Certain tissues of the female reproductive tract, which are subject to the trophic action of hormones, exhibit a high frequency of neoplasia. Cancer of the breast, the second most common form of cancer in American women, and the rarer endometrial cancer in women, are often responsive to treatments with estrogens or pro-gestins. The toxicity of these hormonal treatments com-pared with standard cancer chemotherapy is low.
Early breast cancer is usually treated by surgery and lo-cal irradiation. Hormonal therapy is reserved for pa-tients with advanced metastatic breast cancer. Breast cancer occurs in both premenopausal and postmeno- pausal women. Approximately one-third of patients have a complete or partial remission with a mean dura-tion of 9 to 12 months after hormonal therapy. Hor-monal therapy of advanced breast cancer is not cura-tive, but extended control of disease is possible by the use of different hormonal therapies sequentially.
Estrogen receptor–positive breast cancer in pre-menopausal and postmenopausal women responds equally to tamoxifen therapy . In addi-tion, daily tamoxifen administration for 5 years is a suc-cessful therapy for the prevention of breast cancer in the contralateral breast in women who have already had one episode of breast cancer.
Progestins have been used with some success in the treatment of breast cancer, and the response rate is ap-proximately the same as with tamoxifen. Most clinical experience has been obtained using oral megestrol ac-etate.
The successful response of breast cancers to tamox-ifen or progestin treatment depends on the presence of high-affinity receptors for estrogen, progesterone, or both. Fewer than 10% of mammary tumors that lack detectable ER levels will respond to hormonal thera-pies. Determination of hormone receptor levels in tumor samples is highly recommended before selecting a therapy.
Although estrone is a weak estrogen, breast tissue metabolizes estrone and estrone sulfate to estradiol, providing a trophic signal for tumor growth. The newest drug introduced for the hormonal control of breast can-cer is letrozole (Femara). It is a nonsteroidal aromatase inhibitor that dramatically reduces serum levels of estradiol, estrone, and estrone sulfate in postmeno-pausal women by blocking the conversion of adrenal androgens, androstenedione, and testosterone to es-trone and estradiol. The duration of remission in breast cancer patients treated with letrozole exceeds that of ta-moxifen, and the drug can be used even in tumors that have developed resistance to tamoxifen. Letrozole is orally active and is excreted primarily in the urine. The incidence of side effects is rare. It does not change serum corticosteroid, aldosterone, or thyroid hormone levels. Anastrozole (Arimidex) is another promising third-generation aromatase inhibitor.
Progesterone administration induces remissions in ap-proximately one-third of patients with metastatic en-dometrial cancer. The mean duration of response is 27 months. Almost 60% of endometrial adenocarcinomas contain progesterone receptors. Preliminary data show a correlation between progesterone receptor status and response rates in this disease. The mechanism of the ef-fect of progesterone on endometrial cancer is not known.