Chemotherapy and Systemic treatment


Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

There are three major types of chemotherapy.

  • Neoadjuvant chemotherapy
    • given before surgery to shrink the size of a tumour
  • Adjuvant chemotherapy
    • given after surgery to reduce the risk of recurrence
  • Palliative chemotherapy
    • Used to control (but not cure) the cancer in settings in which the cancer has spread beyond the breast and localized lymph nodes.
  • Combined therapies
    • combining, for example, non-drug treatments with localized chemotherapy to limit toxocity and achieve better results

Multiple chemotherapeutic agents may be used in combination to treat patients with breast cancer. Determining the appropriate regimen to use depends on many factors; such as, the character of the tumor, lymph node status, and the age and health of the patient. In general, chemotherapy has increasing side effects as the patient’s age passes 65.

Multiple chemotherapeutic agents may be used alone or in combination to treat patients with breast cancer. Chossing the appropriate regimen depends on many factors including: the character of the tumor, lymph node involvement and the age and health of the patient. In general, side effects may be increased as the patient aged.

Commonly used Chemotherapy regimens

The following is a list of commonly used chemotherapy regimens in treatment of breast cancer:

  • FEC: 5-fluorouracil, epirubicin and cyclophosphamide given 3-weekly for 6 cycles
  • AC (or CA): Adriamycin (doxorubicin) and cyclophosphamide given 3-weekly for 4 cycles
  • FAC (or CAF): 5-fluorouracil, doxorubicin, cyclophosphamide given 3-weekly for 6 cycles
  • AC-Taxol: AC given 3-weekly for 4 cycles followed by paclitaxel given either 3-weekly for 4 cycles or weekly (at a smaller dose) for 12 weeks
  • TAC: Taxotere (docetaxel), Adriamycin (doxorubicin), and cyclophosphamide given 3-weekly for 6 cycles
  • CMF: cyclophosphamide, methotrexate, and 5-fluorouracil given 4-weekly for 6 cycles
  • FECD: FEC given 3-weekly for 3 cycles followed by docetaxel given 3-weekly for 3 cycles
  • TC: Taxotere (docetaxel) and cyclophosphamide given 3-weekly for 4 or 6 cycles
  • Dose dense regimen: Some of the regimens above (e.g. AC followed by paclitaxel) may be given in a shorter period (i.e. every 2 weeks instead of every 3 weeks).
  • In addition to chemotherapy, trastuzumab (Herceptin; see Targeted therapy below) may also be added to the regimen depending on the tumor characteristics (i.e. HER2/neu status) and risk of relapse. It is usually given either 3 weekly or weekly for a total duration of 1 year.

Since chemotherapy affects the production of white blood cells, granulocyte colony-stimulating factor (G-CSF) is sometimes administered along with chemotherapy. This has been shown to reduce, though not completely prevent, the rate of infection and low white cell count. Most adjuvant breast cancer chemotherapy regimens do not routinely require growth factor support except for those associated with a high incidence of bone marrow suppression and infection. These may include chemotherapy given in the dose dense fashion i.e. 2-weekly instead of 3-weekly or TAC chemotherapy (see above).

Side effects

Chemotherapy may affect healthy cells. Medicines used with self-help methods can help ease many of these side effects. It is important to tell your doctor if you are having any problems with these or other side effects not listed:

  • Nausea and vomiting, either the day of treatment, or more commonly, several days after. Nausea on the day of treatment is usually well-controlled, but delayed nausea is harder.
  • Loss of appetite.
  • Fatigue is the most common symptom that patients notice and they often do not tell the doctor.
  • Mouth soreness.
  • Hair loss. Whether the hair falls out all at once, gradually, or not at all depends on what drugs are given.
  • Weight gain.
  • Premature menopause. If you are planning to have children, you should discuss this with your doctor before starting chemotherapy, as there may be ways to prevent your periods from stopping or to save ovary tissue.
  • Lowered resistance to infections. Many chemotherapy drugs lower the white blood cell counts in the week or so after treatment. If the blood counts are very low, then an infection can be dangerous.
  • Increased bleeding. Many chemotherapy drugs also lower the platelet counts. Platelets are the body’s first line of defense in blood counting. If the platelet counts are very low, little red spots start to appear on the body, you may bruise or bleed easily, even without any trauma. If this occurs, your doctor needs to be informed.
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Targeted Therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodies and tyrosine kinase inhibitors are two types of targeted therapies used in the treatment of breast cancer. PARP inhibitors are a type of targeted therapy being studied for the treatment of triple-negative breast cancer.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Monoclonal antibodies may be used in combination with chemotherapy as adjuvant therapy.

Trastuzumab (Herceptin) is a monoclonal antibody that blocks the effects of the growth factor protein HER2, which sends growth signals to breast cancer cells. About one-fourth of patients with breast cancer have tumors that may be treated with trastuzumab combined with chemotherapy.

Tyrosine kinase inhibitors are targeted therapy drugs that block signals needed for tumors to grow. Tyrosine kinase inhibitors may be used in combination with other anticancer drugs as adjuvant therapy.

Lapatinib is a tyrosine kinase inhibitor that blocks the effects of the HER2 protein and other proteins inside tumor cells. It may be used with other drugs to treat patients with HER2-positive breast cancer that has progressedfollowing treatment with trastuzumab.

PARP inhibitors are a type of targeted therapy that block DNA repair and may cause cancer cells to die. PARP inhibitor therapy is being studied for the treatment of triple-negative breast cancer.

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Hormonal Therapy

Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormones are substances produced by glands in the body and circulated in the bloodstream. Some hormones can cause certain cancers to grow. If tests show that the cancer cells have places where hormones can attach (receptors), drugs, surgery, or radiation therapy is used to reduce the production of hormones or block them from working. The hormone estrogen, which makes some breast cancers grow, is made mainly by the ovaries.

Treatments which reduce the level of these hormones, or prevent them from working, are commonly used in people with breast cancer. This hormone treatment works best in women with ‘hormone responsive’ breast cancer, i.e. Estrogen Receptor positive and/or Progesterone Receptor positive (ER and/or PR +ve tumours).

Hormone treatments include:

Oestrogen blockers. Tamoxifen has been available for many years and is still widely used. It works by blocking the oestrogen from working on cells. It is usually taken for five years. Other oestrogen blocker drugs are now available such as Fulvestrant (‘Faslodex’)

Aromatase inhibitors. These are drugs which work by blocking the production of oestrogen in body tissues. They are used in women who have gone through the menopause. These drugs include anastrozole (Arimidex), letrozole (Femera) and exemestane (Aromasin).

GnRH (gonadotrophin releasing hormone) analogues. These drugs work by greatly reducing the amount of oestrogen that you make in the ovaries. There are several GnRH analogue preparations; the commonly used one is goserelin (Zoladex). They are usually given by injection and may be used for women who have not yet reached the menopause.

An alternative which may be considered for women before the menopause is to remove the ovaries (or to destroy them with radiotherapy). This stops oestrogen from being made.