Chemotherapy & Biological Therapy

What Does Chemotherapy Treatment Involve?

The specific drugs used will vary from one hospital to another, and also according to the type of breast cancer present. The chemotherapy usually consists of several drugs given in combination, with rest intervals to allow the recovery of normal cells. The drugs can be given by mouth or by injection. The second method may require the insertion of a catheter into a large vein, e.g. Port-a-cath. The treatment is performed on an outpatient basis.

Chemotherapy Regimens

Three commonly used regimens are outlined below. They are named according to the drugs used.

CMF (First Generation)

This mild regimen consists of cyclophosphamide, methotrexate and fluorouracil. Six courses of the combination are given over a period of six months. This protocol is less effective (by approximately 4%) and less likely to cause hair loss than the other two regimens.

FEC (Second Generation)

This combination consists of fluorouracil, epirubicin (anthracycline) and cyclophosphamide. Is given over six months. Chemotherapy regimens containing epirubicin are more effective than CMF, particularly in more aggressive tumours. However, the side-effects of epirubicin are more severe.

Taxane-containing regimens. (Third Generation)

Taxanes (T) also known as spindle poisons are usually used in combination with anthracycline (A) sequentially or concurrently. The commonest protocol consists of 4 cycles of AC (anthracycline + cyclophosphamide) followed by 12 cycles of weekly Taxol.

Carboplatin

Carboplatin is particularly effective against breast cancer assosciated with BRCA1 gene mutation. It can be used alne or in combination with other drugs (given by injection).

Capecitabine (Xeloda)

This chemotherapy drug is relatively less toxic than others andis taken in the form of a tablet (twice daily). It is usually used to treat recurrent discharge. Recent evidence shows that it is effective against triple negative breast cancer that has not responded well to standard chemotherapy.

What are the Side-effects?

As mentioned earlier, chemotherapy affects cells that are growing/dividing quickly, such as cancer cells. However, it also affects some normal cells, such as blood and bone marrow cells. This causes a variety of side-effects, according to the type of blood cell involved
(Table below).

Type of blood cell affected
Red blood cell (RBC) White cell (WBC) Platelets
Symptom Anaemia Risk of infection Easy bruising
Reason RBCs carry oxygen to the body’s tissues WBCs fight infection from bacteria, viruses, etc Platelets help to stop bleeding
Effects Tiredness, shortness of breath, pale skin Fever, feeling unwell, sore throat, low blood pressure Bruising/internal bleeding after minor injuries
Treatment Blood transfusion Antibiotics, WBC growth stimulants (G-CSF) Avoid injury and certain drugs (such as aspirin), platelet transfusion

Side-effects affecting other cell types include the following:

  • Nausea and vomiting – is the commonest side-effect of chemotherapy. Several drugs are used to prevent this problem, such as Stemetil, Zofran, Maxalon and steroids.
  • Hair loss – this only occurs with certain drugs. They damage cells in the hair root, resulting in the hair dying and falling out. A wig can be worn until the hair cells recover and the hair re-grows. Hair usually recovers to normal levels within a few months of completing chemotherapy. Cooling the scalp with an ice pack during treatment can reduce this side-effect. This is less likely to occur with weekly Taxol alone or CMF protocols.
  • Psychological effects – feelings of depression and anxiety are common, and are usually only temporary. Counselling and social support are of great benefit, but some people may require antidepressants.
  • Diarrhoea or constipation may occur in some patients.
  • Irregular or absent periods – can be unpredictable and may be reversible after chemotherapy finishes. Some experts believe that the cessation of periods indicates a good response to chemotherapy.
  • Reduced fertility – chemotherapy can damage the ovaries, thus reducing fertility.
  • Other side-effects – these include skin sensitivity, discolouration of urine, vaginal dryness, heart problems, inflammation of the lining of the mouth and gut, heart damage, cystitis and bowel damage.

Biological Therapy

Certain new drugs can target proteins on the surface of cancer cells and block their growth. Herceptin is such a drug and can be used in some cases of invasive breast cancer that contains special proteins known as Her-2 receptors. This drug is better tolerated than chemotherapy. Her-2 positive breast cancer tends to behave more aggressively than Her-2 negative breast cancer. Herceptin can be used alone or in combination with chemotherapy in women with advanced (metastatic) breast cancer that contains Her-2 proteins. The author also recommends the use of this drug in women undergoing chemotherapy for early invasive breast cancer which is positive for Her-2. In these cases. Herceptin is given three weekly for 1 to 2 years. The drug is not recommended in patients with significant heart problems.

Immunotherapy

Invasive breast cancer that expresses the growth receptor Her2 (20% of cases) can be treated with certain antibodies targeting the Her2 protein such as Herceptin and Pertuzumab. These drugs are uaually used with chemotherapy prior to surgery.

Advanced triple negative breast cancer can be treated nowadays with an antibodies directed against PD-1 and PDL-1 proteins  on the surface of tumour or immune cells infiltrating the tumour.

Pembrolizumab is a humanized monoclonal antibody that binds to PD-1 and blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.  This example of immunotherapy has been recently approved for advanced breast cancer

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