Adjuvant Systemic Treatment for (ER)-Positive HER2-negative Breast Carcinoma in Women Over 70 According to Genomic Grade (GG): Chemotherapy + Endocrine Treatment Versus Endocrine Treatment

NCT ID: NCT01564056

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1989 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-12
• Study Completion Date: 2026-03-31

Brief Summary

The purpose of the study is to evaluate the benefit of adjuvant chemotherapy on overall survival for elderly patients with breast cancer, in a sub group with a high risk of relapse according to Genomic Grade test.

Detailed Description

The purpose of this trial is to address the question of the added value of adjuvant chemotherapy on survival in 70+ BC patients with ER+ disease, deemed "at risk of relapse" (pN+ or pN0 with a high prognostic classifier, namely GG by RT-PCR) and planned to receive as well adjuvant endocrine treatment. This benefit will be weighed with the competition exerted by comorbidities on mortality.

As in many recently developed trials evaluating specific strategies for the elderly (e.g. CALGB 49907 (8); bevacizumab and colorectal cancer in the PRODIGE 20 elderly program supported by the PHRC 2010), the choice of chemotherapy regimen will be left to the investigator between 3 "standard" ones: TC x 4 (no anthracyclines), AC x 4 or MC x 4 (better cardiac tolerance), in order to obtain enrolment of a less highly selected population, more representative of the general population to the difference of the high selection classically observed in standard oncology trials.

In parallel, patients not included in the randomized part (whatever reason) and treated with adjuvant endocrine treatment only will be followed up as a separate observational cohort.

1. Screening All women 70+ having undergone surgery for invasive pN0 or pN+, ER+ HER2- BC, will be screened and invited to participate. Pre-selection will be possible pre-operatively.

2. Prognostic signature After having signed a written informed consent, the prognostic signature Genomic Grade (GG) will be assessed by RT-PCR.

3. Randomization (Group I) Only the patients with a Genomic Grade (GG) considered as high will be randomized (1:1): endocrine treatment only (Arm A) versus endocrine treatment + adjuvant chemotherapy (Arm B).

Randomization1:1 between arm A and B will be done using minimization stratified according to pN status (pN+ vs pN0), G8 (≤ vs > 14), and center.

Given (i) the high potential of less cardiotoxic regimen including liposomal formulations for anthracyclines or excluding anthracyclines and (ii) the wish to capture the whole population to depict the heterogeneity of ageing from 70, adjuvant chemotherapy (Arm B) will be left to the choice of investigator amongst 3 standard regimen of same duration, 4 cycles given every 3 weeks + primary prophylactic GCSF:

• AC = doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m²
• TC = docetaxel 75 mg/m² + cyclophosphamide 600 mg/m²
• MC = liposomal non pegylated doxorubicin (Myocet) 60 mg/m² + cyclophosphamide 600 mg/m²

4. Patients not randomized (Group II) Patients not randomized for any reason (low GG, randomization refusal or treatment refusal, etc.) will enter a surveillance program and will be able to participate to other specific geriatric studies (GERICO project to evaluate the impact of comprehensive geriatric assessment on quality of life, treatment administered and BC survival after 75 years; EORTC study to validate the scale specifically developed for elderly ELD15).

The Group II will present a triple interest and will participate, together with randomized patients, to achieve the following objectives:

• validation of the prognostic value of Genomic Grade and performance of the test in the elderly BC population, as compared to standardized routine histopathological parameters,
• translational studies to identify molecular signatures,
• collection of descriptive data including comorbidities and polymedication.

5. Endocrine treatment and radiotherapy In both Groups (I and II), the endocrine treatment will be left to the choice of the investigator (tamoxifen, aromatase inhibitor or sequential) and radiotherapy will follow standard guidelines.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: ENDOCRINE TREATMENT

HORMONOTHERAPY (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).

Group Type: OTHER

HORMONOTHERAPY

Intervention Type: DRUG

Hormonotherapy will be administered during 5 years following chemotherapy when allocated.

(Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).

Arm B: CHEMOTHERAPY + ENDOCRINE TREATMENT

HORMONOTHERAPY (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).

CHEMOTHERAPY regimen will be chosen amongst the following ones:

• TC (docetaxel + cyclophosphamide)
• AC (doxorubicin + cyclophosphamide)
• MC (liposomal non pegylated doxorubicin [Myocet®]+ cyclophosphamide)

Group Type: EXPERIMENTAL

CHEMOTHERAPY then HORMONOTHERAPY

Intervention Type: DRUG

CHEMOTHERAPY regimen will be chosen amongst the following ones:

i) 4 cycles of TC (docetaxel + cyclophosphamide)

• Docetaxel 75 mg/m² IV infusion at hospital every 21 days
• Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days

ii) 4 cycles of AC (doxorubicin + cyclophosphamide)

• Doxorubicin 60 mg/m² IV infusion at hospital every 21 days
• Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days

iii) 4 cycles of MC (liposomal non pegylated doxorubicin [Myocet®]+ cyclophosphamide)

• Myocet® 60 mg/m² IV infusion at hospital every 21 days
• Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days

HORMONOTHERAPY (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).

