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
2009 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 45, no 18, 3198-3204 p.Article in journal (Refereed) Published
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 x 10(9)/l continued with standard dose for the remaining six series (STANDARD(REGISTERED), n = 279). Patients with leukocyte nadir >= 2 x 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. (C) 2009 Elsevier Ltd. All rights reserved.
Place, publisher, year, edition, pages
2009. Vol. 45, no 18, 3198-3204 p.
Breast cancer, Amenorrhoea, Ovarian failure, Menopause
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-138123DOI: 10.1016/j.ejca.2009.09.019ISI: 000273143800018OAI: oai:DiVA.org:uu-138123DiVA: diva2:378881