Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bone Density Conservation Agents

Docetaxel

Cyclophosphamide

Tamoxifen

Doxorubicin

Liposomal doxorubicin

Estrogens

Aromatase Inhibitors

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

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)

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).

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).

CHEMOTHERAPY then HORMONOTHERAPY

Etienne Brain

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.

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.

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

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 OS is defined as the interval between the date of randomization and the date of death from any cause.

The specific OS is defined as the interval between the date of randomization and the date of death due to cancer. Alive patients or dead patients from another cause will be censored at the last follow-up

The DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first.

The EFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or the date of second neoplasia, or the date of death from any cause, whichever occurs first.

The National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

the geriatric questionnaires (CCI \& listing comedications, G8, IADL or MMSE) will be completed by a geriatrician or a person trained to geriatric assessment before randomization, at the end of the chemotherapy in arm B or 16 weeks after the randomization in arm A (endocrine treatment only), and then each year during a 4-year follow-up period, for both arms.

A 4-year mortality score including items depicting functional status, nutritional status and comorbidities, three key issues in elderly, will be systematically calculated.

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

The EORTC QLQ-ELD15, a validated HRQOL questionnaire for cancer patients aged greater than or equal to 70 years, is intended to supplement the QLQ-C30.

The QLQ-ELD15 contains 15 items incorporating five scales to assess mobility, family support, worries about future, autonomy and maintaining purpose, and burden of illness. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. High scores indicate poor mobility, good family support, less worried about the future, poor autonomy and maintaining purpose, and high burden of illness.

The prognostic signature of the GG test will be evaluated in an elderly population by comparison to standardized routine histopathological criteria and to the results obtained in the general non elderly population. In the whole cohort (n=2000) results of the GG will be compared to routine histopathological characteristics (pN, histological grade, mitotic count, Ki67 index, determination of Elston and Ellis histological grade) as determined locally or centrally for assessment of patient prognosis.

In parallel with efficacy analysis, measured by an objective clinical result indicator of state of health, such as the number of year gained (overall survival), costs for the two treatment strategies (endocrine treatment only or endocrine treatment and chemotherapy) in adjuvant systematic treatment will be also estimated. This study should provide information for decision-makers about the incremental efficacy obtained in relation to the incremental cost.

Spots Global Cancer Trial Database for chemotherapy then hormonotherapy