There is an alternative to taking tamoxifen

Practice clinic Cancer Medicine for Women / Breast Center

Anti-hormonal therapy is an essential part of breast cancer treatment. Sometimes people mistakenly speak of hormone therapy. The doctor also speaks of endocrine therapy.

About 70% of all breast cancers have binding sites (receptors) for the female hormones - estrogens and progesterone (also called luteal hormone). If a cancer cell has these receptors, the growth of this cell is promoted by the body's own female hormones (estrogens). The antihormones prevent this effect on the tumor cell.

There are three groups of drugs that differ in their mode of action:

  1. Anti-estrogens (Tamoxifen, Fareston®, Faslodex®)
  2. Aromatase inhibitors (anastrozole, letrozole, exemestane)
  3. GnRH analogues (Zoladex®, Enantone®, Trenantone®)

Therapy standards

Anti-estrogens - block the effects of estrogen

Hormones work according to the key - keyhole principle. To a certain extent, the estrogen represents a key that fits exactly into a keyhole (here an estrogen receptor). Anti-estrogens are substances that fit into the keyhole, but do not have a beneficial effect on the tumor cell. They block the effects of estrogens.

Tamoxifen has been used very successfully for several decades and is still considered a standard therapy today. Fareston® is less well known in Germany - it works in the same way as tamoxifen and has a similar distribution in the Scandinavian countries as tamoxifen in Germany. Faslodex® contains a new substance that is injected every 4 weeks and is currently only used for advanced tumor diseases.

Aromatase Inhibitors - block the formation of estrogen

The aromatase is an endogenous enzyme which supports the formation of estrogens from the precursors (androgens). These precursors are formed, for example, in the adrenal glands and the ovaries. If the enzyme is inhibited, no more estrogen can be formed. This principle also works in the tumor cells themselves.

The various aromatase inhibitors (anastrozole, letrozole, exemestane) can be used in all phases of breast cancer

GnRH analogues - block the production of estrogen in the ovaries

GnRH (gonadotropin-releasing hormone = release hormones) - analogues actually develop their effect in the diencephalon. There they block the usual, regular, rhythmic release of the body's own GnRH. The body's own GnRH in turn causes the release of the control hormones FSH and LH from the pituitary gland. In the absence of these control hormones, the formation of estrogens in the ovary is blocked. This leads to a sharp drop in the body's own estrogen level. The use of GnRH analogues is only useful in selected cases in pre-menopausal women.

All women found to have breast cancer with hormone receptors should receive anti-hormonal therapy.

Adjuvant endocrine therapy:

There is no longer one standard that applies to all patients. Rather, an individualized treatment concept is being developed for each patient today. For the decision on the type of endocrine therapy, tumor biological properties, various prognostic factors and the menopausal status (is the patient before, during or after the menopause) play an important role.

Before and during menopause:

If the patient is before menopause (premenopausal), tamoxifen 20mg / day is the standard. A combination with a GnRH analogue can be useful and necessary in justified individual cases. Aromatase inhibitors are generally not indicated (contraindicated) in these women. A combination of aromatase inhibitors with GnRH analogues has not yet been tested. A study is currently underway in Germany to investigate this treatment (SOFT study). Such treatment can nevertheless be practiced in justified individual cases.

If the patient is to receive chemotherapy, the anti-hormonal therapy is generally only started after the chemotherapy has been completed.

In this situation, the combination of tamoxifen / GnRH analogues is no more effective than the administration of tamoxifen alone. In the current guidelines of the AGO (Fachgesellschaft Arbeitsgemeinschaft Gynäkologische Onkologie) from 2012, the combination of tamoxifen with GnRH analogues is not recommended as a standard! The combination can be considered for women who are younger than 40 years.

In individual cases, the administration of GnRH analogues can be useful in order to prevent rare side effects of tamoxifen administration in women before the menopause (ovarian hyperstimulation syndrome).

