Abril - 2017

arros

-O

liveira

376

ssoc

ras

2017; 63(4):371-378

embolism), and effectiveness of AIs in breast cancer treat-

ment has been demonstrated. Therefore, there has been

great interest in the use of AIs for breast cancer chemo-

prevention. However, in the configuration of the chemo-

prevention programs, AIs have not yet been approved.

40,41

In recent years, two clinical trials have reported their main

results on cancer prevention using AIs: the Mammary

Prevention 3 Study (MAP3) and the International Breast

Cancer Intervention Study-II (IBIS-II).

The MAP3 trial involved the randomization of 4,500

postmenopausal women at risk of developing breast can-

cer, who were allocated into two groups, exemestane and

placebo, for 5 years. After a mean 35 month follow-up pe-

riod, a 65% reduction in invasive breast cancers was observed

in women using exemestane and no effect was observed in

ER-negative women. No significant differences in side ef-

fects were found between groups, suggesting a good risk-

-benefit profile. However, the limitation of this study was

the short follow-up period, which was only 35 months. Due

to this, the MAP3 trial does not allow for any conclusions

on the long term safety and efficacy of this drug.

The aim of the IBIS-II trial was to evaluate the effi-

cacy and safety of anastrozole for breast cancer prevention

in high-risk postmenopausal women. The IBIS-II assessed

only anastrozole versus placebo due to more effective

action of anastrozole in breast cancer chemoprevention

of postmenopausal women compared to tamoxifen.

For

that trial, postmenopausal women (n=3,864) were ran-

domized into a group using 1 mg of anastrozole daily or

a group treated with a placebo. After a median follow-up

period of 5 years, it could be observed that anastrozole

significantly reduced the diagnosis of invasive breast

cancer, and ductal carcinoma in situ, similarly to the

results reported in the MAP3 trial. Also similarly to the

MAP3 trial, it was found that anastrozole had no effect

on ER-negative women. The strengths of this study were

the large number of cancers reported and the mean follow-

-up period of 5 years. All women in the study continue the

long-term follow-up in a blinded fashion. This is impor-

tant because the long-term global efficacy of anastrozole

and other AIs has not yet been established for healthy

postmenopausal women who are at increased risk of

developing breast cancer.

The decline in invasive breast carcinoma observed with

the use of exemestane and anastrozole was greater than

that observed with TAM or any other SERM, and these

results indicate that both drugs are attractive options for

the prevention of breast cancer in postmenopausal women

at increased risk of developing the disease.

nimal models

The chemopreventive effects of anastrozole have also been

investigated in animal models. Significant improvement in

tumor supression was observed after induction of premeno-

pausal breast carcinogenesis in rats. The incidence of tumor

supression was 40% with the use of a dose of 0.5 mg/kg of

anastrozole. In addition, there were no adverse effects on

the genital system, lipid and bone metabolism of the rats.

Nevertheless, an increase in body weight was observed.

A similar study evaluated the side effects of anastro-

zole as a chemopreventive agent in the induction of pre-

menopausal breast carcinogenesis in rats. In rats given a

dose of 0.5 mg/kg of anastrozole, there were no macro-

scopic alterations in the uterus and vagina, histological

exam showed no atrophic changes in the endometrium

and vaginal epithelium, although the myometrium was

significantly thicker. Changes in lipid metabolism and

serum levels of sex hormones were not observed. How-

ever, a significant increase in cortical bone thickness and

body weight was found.

onclusion

Anastrozole is one of the third-generation AIs, a highly

competitive and selective inhibitor of aromatase, which is

the enzyme responsible for the conversion of androgens

into estrogen in postmenopausal women. Large studies

have demonstrated the effective use of a daily dose of 1 mg

of anastrozole in these women. Anastrozole has a sig-

nificant action in metastatic disease, as well as in the

adjuvant treatment and chemoprevention of breast can-

cer. However, recent studies have shown that interindi-

vidual variability may affect pharmacodynamic and phar-

macokinetic properties while using this dose in some

women. Anastrozole may be used as an option for efficient

and tolerable endocrine treatment in all stages of cancer

in the majority of postmenopausal women.

esumo

Uso do anastrozol na quimioprevenção e no tratamento

do câncer de mama: uma revisão da literatura

Os inibidores de aromatase têm emergido como uma

endocrinoterapia alternativa para o tratamento de câncer

de mama sensível a hormônios em mulheres pós-meno-

páusicas. A utilização de inibidores de terceira geração,

representados por exemestano, letrozol e anastrozol, é

atualmente indicada. Anastrozol é um composto não

esteroide e um inibidor potente e seletivo da enzima aro-