Trial Information

Adjuvant Systemic Treatment for Oestrogen-receptor (ER)-Positive HER2-negative Breast Carcinoma in Women Over 70 According to Genomic Grade (GG): Chemotherapy + Endocrine Treatment Versus Endocrine Treatment. A French UNICANCER Geriatric Oncology Group (GERICO) and Breast Group (UCBG) Multicentre Phase III Trial

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.