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

Study aimAmenorrhoea 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 methodsIn 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/m2, E: 60 mg/m2 and C: 600 mg/m2). Patients with leukocyte nadir 1.0–1.9 × 109/l continued with standard dose for the remaining six series (STANDARDREGISTERED, n = 279). Patients with leukocyte nadir ⩾2 × 109/l were randomised to standard (STANDARDRANDOMISED, 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.ResultsThe 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).ConclusionAge 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.