universitario De Valencia

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Ines Vaz-Luis

    Gustave Roussy, Cancer Campus, Grand Paris

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanhecke

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 11, 2025

First Posted

August 6, 2025

Study Start

April 1, 2026

Primary Completion (Estimated)

August 15, 2031

Study Completion (Estimated)

August 15, 2038

Last Updated

March 24, 2026

Record last verified: 2025-09

Locations