Randomised trial of letrozole plus usual care versus usual care without letrozole to prevent new breast cancer events in postmenopausal women who have completed a minimum of 4 years of adjuvant endocrine therapy for early, hormone responsive breast cancer more than 1 year previous, and who are disease-free at trial entry (ANZ 0501 LATER)

Funding

Self funded/Unfunded,Novartis Pharmaceuticals Australia Pty Ltd

Scientific enquiries

Prof John F Forbes

Brief Summary

The major concern for women on long term follow up after breast cancer has been treated, is fear of the reoccurrence of disease. This study will test a new strategy to prevent disease reocurrence and death due to breast cancer. The purpose of the study is to find out whether later re-treatment of participants with adjuvant letrozole therapy can prevent or delay new breast cancers from reoccurring in postmenopausal women previously treated with adjuvant endocrine therapy

Key Inclusion Criteria

Patients must be postmenopausal, which is defined as meeting one or more of the following criteria: prior bilateral oophorectomy aged 60 years or more; if the patient has any clinical evidence of ovarian function, FSH levels must be assessed and be in the postmenopausal range. aged under 60 years: a) with a uterus and amenorrhoea for at least 12 months prior to trial entry (see Note 2) b) with amenorrhoea for less than 12 months prior to trial entry and an follicle stimulating hormone (FSH) leve .... Patients must be postmenopausal, which is defined as meeting one or more of the following criteria: prior bilateral oophorectomy aged 60 years or more; if the patient has any clinical evidence of ovarian function, FSH levels must be assessed and be in the postmenopausal range. aged under 60 years: a) with a uterus and amenorrhoea for at least 12 months prior to trial entry (see Note 2) b) with amenorrhoea for less than 12 months prior to trial entry and an follicle stimulating hormone (FSH) level in the postmenopausal range c) without a uterus and an FSH level in the postmenopausal range Note 1: Patients who have taken hormone replacement therapy (HRT) must have ceased HRT at least 8 weeks prior to randomisation and be free of per vagina bleeding for this time. FSH levels must be assessed after the completion of this 8 week interval. Note 2: Women aged under 60 years who have developed amenorrhoea after undergoing endometrial ablation or been rendered amenorrhoeic by adjuvant chemotherapy are not eligible unless FSH is in the postmenopausal range. Patients must have had previous completely resected hormone responsive (oestrogen receptor (ER) and/or Progesterone receptor (PgR) positive) invasive breast cancer determined by immunohistochemistry. Patients must have completed a minimum of 4 years of adjuvant endocrine therapy (Selective oestrogen receptor modulator (SERM) / Aromatase Inhibitor (AI) / Other - including ovarian function suppression, combination or sequential Adjuvant endocrine therapy (AET), blinded trial AET) at least 12 months previously. It is anticipated that women who have completed AET much longer than 1 year ago will be entered onto the trial; the only limiting factor being that women are in good health and suitable for prolonged follow-up. Patients who have had bilateral breast cancer are eligible provided that they have had at least one hormone responsive tumour. All treatment for hormone non-responsive tumours must have been completed and these tumours must have been diagnosed at least 5 years ago. Currently free of breast cancer. Adequate bone marrow function, renal function and hepatic function within 6 months prior to randomisation. Additional investigations including chest x-ray, computed tomography scan (CT), magnetic imaging scan (MRI) or positron emission tomograpy (PET) scan should be carried out as medically indicated to rule out metastatic disease. Bilateral mammogram performed within 12 months prior to randomisation unless the initial surgery was a total mastectomy in which case a unilateral mammogram may be performed. A mammogram is not required if the patient has had a bilateral mastectomy. Bone health must be evaluated prior to randomisation and be deemed clinically as adequate. A Bone Mineral Density Scan (DXA Scan) of hip, femoral neck, or lumbar spine must be performed within 12 months prior to randomisation and the T-score must be greater than or equal to minus 4.0. (Note: Spinal x-rays to assess for low trauma vertebral fractures are also strongly recommended). Note: If a woman with osteoporosis (T-score between minus 2.5 and minus 4.0) and/or with low trauma vertebral fractures wishes to join the trial she must receive appropriate care for osteoporosis under the direction of her general practitioner or treating clinician. Must be geographically accessible for follow-up. Life expectancy of at least 10 years. Ability to fully understand, sign and date the written informed consent document, and agree to the collection and use of breast cancer tumour specimens where available as specified in the protocol and Participant Information Sheet and Consent Form.
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Key Exclusion Criteria

Premenopausal patients. Patients previously diagnosed with only hormone non-responsive early breast cancer. Patients with any local recurrence or distant metastases of breast cancer. Any suspicious manifestation requires appropriate investigation to exclude metastases. Patients with non-malignant systemic diseases which would prevent prolonged followup, or in the opinion of the investigator, would place the woman at unusual risk or confound assessment for breast cancer events and the results of .... Premenopausal patients. Patients previously diagnosed with only hormone non-responsive early breast cancer. Patients with any local recurrence or distant metastases of breast cancer. Any suspicious manifestation requires appropriate investigation to exclude metastases. Patients with non-malignant systemic diseases which would prevent prolonged followup, or in the opinion of the investigator, would place the woman at unusual risk or confound assessment for breast cancer events and the results of the trial. Any previous non-breast cancer within the last 5 years, except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumours curatively treated more than 5 years ago with no evidence of recurrence. Intention to continue or commence systemic oestrogen and/or progesterone based Hormone Replacement Therapy (HRT). Osteoporotic with a T-score less than or equal to minus 4.0 within 12 months prior to randomisation. Patients with diagnosed hypercholesterolaemia, unless currently being treated with cholesterol lowering drugs and/or therapeutic lifestyle changes under the care of their medical practitioner. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Letrozole. Any co-existing medical or psychiatric condition that would limit compliance with trial requirements. Treatment with non-approved or experimental drug on a different clinical trial during the three months before randomisation. Prior treatment on a designated trial for breast cancer if permission has not been obtained from the sponsors of the original trial for the patient to participate in LATER.
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