Antihormonal therapy

Approximately two-thirds of all malignant breast tumors grow dependent on female sex hormones, primarily estrogen. They are formed in large quantities in the ovaries from the first menstruation - the onset of puberty - until menopause - the absence of menstruation. But other tissues also produce estrogens.

After the association of breast cancer with hormone exposure became known, many women had their ovaries removed (ooparectomy) or irradiated. Yet subsequent infertility for young patients was very problematic. Available since the 1970s, antihormonal therapy (also: "endocrine therapy") stops or slows down tumor growth by medication. Often, after treatment, menstruation occurs again; the ability to conceive may be preserved.

Antihormonal therapy, like chemotherapy, also acts throughout the body and destroys even the smallest metastases, which cannot yet be detected by the diagnostic capabilities available today. The advantage over chemotherapy is that there is no direct effect on healthy cells, however, the lack of action of the hormone is also reflected in them. In general, antihormonal therapy is better tolerated and can be continued for many years.

So far, adjuvant antihormonal therapy has lasted mostly 5 years. Recently, however, it has been confirmed that tamoxifen therapy extended by 10 years could further reduce the likelihood of breast cancer recurrence. For postmenopausal women with a high risk of recurrence who have already taken tamoxifen for 5 years, prolonged therapy with an aromatase inhibitor is recommended again for 3 to 5 years. For other endocrine substances and the consistent use of various active substances, there are no studies on a longer therapeutic period, so the recommendation “5 years” remains here.

For metastatic breast cancer, treatment continues until the disease subsides. If necessary, treatment can be continued with another antihormonal agent, or endocrine therapy can be combined with some kind of targeted therapy.

Antiestrogens block receptors on cancer cells
When conducting hormone therapy with the use of antiestrogens, the production of estrogens does not stop, but only the action of estrogens on tumor cells is blocked. Antiestrogens (also SERMs: selective estrogen receptor modulators) occupy the binding sites (receptors) of hormone-dependent tumor cells, to which estrogens normally attach, and thereby cause the growth of these cells. If the receptor is blocked in this way, estrogens can no longer bind and therefore do not reach their effect.

One of the most recent discoveries is the estrogen receptor antagonist fulvestrant. It also occupies the cancer cell's estrogen receptors and turns them off completely, while tamoxifen leaves some residual activity. In addition, fulvestrant leads to the destruction of receptors. Currently, fulvestrant is approved for use, however, only in patients with advanced or metastatic breast cancer.

Tamoxifen is used before and after menopause. After surgery - during adjuvant, additional therapy - reduces the risk for the recurrence of the disease (relapse). With progressive and metastatic tumors, the process of disease development slows down. Currently, fulvestrant is used only in women - mainly after the onset of menopause - in whom breast cancer is already advanced and / or metastasizing and who have previously been treated with tamoxifen. Tamoxifen is taken once a day as a tablet, fulvestrant is given once a month as an injection.

Aromatase antagonists stop estrogen production after menopause

After menopause, when the ovaries have stopped producing estrogen, these hormones are produced in small amounts in other tissues, such as muscle, adipose tissue, and breast tissue. In this case, an enzyme called aromatase plays an important role here. It promotes the conversion of estrogen precursors into estrogen. Aromatase inhibitors are substances that bind to aromatases and thus deactivate them and block the production of estrogen in muscle and fat cells. At the molecular level, there are steroidal and non-steroidal aromatase inhibitors.

Aromatase inhibitors interfere with the production of estrogen in muscle and adipose tissue, but not in the ovaries. Therefore, they are only suitable for women who are already in menopause, ie. after the onset of menopause. They can be used in early and advanced stages of breast cancer. After surgery, they serve as an additional therapy (adjuvant), so they reduce the risk of tumor recurrence. If metastases already exist, aromatase inhibitors can stop tumor growth or slow it down. In the adjuvant setting, aromatase inhibitors are preferred, alternating with tamoxifen. It is individually decided which of the active substances will act first. However, in patients with affected lymph nodes, the sequence is recommended: aromatase inhibitors → tamoxifen. Aromatase inhibitor therapy alone is also possible.

In advanced breast cancer, depending on the adjuvant therapy, various antihormonal therapy options are used in turn. It can also replace a steroidal aromatase inhibitor with a non-steroidal one, or vice versa.

The aromatase inhibitor is taken once a day as a tablet.

GnRH—analogues: hormones that inhibit estrogen production by the ovaries

Gonadotropin analogues—hormone releasing are substances that are similar (analogous) to a hormone produced by the hypothalamus called GnRH (gonadotropin releasing hormone) or also LGRG (LGreleasing hormone). This hormone performs an important task in regulating the menstrual cycle by causing the release of certain hormones (LH and FSH) from the pituitary gland, which in turn contribute to the production of estrogen in the ovaries.

Artificial (synthetic) hypothalamic hormones, GnRH analogs, bind pituitary receptors, which, however, are provided for the body's own hormones, but do not cause estrogen production. As a result, this leads to the cessation of the body's production of its own estrogens. After prolonged stimulation, these pituitary receptors are destroyed, as a result of which the growth of cancer cells is no longer stimulated. GnRH analogues are indicated for patients before menopause. They are prescribed for adjuvant and palliative care, most often in combination with tamoxifen. During chemotherapy, there is no clearly proven effect on the protection of ovarian function, while it cannot be ruled out that they weaken the effect of chemotherapy. And therefore, GnRH therapy is rather undesirable during chemotherapy today. The GnRH analogue is administered as a subcutaneous injection, either as a suspension with a thin needle or as a depot with a thicker needle. There are syringes with a volume of active substance for 1 month (one-month form) and for 3 months (three-month form). The duration of treatment is determined individually.