The risk of amenorrhoea after adjuvant chemotherapy for early stage breast cancer is related to inter-individual variations in chemotherapy-induced leukocyte nadir in young patients: Data from the randomised SBG 2000-1 study

Abstract

Study aim Amenorrhoea is a common side-effect to chemotherapy of premenopausal women. We examine the association between chemotherapy-induced leucopaenia and the development of amenorrhoea in premenopausal women with breast cancer. Materials and methods In a multi-centre, randomised, controlled study, 1016 premenopausal women received seven series of FEC (F: fluorouracil, E: epirubicin and C: cyclophosphamide) for early stage breast cancer. In the first series, all patients received standard dose (F: 600 mg/m 2, E: 60 mg/m 2 and C: 600 mg/m 2). Patients with leukocyte nadir 1.0–1.9 × 10 9/l continued with standard dose for the remaining six series (STANDARD REGISTERED, n = 279). Patients with leukocyte nadir ⩾2 × 10 9/l were randomised to standard (STANDARD RANDOMISED, n = 373) or increased (TAILORED, n = 364) dose of E and C. After each series, leukocyte nadir was evaluated. Absent bleeding after the 5th–7th series of FEC was interpreted as amenorrhoea. Results The risk of amenorrhoea increased with age. In age-stratified analysis of the STANDARD groups (equal dose, different initial leukocyte nadir) low leukocyte nadir was associated with amenorrhoea for patients in the age-group 25–39 years ( P = 0.010). In age-stratified analysis in the randomised groups (different doses, same initial leukocyte nadir) a dose related increased risk of amenorrhoea was found for age-groups 25–39 (RR: 1.15, 95% confidence interval (CI): 1.06–1.24) and 40–44 years (RR:1.21, 95% CI: 1.001–1.47). Conclusion Age is the most important risk factor of amenorrhoea after FEC chemotherapy. However, for younger patients, lower leukocyte nadir in response to STANDARD FEC treatment or increased doses of C and E were associated with increased risk of amenorrhoea.