Hormone therapy

Question 1

Some cancers are hormone sensitive because…

Answer 1

the tissues they arise from are under hormonal control of normal cellular proliferation or survival

Question 2

Name some cancers that involve hormones

Answer 2

Prostate, breast and endometrium (sex hormones), and lymphocytic malignancies such as lymphoma, leukaemia and myeloma (corticosteriods)

Question 3

What are the uses of hormonal treatments? (across all stages of cancer)

Answer 3

1. To shrink the primary tumours before surgery (neoadjuvant)
2. To prevent or delay growth of micro metastases following surgery (adjuvant)
3. To shrink established metastases and improve quality/ duration of life (palliative)

Question 4

what sort of hormones are most hormonal therapies?

Answer 4

Steroid hormones

Question 5

How do steroid hormones work?

Answer 5

Steriods interact with cytoplasmic protein receptors to form functional DNA transcription factors, affecting the transcription of multiple genes

Question 6

Where are sex hormones produced in post-menopausal women?

Answer 6

Extra-gonadal, in the fat and adrenal glands

Question 7

How is the source of hormones stopped in pre-menopausal women?

Answer 7

Bilateral oophorectomy (outdated)
Long-acting LHRH analogues (e.g. goserelin, leuprorelin), which through receptor down-regulation in the pituitary, block LH and FSH production, and in turn gonadal hormone output

Question 8

What are aromatase inhibitors used for?

Answer 8

To stop oestrogen production in post-menopausal women with hormone-sensitive cancers

Question 9

How to aromatase inhibitors work?

Answer 9

The rate-limiting step in oestrogen synthesis is the conversion of androstenedione to oestrone by the enzyme aromatase.
In post-menopausal women, androstenedione is secreted by the adrenal glands and aromatized in other tissues, including the fat and liver.
This step is the target for aromatase inhibitors.

Question 10

Name some new aromatase inhibitors

Answer 10

Anastrozole, exemstane, letrozole

Highly effective in clinical trials, with greater efficacy and different less symptomatic early toxicities

Question 11

What do hormone inhibitors do?

Answer 11

Block hormones from binding to their receptors in tumour cells

Question 12

How does tamoxifen work?

Answer 12

Acts in part to stop oestrogen binding to it’s receptors -used in all stages of breast cancer treatment

Question 13

Name two classes of anti-androgen used in prostate cancer

Answer 13

1. Steroidal anti-androgens

2. Non-steriodal anti-androgens

Question 14

How to steroidal anti-androgens work?

Answer 14

e.g. cyproterone acetate
They have a dual action.
In tumour cells, they inhibit the androgen receptor, but in the hypothalamus they substitute it for testorsterone, so stimulate negative feedback inhibition with subsequent decrease in LHRH release.

Question 15

How do non-steriodal anti-androgens work?

Answer 15

They inhibit testosterone in both tumour cells and the hypothalamus, so feedback inhibition is lost and serum testosterone levels rise.

Question 16

Give an example of a steroidal anti-androgen

Answer 16

Cyproterone acetate

Question 17

Given an example of a non-steroidal anti-androgen

Answer 17

bicalutamide

Question 18

Describe what a ‘maximum androgen blockage’ entails

Answer 18

The combination of a non-steroidal anti-androgen with an LHRH analogue - used as therapeutic strategy in prostate cancer

Question 19

What is the advantage of a maximum androgen blockade over just a non-steroidal anti-androgen?

Answer 19

Prevents the rise in testosterone levels associated with non-steroidal anti-androgens.

Question 20

Why might increasing hormones sometimes be helpful?

Answer 20

Glucocorticoids in high concentration induce apoptosis in some malignancy lymphoid cells, and form an important component of treatments for lymphoid leukaemias, lymphomas, myeloma and Hodgkin’s disease

Question 21

What hormone induces apoptosis in some malignant lymphoid cells at high doses?

Answer 21

Glucocorticoids

Question 22

Why might hormone supplementation be used in treatment of sex-hormone sensitive cancers?

Answer 22

Aim to induce negative feedback loops e..g. oestrogens to down-regulate hypothalamic LHRH in prostate cancer

Question 23

What are progestogens?

Answer 23

Synthetic analogues of progesterone

Question 24

Give an example of a progestogen

Answer 24

Megestrol acetate

Question 25

When might a progestogen be used?

Answer 25

Can be given orally in high doses 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.

Question 26

Why might progestogen drugs be used in a palliative care setting?

Answer 26

Stimulate appetite