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.
OBJECTIVE
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.


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 > or =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).


CONCLUSIONS
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.
Rosendahl
Mikkel
M
The Fertility Clinic and Laboratory of Reproductive Biology, Copenhagen University Hospital - Rigshospitalet, Denmark. mikro@dadlnet.dk
Ahlgren
Johan
J
Andersen
Jørn
J
Bergh
Jonas
J
Blomquist
Carl
C
Lidbrink
Elisabet
E
Lindman
Henrik
H
Mouridsen
Henning
H
Bjerre
Karsten
K
Andersson
Michael
M
D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000568:Amenorrhea / Q000139:chemically induced* / Q000453:epidemiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced*; D008597:Menstrual Cycle / Q000187:drug effects; D008875:Middle Aged; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced
D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil