Investigation on the Duration of Extended Adjuvant Letrozole treatment.

1. Postmenopausal at the time of randomization;

2. Histologically proven invasive breast cancer (stage I, II, or III) adequately treated at the time of diagnosis;

3. ER and/or PgR positive breast cancer;

4. Completed 5 year (± 3 months) adjuvant endocrine therapy with either tamoxifen for 5 years, aromatase inhibitors for 5 years or a sequence of both (provided that tamoxifen was given upfront for 2-3 years);

5. No evidence of breast cancer recurrence including contralateral breast cancer at the time of randomization;

6. WHO performance status 0, or 1;

7. Adjuvant endocrine treatment completed for no longer than 2 years (with a tolerance window of 3 months);

8. Accessible for follow-up for the duration of the trial;

9. Written informed consent.

1. ER and PgR negative or unknown primary tumors;

2. Evidence of previous or current localized or distant breast cancer recurrence;

3. Bilateral breast cancer and/or (preventive) bilateral mastectomy;

4. Untreated hyperlipidemia (total cholesterol ≥ 7.75 mmol/L, triglycerides ≥ 2.5 x ULN);

5. Concurrent use of other aromatase inhibitors;

6. Concurrent chemotherapy;

7. Any use of HRT or SERMS. Patients on HRT and willing to participate in the trial will have to discontinue HRT 4 weeks prior to randomization. Topical estrogens are discouraged during the trial;

8. Previous or concomitant malignancy within the past 5 years (except adequately treated basal or squamous cell carcinoma of the skin or CIS of the cervix). Patients with a malignancy in their history more than 5 years ago must be disease free at least for 5 years. Patients with a history of breast cancer, other than the breast cancer under study are always excluded;

9. Other non-malignant systemic diseases including uncontrolled infections, uncontrolled DM-II, uncontrolled thyroid dysfunction, cardiovascular, renal, hepatic, and lung diseases, which would prevent prolonged follow-up. Patients with previous history of thrombosis or thromboembolism can be included only if medically suitable;

10. Patients with a known history of HIV;

11. Severe concomitant physical or psychological diseases that might impair compliance or assessment of drug/patient safety, e.g. clinically significant ascites, cardiac failure, NYHA III or IV, clinically relevant pathologic findings in ECG;

12. Uncontrolled seizure disorders associated with falls;

13. Patients treated with systemic investigational drug(s) and/or device(s) within the past 30 days or topical investigational drugs within the past 7 days;

14. History of non-compliance to medical treatment and patients considered potentially unreliable;

15. Mental illness that precludes the patient from giving informed consent.