Genetic Testing or Clinical Assessment in Determining the Need for Chemotherapy in Women With Breast Cancer That Involves No More Than 3 Lymph Nodes

• Status: Active, not recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: Female

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving chemotherapy and hormone therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether genetic testing is more effective than clinical assessment in determining the need for chemotherapy in treating breast cancer.

PURPOSE: This randomized phase III trial is studying genetic testing to see how well it works compared with clinical assessment in determining the need for chemotherapy in women with breast cancer that is either node-negative or involves no more than 3 lymph nodes.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Agendia; Breast International Group; Novartis; Roche Pharma AG; Sanofi
• Treatments: Capecitabine; Docetaxel

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer meeting the following criteria:

• T1, T2, or operable T3 disease

• Zero to three positive lymph nodes and no distant metastases

• Unilateral tumor

• Multifocal tumors are allowed provided that they have identical histology

• Ductal carcinoma in situ or lobular carcinoma in situ allowed

• Operable disease

• Must have undergone breast-conserving surgery or mastectomy with either a sentinel node procedure or full axillary clearance

• Radiotherapy is mandatory in the case of breast-conserving surgery

• Unresectable positive deep margins and will receive adjuvant radiotherapy provided that all other margins negative allowed

• Patients eligible for inclusion in the chemotherapy randomization must meet one of the following criteria:

• High-risk of recurrence according to both the clinical-pathological criteria and the 70-gene signature

• High risk of recurrence according to the clinical-pathological criteria and low-risk of recurrence according to the 70-gene signature and are randomized to use the clinical-pathological criteria for chemotherapy decision

• Low-risk of recurrence according to the clinical-pathological criteria and high-risk of recurrence according to the 70-gene signature and are randomized to use the 70-gene signature for chemotherapy decision

• Patients eligible for inclusion in the endocrine therapy randomization must meet all of the following criteria:

• Endocrine-responsive disease

• Hormone receptor-positive disease (estrogen receptor-positive, progesterone receptor-positive, or both)

PATIENT CHARACTERISTICS:

• Female

• WHO performance status 0-1

• Neutrophil count > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Creatinine clearance at least 50 mL/min OR creatinine up to 1.5 times upper limit of normal (ULN)

• ALT and AST up to 2.5 times ULN

• Alkaline phosphatase up to 2.5 times ULN

• Bilirubin up to 2.0 times ULN

• Normal echocardiogram (ECHO) compatible with chemotherapy treatment

• No serious cardiac illness or medical condition including, but not limited to, any of the following:

• History of documented congestive heart failure

• High-risk uncontrolled arrhythmias

• Angina pectoris requiring antianginal medication

• Clinically significant valvular heart disease

• Evidence of transmural infarction on ECG

• Poorly controlled hypertension (e.g., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)

• Symptomatic coronary artery disease or a myocardial infarction within the past 12 months

• Other risk factors that contraindicate the use of anthracycline-based chemotherapy

• No serious uncontrolled infection or other serious uncontrolled disease

• No other cancer within the past 5 years except for adequately treated carcinoma in situ of the cervix, nonmelanoma skin cancer, lobular or ductal carcinoma in situ of the breast, or any invasive cancer (other than breast cancer)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• No psychological, familial, sociological, or geographical condition that would preclude study treatment

• No psychiatric disability

• No history of uncontrolled seizures or CNS disorders

• Patients eligible for inclusion in the chemotherapy randomization must meet all of the following additional criteria:

• LVEF normal by ECHO or MUGA

• No prior severe hypersensitivity reaction to drugs formulated with polysorbate 80

• Must have physical integrity of the upper gastrointestinal tract

• Able to swallow tablets

• No malabsorption syndrome

• No prior thromboembolic disorder, deep vein thrombosis, or pulmonary emboli (for patients eligible for inclusion in the endocrine therapy randomization)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior neoadjuvant chemotherapy, neoadjuvant endocrine therapy, or radiotherapy for primary breast cancer

• No participation in another investigational drug study within the past 4 weeks

• No systemic hormone replacement therapy (with or without progestins) for more than 3 months in duration

• Patients eligible for inclusion in the chemotherapy randomization must meet all of the following additional criteria:

• Interval between definitive surgery and start of chemotherapy 8-18 weeks

• No prior organ allografts requiring immunosuppressive therapy

• No concurrent sorivudine or chemically related analogues, such as brivudine

• Patients eligible for inclusion in the endocrine therapy randomization must meet all of the following additional criteria:

• No prior high-dose systemic corticosteroids (except as antiemetic treatment), immunotherapy, or biological response modifiers (e.g., interferon)

• No prior adjuvant antiestrogen therapy for > 1 month immediately after surgery, radiotherapy, and/or chemotherapy

• No hormone replacement therapy within the past 4 weeks

• No antiestrogens (e.g., tamoxifen or raloxifen) as chemoprevention or osteoporosis treatment for breast cancer within the past 18 months

• No concurrent primary prophylaxis with filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim

• No other concurrent treatment during endocrine therapy, including the following:

• Anticancer therapy (anti-estrogens, aromatase inhibitors, chemotherapy)

• Investigational agents

• Raloxifene or other selective estrogen-receptor modulators

• Hormonal contraceptives (including depot injections and implants)

• Intrauterine devices, including progesterone-coated, allowed

• Oral or transdermal hormonal treatments, including estrogen, progesterone, androgen, or aromatase inhibitor

• Local vaginal (topical) estrogens with minimal systemic absorption allowed for severe vaginal dryness/dyspareunia

• Concurrent bisphosphonates allowed