Interventions

HORMONOTHERAPY

Hormonotherapy will be administered during 5 years following chemotherapy when allocated.

(Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).

Intervention Type: DRUG

CHEMOTHERAPY then HORMONOTHERAPY

CHEMOTHERAPY regimen will be chosen amongst the following ones:

i) 4 cycles of TC (docetaxel + cyclophosphamide)

• Docetaxel 75 mg/m² IV infusion at hospital every 21 days
• Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days

ii) 4 cycles of AC (doxorubicin + cyclophosphamide)

• Doxorubicin 60 mg/m² IV infusion at hospital every 21 days
• Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days

iii) 4 cycles of MC (liposomal non pegylated doxorubicin [Myocet®]+ cyclophosphamide)

• Myocet® 60 mg/m² IV infusion at hospital every 21 days
• Cyclophosphamide 600 mg/m² IV infusion at hospital every 21 days

HORMONOTHERAPY (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women aged ≥ 70 yo,
• Histologically proven invasive breast cancer (regardless of the type),
• Complete surgery performed before enrolment: radical modified mastectomy or breast conservative surgery, with either a sentinel lymph node procedure or axillary lymph node dissection,
• Any N status (pN+ or pN0),
• No clinically or radiologically detectable metastases (M0),
• Oestrogen receptor (ER)-positive, as defined by a ≥ 10% tumor stained cells by immunohistochemistry (IHC),
• HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative),
• Normal haematological function: ANC ≥ 1,500/mm3; platelets count ≥ 100,000/mm3; haemoglobin > 9 g/dl,
• Normal hepatic function: total bilirubin ≤ 1.25 ULN; ASAT and ALAT ≤ 1.5 ULN; alkaline phosphatases ≤ 3 ULN,
• Creatinine clearance (MDRD formula) ≥ 40 mL/min,
• PS (ECOG) ≤ 2,
• Patient able to comply with the protocol,
• Patients must have signed a written informed consent form prior to any study specific procedures, including the agreement for the use of archived tumoral material for genomic screening and data collection,
• Patients must be affiliated to a Social Health Insurance.

Exclusion Criteria

• Any metastatic impairment, including homolateral sub-clavicular node involvement, regardless of its type,
• Any tumor ≥ T4a (UICC1987) (cutaneous invasion, deep adherence, inflammatory breast cancer),
• ER-negative breast cancer (i.e. <10% tumor stained cells by IHC),
• HER2 overexpression, defined as IHC score 3+ or score 2+ and FISH/SISH/CISH positive,
• Any chemotherapy, hormonal therapy or radiotherapy for breast cancer before surgery,
• PS (ECOG) ≥ 3,
• Any specific contra-indication to the study drugs (including but not limited to hypersensitivity to the study drugs or their components),
• Patient deprived of freedom or under tutelage,
• Patient unable to comply with the required medical follow-up for geographic, social or psychological reasons.

• Minimum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Etienne Brain

Role: PRINCIPAL_INVESTIGATOR

Institut Curie, Saint Cloud

Locations

Clinique du Sud Luxembourg

Arlon, , Belgium

Cliniques universitaires Saint-Luc - UCL

Brussels, , Belgium

Grand Hopital de Charleroi (GHdC)

Charleroi, , Belgium

Hôpital INDC entité Jolimontoise

Haine-Saint-Paul, , Belgium

Centre Hospitalier de l'Ardenne

Libramont, , Belgium

CHC - Les Cliniques Saint-Joseph

Liège, , Belgium

CHU Ambroise Paré

Mons, , Belgium

Clinique et Maternité Sainte-Elisabeth

Namur, , Belgium

Cliniques Saint-Pierre Ottignies

Ottignies, , Belgium

Centre Hôspitalier de Wallonie Picarde (CHWAPI)