After menopause

In women after the menopause (postmenopausal), GnRH analogues are generally not given, as they have no effect.

According to current knowledge, the endocrine standard therapy should be a so-called sequence therapy.

This means that both substance groups (tamoxifen and aromatase inhibitors) should be used as part of this treatment. Both active ingredients are not given at the same time but one after the other.

The AGO treatment recommendations are based on two large, recognized studies (BIG-98 and ABCSG - 8)

Thereafter, women with a high risk of relapse (e.g. affected axillary lymph nodes, G3 tumor or HER2-neu overexpression) should start with an aromatase inhibitor and take it for 2 to 3 years. Thereafter, therapy should be switched to tamoxifen for 3 to 2 years.

The lower risk patients should initially receive tamoxifen for 3 years and then use an aromatase inhibitor for 2 years.

Tamoxifen as a standard therapy for 5 years is now only recommended for women who have shown a very favorable initial situation.

no affected lymph nodes (node ​​negative) and all of the following criteria:

  • Tumor size <2 cm
  • G1
  • no vascular invasion of the tumor
  • Estrogen receptor (ER) and / or progesterone receptor (PR) positive
  • HER 2 / new negative
  • Age ≥ 35 years

Aromatase inhibitors can also be given if there is a tendency to thrombosis (e.g. known coagulation disorders, pronounced varicose veins, high obesity ......) or if complications of the uterine lining occur while taking tamoxifen.

Another study (MA-17) has shown that after 5 years of tamoxifen, the further administration of letrozole can be useful for another 5 years. Women in whom lymph nodes were already affected have benefited in particular.

In none of the studies that compared a 5-year therapy with tamoxifen with a 5-year therapy with an aromatase inhibitor, a significant prolongation of survival through the use of the aromatase inhibitor in comparison with tamoxifen could be demonstrated.

Endocrine therapy of metastatic breast cancer

In the metastatic situation, the endocrine therapy methods are of particular importance because they have a much more favorable side effect profile compared to chemotherapy.

It must be noted that the effect of endocrine therapy begins with a delay. This must also be explained to the patient.

Chemotherapy is preferable to endocrine treatment only in cases of high remission pressure.

All available and approved substances are available for selection.

TamoxifenFulvestrant
Toremifes
AnastrezolGoserelin
LetrozololLeuprorelin
Exemestane
MPA
Megestrol acetate

 

Basically there is a variable therapy cascade. The possible sequence is primarily based on the guidelines of national and international professional societies and the results of phase 2 studies.

If there is a flare-up or progression of the disease during anti-hormonal therapy, another active ingredient can be used.

The side effects of the treatments are different. The most common side effects of all these preparations are menopausal symptoms (hot flashes; sweats; disorders of the mucous membranes in the vagina; recurrent urinary tract infections; general disorders of the skin and hair .....).


Tamoxifen has a higher risk of thrombosis, while 5 years of therapy with an aromatase inhibitor are more likely to detect bone fractures as a result of developing osteoporosis, and more frequent symptoms, especially of the small joints.

Women taking an aromatase inhibitor should pay special attention to bone health. The focus is on regular, consistent physical activity (e.g. Nordic walking, jogging, equipment training, gymnastics or other sporting activities) and a calcium-rich diet (the main calcium donor is milk and everything that is made from it) be taken - ideally in combination with vitamin D. The correct dosage should definitely be discussed with the attending physician.

Tamoxifen has a protective effect on the bones and heart. Changes in the uterus are seen with tamoxifen. In most cases, however, these are not changes in the mucous membrane, as was previously assumed, but rather harmless changes under the mucous membrane in the uterine wall. According to the latest findings, scraping for clarification is only necessary if a noticeable bleeding has occurred.

Less common side effects are muscle discomfort, depression, or visual disturbances.

With anti-hormonal therapy, we have a very good and effective weapon in the fight against breast cancer. If used correctly, the patients benefit noticeably

Status 06/2012