Uterine and quality of life changes in postmenopausal women with an asymptomatic tamoxifen-thickened endometrium randomized to continuation of tamoxifen or switching to anastrozole.
OBJECTIVE
Before the knowledge that 5 years of adjuvant tamoxifen is less efficacious than 2 to 3 years of tamoxifen followed by 2 to 3 years of anastrozole/exemestane, we designed a multicenter double-blind randomized controlled trial in women taking tamoxifen with a thickened endometrium to compare uterine and quality-of-life parameters between those switching to anastrozole and those continuing tamoxifen.


METHODS
Asymptomatic postmenopausal women who took adjuvant tamoxifen for 2 to 3 years for operable breast cancer with a double endometrial thickness greater than 7 mm were randomized to 20 mg tamoxifen or 1 mg anastrozole for the remaining duration, totaling 5 years. Tablets were unrecognizable for drug assignment. The primary endpoints were the differences in double endometrial thickness and uterine volume after 1 year. Uterine and quality-of-life data were analyzed using regression methods, and missing values were handled using multiple imputation.


RESULTS
Seventy-two women (median age, 60 y) were randomized in five hospitals. Relative to women continuing tamoxifen, women switching to anastrozole experienced a decrease of 53% (95% CI, 41%-63%) in double endometrial thickness and a decrease of 51% (95% CI, 39%-60%) in uterine volume. Vaginal dryness (b = 0.064; 95% CI, 0.016-0.112) and sexual problems (b = 0.054; 95% CI, 0.007-0.102) increased in women taking anastrozole compared with women taking tamoxifen. Treatment arms did not differ regarding withdrawal rate and the experience of (serious) adverse events.


CONCLUSIONS
Despite premature trial closure, our data provided valuable insights. Switching to anastrozole strongly decreased the endometrial thickness and uterine volume but increased sexual disturbances. Safe and effective interventions are needed to alleviate sexual dysfunction.
Van Calster
Ben
B
Department of Electrical Engineering (ESAT-SCD), Katholieke Universiteit Leuven, Leuven, Belgium. ben.vancalster@esat.kuleuven.be
Van Ginderachter
Johan
J
Vlasselaer
Jos
J
Van de Putte
Gregg
G
Berteloot
Patrick
P
Timmerman
Dirk
D
Depypere
Herman
H
Blomme
Chantal
C
Vlaemynck
Geert
G
De Jonge
Eric
E
Van den Broecke
Rudy
R
Vergote
Ignace
I
Amant
Frédéric
F
Van Huffel
Sabine
S
Neven
Patrick
P
D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause / Q000187:drug effects*; D011788:Quality of Life; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014599:Uterus / Q000187:drug effects*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole