Aromatase Inhibitors: A New Reality for the Adjuvant Endocrine Treatment of Early-Stage Breast Cancer in Postmenopausal Women
Pp. 99-130 (32)
Colozza Mariantonietta, Minenza Elisa, Nunzi Martina, Sabatini Silvia, Dinh Phuong, Califano Raffaele and De Azambuja Evandro
Tamoxifen, a selective estrogen receptor modulator (SERM), has been used
for many decades as the “gold standard” adjuvant treatment for patients with hormonereceptor-
positive early breast cancer. This drug, when administered for 5 years, reduces
the risk for recurrence, contralateral breast cancer (BC) and death. These benefits have
been observed up to 15 years and are independent of the patient’s age, menopausal
status, nodal status, hormonal receptor status, and the use of adjuvant chemotherapy.
The optimal duration of tamoxifen in the adjuvant setting has not been established yet,
but it has been demonstrated that 5 years are better than shorter treatment while it is still
unclear if a prolongation of the treatment for more than 5 years is worthwhile.
Tamoxifen is usually well-tolerated, but important adverse events such as endometrial
cancer, cerebrovascular accidents and thromboembolic events can occur, and the
increase in absolute risk of these adverse events appears to be age-correlated.
In the last decade, third generation aromatase inhibitors (AIs), either steroidal
(exemestane) or non-steroidal (anastrozole, letrozole), have shown to be an effective
alternative to tamoxifen in postmenopausal patients with BC regardless of its stage.
These agents act by blocking the aromatase enzyme which converts androgens into
estrogens. Trials comparing AIs to tamoxifen in postmenopausal women with metastatic
disease have shown a superiority of AIs over tamoxifen and a more favourable safety
profile. In the adjuvant setting, AIs have been shown to be more effective than
tamoxifen given for 5 years either in the up-front administration or after 2-3 years (early
switch). Two randomised trials which have evaluated the two strategies of AIs
administration have shown superimposable results in terms of efficacy with AIs given
up-front or in sequence to tamoxifen. AIs seem to give benefits in comparison to
placebo if given after 5 years (late switch) of tamoxifen. At the moment, therefore, the
treatment decision should be based on individual factors such as risk of relapse,
absolute benefit, and comorbidities.
Adjuvant endocrine therapy, aromatase inhibitors, breast cancer,
S.C. Oncologia Medica, Azienda Ospedaliera, Via Tristano di Joannuccio 1, 05100 Terni, Italy.