Choosing hormones for treating breast cancer metastasis

In most cases, examinations of patients with localized tumors, the doctor concludes that the disease is predominantly systemic in nature, and metastases will develop later. Detection of numerous metastases, often years after the mastectomy, as well as during long-term observation of patients confirms this conclusion.

According to the classical studies of Brinkley and Heybittl, the overall survival of patients with breast cancer 25 years after treatment is only 20%. Even among patients in whom mastectomy was done in a timely manner (“early” operable cases), the survival rate is only 30%.

Usually the appearance of metastases leads to death within three years, although in cases where treatment is effective, patients can live longer. The probability of tumor metastasis strongly depends on the degree of involvement of axillary lymph nodes in the pathological process, which is determined by histological analysis of samples taken during surgery.

There is a relationship between the number of affected axillary lymph nodes and the probability of spread of metastases. Since the first operation of therapeutic oophorectomy, performed by Bitson in 1896, it has become obvious that a change in the hormonal status of the organism in cases of a common tumor process in at least one third of the patients results in a symptomatic effect.

Various methods have been used: removal of the ovaries or their irradiation (sometimes called “creating artificial menopause”), treatment with estrogens, antiestrogens, and gonadotropin releasing hormone antagonists (for example, goserelin).

This hormone regulates the secretion of luteinizing hormone (LHRH). Anabolic steroids, glucocorticoids and progesterone were also used, adrenal or pituitary removal was performed, and aromatase inhibitors (anastrozole or letrozole) were prescribed. The standard approach is based on the patient’s menstrual status.

For most patients with metastatic tumors in premenopause and perimenopause, surgical removal of the ovaries or their irradiation is used. However, with the advent of gonadotropin-releasing hormone antagonists, these procedures have become less common.

Antagonists provide a persistent reduction in estrogen levels and cause the patient to experience menopause, which lasts for about two months from the start of goserelin. The drug is prescribed monthly in the form of intramuscular injections.

However, as an alternative, such a surgical method as laparoscopic removal of the ovaries again became popular. This is a fairly safe and simple operation, after which the patient remains in the hospital for one night.

It should be noted that before the operation, the patients are carefully selected according to the criterion of the hormonal sensitivity of the tumor, and for those who are not supposed to display the therapeutic effect, the operation is not performed.

Tamoxifen is widely used for patients with postmenopausal tumors, since it has virtually no side effects. The drug acts as an antiestrogen, but probably has a direct cytotoxic effect. For almost 20 years, tamoxifen has been used as a standard adjuvant therapy drug.

Tamoxifen is administered orally at a daily standard dose of 20 mg. It has a slow cumulative effect. Side effects are rare, but hot flashes, nausea, hypercalcemia, thrombocytopenia, fluid retention, and menstrual disorders may occur. After taking the drug, most patients gain 1-2 pounds in weight, and some note a deterioration of the skin, hair and nails.

A much more significant effect was obtained when hormone therapy was prescribed to patients with hormone-dependent tumors, while in the treatment of hormone-independent tumors, a favorable effect was observed only in rare cases. The prognosis for hormone-dependent and independent tumors is different. For patients with hormone-dependent tumors, a longer recurrence-free period and a higher survival rate are characteristic.

The joint determination of ER and PR indicators provides a more accurate prediction of the sensitivity of the tumor to hormone therapy than is possible with only ER. Patients with PR-positive tumors are also characterized by a longer painless period.

The effectiveness of hormonal therapy is strongly influenced by the nature of the spread of metastases. Bone metastases show some sensitivity to hormones, although after treatment, patients live on average about 12-15 months. Nevertheless, some patients with hormone-sensitive tumors and bone metastases live longer, sometimes for several years.

In most cases, in case of recurrence of a premenopausal tumor, goserin (or its analogs) or laparoscopic oophorectomy (or ovarian irradiation) is used. These measures are effective for hormone-sensitive tumors. For tumors in the postmenopausal period, tamoxifen is usually prescribed if patients have not previously received this drug as an adjuvant therapy agent.

In any case, it can be expected that the survival rate of patients will be at least 30%. Exogenous hormones are prescribed until the effect comes. In the future, hormonal therapy is continued only to those patients who have manifested the effect of primary treatment.

Proposed new anticancer drugs belonging to the group of aromatase inhibitors. They include anastrozole, which blocks the biosynthesis of estrogen precursors and their subsequent transformations in tissues.

Anastrozole is effective when taken orally. It is well tolerated by patients, as well as other related compounds, so that these drugs quickly took the place of tamoxifen, which was ineffective in treating patients with hormone-dependent tumors that develop during the period of menopause.

The recommended daily dose is 1 mg. If there is a relapse after the initial treatment, then other drugs are prescribed, for example, anabolic steroids, progestogens and glucocorticoids. Anabolic steroids are more effective in patients with postmenopausal tumors, and, apparently, they are especially necessary to apply in cases of detection of bone metastases.

A favorable effect is achieved in approximately 20% of patients, but virilization is a disadvantage of steroid use. Convenient for use is nandrolone decanoate (Deca-Durabolin), which is administered as an intramuscular injection at a dose of 50-100 mg every 3-4 weeks.

If hormone therapy has previously produced positive results, then progestogens can be used. Medroxyprogesterone acetate (MPA, Provera) is most commonly used, which is usually administered orally at a dose of 100 mg three times a day. However, its use is limited due to the development of a side effect – weight gain.

Another progesterone derivative, megestrol acetate (Megace), has the same efficacy. The choice of treatment for the first recurrence of a tumor is widely discussed. Should you use a hormonal method in this case or chemotherapy using cytostatics?

If we take into account quantitative indicators, then we must choose between hormone therapy (effective in 30% of cases) and combination chemotherapy (the effectiveness of which is twice as high). However, this is a simplified solution to the question, which is really difficult to answer. The reaction of the tumor to hormones is usually more prolonged, and the patient has minimal toxic manifestations.

When chemotherapy develops a more short-term effect, which is accompanied by toxic and psychological complications. Most clinicians in the UK prefer to use hormone therapy as a primary treatment. The choice is facilitated by an ever wider application of the method of analyzing the state of estrogen receptors: hormone therapy should be carried out only among patients with ER-positive tumors.

Recently, the drug fulvestrant (Faslodex), which suppresses estrogen receptor functions, has been proposed. It can be used in patients with hormone-resistant tumors that have developed in postmenopausal women. One of the main advantages of this drug, compared with an estrogen agonist, tamoxifen, is the absence of side effects. It also does not deplete the pool of estrogen in the female body, which occurs when using aromatase inhibitors.

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