Tournai, , Belgium

CHPLT Verviers

Verviers, , Belgium

CHU Mont-Godinne

Yvoir, , Belgium

Clinique Claude Bernard

Albi, , France

Centre Paul Papin

Angers, , France

CH d'Ardèche méridionale

Aubenas, , France

Institut Sainte Catherine

Avignon, , France

Polyclinique Urbain V

Avignon, , France

Hôpital Avicenne

Bobigny, , France

Institut Bergonié

Bordeaux, , France

CHU de Brest

Brest, , France

Centre François Baclesse

Caen, , France

Centre Hospitalier René Dubos

Cergy-Pontoise, , France

CH de Cholet

Cholet, , France

Hôpital Antoine Béclère

Clamart, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre Hospitalier Alpes Léman

Contamine-sur-Arve, , France

Groupement Hospitalier Public du Sud de l'Oise - site de Creil

Creil, , France

CHI de Créteil

Créteil, , France

Hôpital Henri Mondor

Créteil, , France

CH de Dax

Dax, , France

Centre d'oncologie et de radiothérapie du Parc

Dijon, , France

Centre Georges-François Leclerc

Dijon, , France

CH Jean Monnet

Épinal, , France

Clinique Sainte Marguerite

Hyères, , France

CHD de Vendée

La Roche-sur-Yon, , France

CH de Lagny sur Marne

Lagny-sur-Marne, , France

CH du Mans

Le Mans, , France

Clinique Victor Hugo

Le Mans, , France

Clinique Hartmann

Levallois-Perret, , France

Centre Oscar Lambret

Lille, , France

CHU de Limoges

Limoges, , France

Centre Hospitalier de Bretagne Sud

Lorient, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli-Calmettes

Marseille, , France

CH de Mâcon - Les Chanaux

Mâcon, , France

Centre Hospitalier Intercommunal de Meulan - Les Mureaux

Meulan-en-Yvelines, , France

CH Layné

Mont-de-Marsan, , France

Clinique du Pont de Chaume

Montauban, , France

Centre Val d'Aurelle - Paul Lamarque

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

CHR d'Orléans

Orléans, , France

Groupe Hospitalier Paris St Joseph

Paris, , France

Groupe Hospitalier des Diaconesses - Croix Saint Simon

Paris, , France

Institut Curie - Hôpital Claudius Regaud

Paris, , France

Polyclinique de Francheville

Périgueux, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

CHU de Poitiers

Poitiers, , France

CH de la Région d'Annecy

Pringy, , France

Institut du Cancer Courlancy

Reims, , France

Institut Jean Godinot

Reims, , France

Centre Eugène Marquis

Rennes, , France

CH de Rodez

Rodez, , France

Centre Henri Becquerel

Rouen, , France

Clinique Mathilde

Rouen, , France

Institut Curie - Hôpital René Huguenin

Saint-Cloud, , France

CHI Poissy Saint Germain

Saint-Germain-en-Laye, , France

CHP Saint Grégoire

Saint-Grégoire, , France

ICO -Centre René Gauducheau

Saint-Herblain, , France

Clinique Mutualiste de l'Estuaire

Saint-Nazaire, , France

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, , France

RISSA Sarcelles (GCS Recherche & Innovation Santé Sarcelles)

Sarcelles, , France

CH de Senlis

Senlis, , France

Centre Paul Strauss

Strasbourg, , France

Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Strasbourg Oncologie Libérale

Strasbourg, , France

Hopitaux du Léman

Thonon-les-Bains, , France

CHI de Toulon - Hopital Sainte Musse

Toulon, , France

Clinique Pasteur

Toulouse, , France

Clinique Saint Jean du Languedoc

Toulouse, , France

Institut Claudius Regaud

Toulouse, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Centre Saint Yves

Vannes, , France

CH Bretagne Atlantique

Vannes, , France

Institut Gustave Roussy

Villejuif, , France

Countries

Belgium; France

References

Brain E, Mir O, Bourbouloux E, Rigal O, Ferrero JM, Kirscher S, Allouache D, D'Hondt V, Savoye AM, Durando X, Duhoux FP, Venat-Bouvet L, Blot E, Canon JL, Rollot-Trad F, Bonnefoi H, Roque T, Lemonnier J, Latouche A, Henriques J, Lacroix-Triki M, Vernerey D; GERICO&UCBG/Unicancer. Adjuvant chemotherapy and hormonotherapy versus adjuvant hormonotherapy alone for women aged 70 years and older with high-risk breast cancer based on the genomic grade index (ASTER 70s): a randomised phase 3 trial. Lancet. 2025 Aug 2;406(10502):489-500. doi: 10.1016/S0140-6736(25)00832-3.

Reference Type: DERIVED

PMID: 40752909 (View on PubMed)

Other Identifiers

2011-004744-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UC-0103/1102

Identifier Type: OTHER

Identifier Source: secondary_id

GERICO11/PACS10

Identifier Type: -

Identifier Source: org_study_id