Concomitant and Sequential Radiohormonotherapy in Adjuvant Breast Cancer

A Phase II Randomized Study to Compare Skin Late Toxicities of Concomitant Letrozole-Radiotherapy and Radiotherapy Followed by Letrozole as Adjuvant Therapy for Postmenopausal Women With Receptor (ER and/or PgR) Positive Tumors

This trial will compare grade 2 or greater late skin toxicities of concomitant letrozole-radiotherapy and radiotherapy followed by letrozole as adjuvant therapy for postmenopausal women with receptor (estrogen receptor [ER] and/or progesterone receptor [PgR]) positive tumors. Each drug will be prescribed for 5 years.

This trial is an open-label randomized multicenter phase II study.

A ratio of 1 to 1 will be used for the randomization process between the two arms:

• Arm A : Letrozole 2.5 mg daily for 5 years started three weeks before the first day of adjuvant radiotherapy.
• Arm B : Letrozole 2.5 mg daily for 5 years started three weeks after the last day of adjuvant radiotherapy.

All patients will be followed every 3 months for toxicities, disease status and for survival until death.

Inclusion Criteria:

• Compliant postmenopausal women
• Conservative breast cancer surgery
• Extension evaluation of disease will be proven negative
• Patients with tumor negative margins
• Patients will be classified as T1, T2, T3; Sentinel node negative, N0, N1 or N2; M0.
• Receptor positive tumors (ER and/or PgR = 10 fmol/mg cytosol protein; or = 10% of the tumor cells positive by immunocytochemical evaluation).
• Adequate marrow function (polynuclear neutrophils >= 1200.10^9/l, platelets >= 100.10^9/l, and hemoglobin >= 10 g/dl).
• Hepatic function (bilirubin >= 30 µmol/l, ALT (SGPT) or AST (SGOT) >= 1.5 x upper limit of the institution) and cholesterol level <2 x upper limit of the institution.
• Must be geographically accessible for follow-up.
• Written and dated informed consent

Exclusion Criteria:

• Patients with distant metastases.
• Bilateral breast cancer (concomitant or prior) except in situ lesion, either ductal or lobular, of the contralateral breast.
• Patients staged T4 or N3 or treated by not conservative surgery (radical mastectomy).
• Patients with neoadjuvant chemotherapy or hormonal therapy.
• Patients with previous or concomitant other (not breast cancer) malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least five years.
• Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.
• Patients treated with systemic investigational drugs within the past 30 days.
• Breast cancer chemoprevention with anti-estrogens
• Hormone replacement therapy (HRT) not stopped at least 4 weeks before randomization
• Patients known to be HIV positive (no specific tests are required to determine the eligibility).