Side effects of adjuvant endocrine treatment in premenopausal breast cancer patients: a prospective randomized study.
OBJECTIVE
To compare the effect of adjuvant endocrine therapies with and without chemotherapy on physical symptoms, anxiety, and depressive symptoms in premenopausal women with breast cancer in a randomized clinical trial (the Zoladex in Premenopausal Patients trial).


METHODS
The patients were randomly assigned to goserelin, goserelin plus tamoxifen, tamoxifen alone, or no endocrine therapy. The duration of the endocrine treatment was 2 years. The groups were observed for 3 years after primary treatment (ie, during 2 years of active treatment as well as 1 year after cessation of the adjuvant endocrine therapy). All patients with node-positive disease received adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF), which was given concurrently with the endocrine treatment.


RESULTS
Patients treated with CMF typically reported higher levels of physical symptoms than did patients who did not receive CMF. It was only among patients who did not receive chemotherapy that the endocrine treatment had differential effects. Goserelin was most burdensome and resulted in similar symptom levels as those of CMF, whereas the side effects of tamoxifen alone were milder. After cessation of the endocrine treatment, the side effects diminished in patients who had not received CMF, whereas patients treated with CMF reported ongoing problems at the 3-year follow-up. In contrast, anxiety and depressive symptoms were not significantly affected by endocrine treatment or chemotherapy during the 3 years of assessment.


CONCLUSIONS
Goserelin and tamoxifen resulted in menopausal symptoms, but these symptoms were reversible. However, women treated with CMF experienced physical symptoms throughout the whole study period.
Nystedt
Marianne
M
Unit of Psychosocial Oncology and Rehabilitation, Karolinska Hospital, S-171 76, Stockholm, Sweden. marianne.nystedt@home.se
Berglund
Gunilla
G
Bolund
Christina
C
Fornander
Tommy
T
Rutqvist
Lars Erik
LE
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001007:Anxiety; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000523:psychology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide; D003863:Depression; D005260:Female; D005472:Fluorouracil; D017273:Goserelin / Q000009:adverse effects* / Q000494:pharmacology*; D006304:Health Status; D006801:Humans; D008727:Methotrexate; D008875:Middle Aged; D017697:Premenopause; D012720:Severity of Illness Index; D013629:Tamoxifen / Q000009:adverse effects* / Q000494:pharmacology*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate