Preparations for hormone therapy for breast cancer and their effectiveness

In breast cancer, further extensive spread of the disease often occurs due to micrometastases not found at the time of diagnosis. Therefore, after treatment aimed at eliminating a local tumor, more and more attention is paid to subsequent adjuvant systemic therapy.

The goal of adjuvant therapy is to maximize the elimination of all potential tumor foci until their clinical manifestation. In animal experiments, it has been shown that small metastases are more susceptible to chemotherapy drugs. Although most of these experiments were carried out on a small number of animals, which reduces the reliability of the findings, recent clinical studies have demonstrated the effectiveness of adjuvant therapy, which also manifests itself during long periods of patient follow-up.

As soon as the fact of regression of a common tumor after removal of the ovaries was established, several studies were performed to determine the possibility of using oophorectomy as a method of adjuvant therapy after mastectomy. Currently, the efficacy of this method has been convincingly demonstrated in observations on randomized groups of patients with ER-positive tumors.

In 1998, the results of all prospectively randomized observations on groups of patients who were prescribed tamoxifen, as well as a course of adjuvant therapy, were published. The long-term beneficial effect on the survival of patients who received tamoxifen for at least 2 years after the end of the primary treatment was fully confirmed.

This effect was observed after 15 years of observation. It manifested itself in both patients with localized tumors, and in cases of extensive tumor process affecting the lymph nodes. After 10 years of observation, a higher effect of tamoxifen was observed than after a 5-year period, which in itself was quite unexpected. It has now become clear that it takes at least 5 years to manifest the maximum beneficial effect of the drug.

Such an additional beneficial effect of the drug as a decrease in the level of cholesterol in the blood, which is also accompanied by a decrease in the mortality of patients from myocardial infarction, is noted. Tamoxifen prevents the decalcification of bones, which is observed in postmenopause. However, when taking the drug among women, there was an increase in the number of cases of endometrial carcinoma, and, much less often, uterine sarcoma. A recent and very important study by Fisher and co-workers stated that the beneficial effect after treatment with tamoxifen has been maintained for at least 15 years.

As the authors note, “the point of view that tamoxifen or chemotherapy should be used only according to the indications of age seems too limited.” In each individual case, it is necessary to make a difficult decision regarding the “best choice” of the method of adjuvant therapy.

Several large studies have now been made that compare the effectiveness of aromatase inhibitors and tamoxifen in the treatment of postmenopausal cancer. In the most large-scale study of ATAS, anastrozole (1 mg per day, orally) was shown to be more effective and less toxic than tamoxifen.

At the same time, the maximum effect of the drug when used as an adjuvant means develops earlier than 5 years after administration. There were 575 patients in the group receiving anastrozole, and 651 patients in the group treated with tamoxifen. The increase in relapse-free survival in the group treated with anastrozole, compared with the group receiving tamoxifen, was 3.3%, and this difference was maintained for 6 years. Moreover, patients tolerated anastrozole much better.

They significantly reduced the risk of thromboembolic complications and decreased gynecological symptoms (vaginal discharge and bleeding). In 17 out of 3125 patients who were treated with tamoxifen, endometrial carcinoma subsequently developed, while in the same size group receiving anastrozole, it was noted in only 5 patients. Another study demonstrated that prescribing an aromatase inhibitor, letrozole, for another 5 years after the end of the standard 5-year regimen of tamoxifen treatment leads to an additional reduction in the risk of tumor recurrence.

The steroid inhibitor aromatase, exemestane, also has a beneficial effect when administered orally instead of tamoxifen in the middle of the treatment period in the standard 5-year regimen. The administration of goserelin, which blocks the function of the ovaries, to patients with ER-positive tumors in the premenopause period was as effective as CMF chemotherapy. According to international recommendations for the treatment of breast cancer, the administration of goserelin can be used as an independent method of treatment, and in combination with chemotherapy.

For patients with hormone-positive tumors in premenopause, treatment with the goserelin antagonist, GnHRH, is just as effective as standard chemotherapy, but the inherent toxic effects do not manifest themselves. This drug was the first to be able to sufficiently fully and reversibly suppress the effect of estrogen, and cause a temporary development of the postmenopause state in a woman’s body.

When administered jointly with tamoxifen, its effect is enhanced, which is not observed in the case of postmenopausal tumors, in which the administration of anastasol-tamoxifen pair is no more effective than the administration of tamoxifen alone.

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