Drug treatment
Antioestrogens
Aromatase inhibitors
Bisphosphonates
Corticosteroids
Cytotoxic Agents
Gn RH (LHRH) Agonists
Progestogens
Sex hormones and antagonists
Antioestrogens
The anti-oestrogens or oestrogen receptor antagonists include tamoxifen and toremifene.
Tamoxifen is widely used as an adjuvant endocrine treatment in both pre and post-menopausal breast cancer. It is also used as a first line endocrine treatment in patients with advanced disease.
Side-effects are less common with tamoxifen than with androgens or oestrogens but patients with bony metastases may experience exacerbation of pain, sometimes associated with hypercalcaemia.
The partial agonism of tamoxifen and toremifene may stimulate the uterus and give rise to endometrial changes including hyperplasia, polyps and cancer. This risk must, however, be viewed in the context of enhanced survival associated with tamoxifen treatment in early breast cancer.
Toremifene is at present only indicated for the treatment of metastatic breast cancer.
Aromatase inhibitors
There are two groups of aromatase inhibitors, selective and non -selective.
The non- selective inhibitor aminoglutethimide lowers oestrogen levels by inhibiting aromatase action.
They also have effects on adrenal steroidogenesis. Treatment is limited to the management of advanced disease in post-menopausal women.
The side-effects of treatment include lethargy, rash, nausea, dizziness and the symptoms of adrenal insufficiency.
Selective inhibitors include anastrozole, exemestane and letrozole. These agents also lower oestrogen levels by inhibiting aromatase action and have the same indication as the non-selective inhibitors but, because they do not impair adrenal steroidogenesis, no replacement therapy is required.
Side-effects are also less pronounced and include: the effects of oestrogen withdrawal; nausea; vomiting; asthenia.
Bisphosphonates
Bisphosphonates (specifically disodium pamidronate and sodium clodronate) may be used first line in the treatment of hypercalcaemia of malignancy.
They may also be useful in the management of osteolytic lesions and associated bone pain in metastatic spread of breast cancer.
Bisphosphonates are usually initiated by hospital physicians following investigation of the patient.
Some patients benefit from long term oral administration.
Steroids are contraindicated in the treatment of hypercalcaemia.
Corticosteroids
Corticosteroids have a use during the course of breast cancer.
During the treatment of primary disease, steroids (often dexamethasone ) are used in conjunction with other antiemetics to alleviate the side-effects of potent cytotoxic agents, particularly in delayed emesis.
Following radiotherapy, local steroid creams can help relieve skin itching.
If the disease has metastasised to the brain, dexamethasone is very useful in reducing oedema around the metasases and reducing intracranial pressure.
Oral steroids are frequently used to stimulate the appetite, in the short term.
One of the main side effects of corticosteroids is gastro-intestinal irritation. This may often be prevented by the use of H2-receptor antagonists.
Cytotoxic Agents
Various cytotoxic agents are used as adjuvant treatment in primary breast cancer, usually following surgery, and in the management of metastatic disease.
Combinations of drugs improve survival and control symptoms better than single agents (although more recently developed drugs e.g. taxoids are usually given as single agents).
The agents used, and course of treatment, depends on the indications, local practice and prognostic factors.
All cytotoxic agents cause side-effects and it is important to establish the advantages of therapy prior to treatment. The treatment should be given by experienced personnel in designated departments.
Cytotoxic drugs fall into different classes, each with characteristic anti-tumour activity, sites of action and toxicity. Most agents have generally similar side-effects but some agents have specific problems:-
Emesis or vomiting is a common feature which can be mild, moderate or severe depending on agents used. Oral antiemetics can be used pre-medication in mild or moderate vomiting.
They can also be used post-medication. Suppositories can also be useful. In moderate emesis oral steroids pre-medication and additional treatment with a specific 5HT3 serotonin antagonist may be necessary. Delayed emesis has been greatly improved by the use of dexamethasone for 3-5 days post treatment.
In the case of severe emesis, specific serotonin antagonists are most effective in controlling early emesis. Intravenous administration of a single dose, usually with dexamethasone, is widely used.
Bone marrow suppression is a common problem with some cytotoxic agents. It usually occurs 7 to 10 days after treatment. Full blood counts are used prior to treatment in order to monitor doses.
Treatment may be delayed if marrow recovery has not occurred. Any case of infection during or shortly after cytotoxic treatment must be regarded as a medical emergency and the patient should be referred back to the oncologist *or breast unit.
Alopecia is a common complication of cytotoxic therapy but is usually reversible.
Teratogenic effects are common with cytotoxic agents. Chemotherapy is thus contraindicated in the first trimester of pregnancy but has been used in the second and third trimesters.
Contraceptive advice must be given prior to starting therapy.
Local tissue necrosis can occur with some intravenous preparations if extravenous leakage occurs.
Specific side-effects are related to individual agents. It is advisable to refer to the drug data sheet / Summary of Product Characteristics for further information.
*It is increasingly common and good practice for patients who are receiving chemotherapy to carry a card detailing the treatment given, emergency procedures and contact numbers.
Gn RH (LHRH) Agonists
GnRH (LHRH) or gonadotrophin-releasing hormone agonists may be used for the treatment of advanced breast cancer in pre- and peri- menopausal women.
They produce the symptoms of the menopause by down-regulating gonadotrophin release which leads to suppression of ovarian function and hence a marked decrease in oestrogen production and release.
The only GnRH agonist currently licensed for this indication is goserelin (to be given as a monthly depot).
With goserelin the pharmacological effects noted in women include hot flushes and sweating, side effects include the following have also been noted: mood changes including depression, vaginal dryness; arthralgia ; skin rashes; rare incidences of hypersensitivity .
Rarely breast cancer patients with metastases have developed hypercalcaemia on initiation of therapy.
Progestogens
Progestogens are used for second or third line treatment of advanced breast cancer.
Agents usually used are medroxyprogesterone acetate or megestrol acetate.
Adrenocorticoid effects at high dose may give rise to symptoms which include fluid retention and oedema, sodium retention, hypertension and weight gain.
Sex hormones and antagonists
Sex hormones and hormone antagonists play an important role in the treatment of metastatic breast cancer and in some cases as an adjuvant treatment in early disease. Included in this group of drugs are:-
- Antioestrogens
- Aromatase inhibitors
- GnRH (LHRH) agonists
- Progestogens
Refer to the individual rationales for further detailed information.
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