Hormone therpay Flashcards
The cancers that are most commonly hormone sensitive are
those arising within tissues under hormonal control of normal cellular proliferation or survival. These include cancers of the
* prostate,
* breast
* and endometrium (sex hormones),
* and lymphocytic malignancies such as lymphoma, leukaemia and myeloma (corticosteroids).
For these cancers, the rate of hormone-dependency is high, and hormone therapy has become a part of standard treatment.
Hormonal treatments have been used at all stages of cancer treatment:
- To shrink primary tumours before (neo-adjuvant) or instead of surgery (primary medical therapy)
- To prevent or delay the growth of micro metastases following surgery (adjuvant therapy)
- To shrink established metastases and improve quality and duration of life (palliative therapy)
usual agent used for hormone therapies and how it works
- Hormonal therapies usually involve steroid hormones.
- As a family, steroids interact with cytoplasmic protein receptors to form functional DNA transcription factors, affecting the transcription of multiple genes.
- Interference with this system may involve removing the hormone, introducing a competing molecule or modulating the receptor.
- Thus a range of therapeutic manoeuvres may be used to alter the hormonal “environment” of the cancer cell.
- In some cases, the presence of cytoplasmic steroid receptors in tumour cells can be used to predict for hormone sensitivity (e.g. oestrogen receptor “ER” in breast cancer). .
most direct form of hormone therapy and its examples
Removing the source of a growth-promoting hormone is the most direct form of hormone therapy. Examples include bilateral oophorectomy in pre¬menopausal women and bilateral orchidectomy in men, to remove the main source of sex hormones. These operations are now largely superseded by medical techniques.
In pre-menopausal women, permanent ovarian ablation may be induced by
radiotherapy
In both men and women, reversible “medical castration” is achieved by… this is unsuitable for postmenopausal women because..
by long-acting LHRH analogues (e.g. goserelin, leuprorelin) which, by receptor down-regulation in the pituitary, block LH and FSH production and, in turn, gonadal hormone output.
These techniques are unsuitable for postmenopausal women, for whom sex hormone production is mainly extra-gonadal, in fat and the adrenal glands.
target for aromatase inhibitors
The rate-limiting step in oestrogen synthesis is the conversion of androstenedione to oestrone by the enzyme aromatase. In postmenopausal women, androstenedione is secreted by the adrenal and aromatized in other tissues including fat and liver. This step is the target for aromatase inhibitors.
The first was aminoglutethimide that is non-specific, also blocking an earlier stage in steroid synthesis, so corticosteroid supplementation is required.
New potent, specific aromatase inhibitors (anastrozole, exemestane, letrozole) are highly effective in clinical trials with greater efficacy and less toxicities.
3 ways you can implement hormone therapy
- Removing the source of a growth-promoting hormone
- hormone inhibitors
- increasing hormones
how does hormone inhibition work and what is the best example?
This approach uses drugs that block the binding of hormones to their receptors in tumour cells. The best known is tamoxifen that acts (in part) as an anti-oestrogen. Tamoxifen is used at all stages of breast cancer treatment.
There are two main types of anti-androgen: how do they work?
There are two main types of anti-androgen.
* Steroidal anti-androgens (e.g. cyproterone acetate) have a dual action. In tumour cells they inhibit the androgen receptor, but in the hypothalamus they substitute for testosterone, so stimulate negative feedback inhibition with subsequent decrease in LHRH release.
* Non¬-steroidal anti-androgens (e.g. bicalutamide) inhibit testosterone in both tumour cells and hypothalamus, so feedback inhibition is lost and serum testosterone levels rise.
* “Maximum androgen blockade” describes the combination of a non-steroidal anti androgen with an LHRH analogue to prevent this effect and is used as a therapeutic strategy in prostate cancer.
examples of increasing hormone levels using natural or synthetic hormones for treatment
Increasing hormone levels using natural or synthetic hormones is sometimes helpful. Glucocorticoids in high concentration induce apoptosis in some malignant lymphoid cells, and form an important component of treatments for lymphoid leukaemias, lymphomas, myeloma and Hodgkin’s Disease.
hormone supplementation is used for which cancers? how does it work?
Hormone supplementation is used in certain sex-hormone sensitive cancers with the aim of inducing negative feedback loops (e.g. oestrogens to down-regulate hypothalamic LHRH in prostate cancer) or tachyphylaxis (down-regulation) of receptors (e.g. high-dose oestrogens in breast cancer).
what are Progestogens and how are they used in treatment?
- Progestogens are synthetic analogues of progesterone (e.g. medroxyprogesterone acetate; megestrol acetate), which may be given orally in high dose for cancers arising in progesterone-sensitive tissues (breast, endometrium).
- They may give direct inhibition of tumour growth via acting as an agonist of the progesterone receptor, but also produce negative feedback on the pituitary/gonadal axis.
- These drugs may also stimulate the appetite and are widely used in palliative medicine for that reason.
