Breast Cancer - Current Treatment

If a patient is found to have an unusual mass or lump, the next step is to determine if it is cancerous. This is done by biopsy. Essentially, a needle is used to extract a small number of cells that are analysed under the microscope. Cancerous cells have a particular physical appearance that trained hospital technicians recognise. If the lump is cancerous it will need to be removed and/or destroyed. A range of treatments can achieve this goal. They include surgery, radiotherapy, chemotherapy, hormone treatment and immunotherapy.

Surgery
In the past, breast cancer patients would often have a whole breast removed (mastectomy). Nowadays, a lumpectomy followed by radiotherapy can often be an option, particularly if diagnosis is early and the tumour is small. Chemotherapy and/or hormone therapy may also be given. A mastectomy is generally only carried out when the tumour is large or involves the nipple.

Hormone therapy
More than two thirds of breast cancers are oestrogen sensitive. That is, the hormone oestrogen stimulates the growth of the breast cancer by binding to specific receptors inside the cell. The drug tamoxifen is an antioestrogen that competes with natural oestrogen for these binding sites in many breast cancer cells. This impairs the normal effect of oestrogen, thus preventing cell proliferation and so slowing down tumour growth.

The use of tamoxifen and other such medicines has dramatically reduced the death rate in women who have oestrogen-sensitive breast cancer.

At menopause the ovaries stop producing oestrogen. But significant levels of this hormone still remain, particularly in breast tumours and fat tissue, because of the presence of the aromatase enzyme, which makes oestrogen from naturally occurring hormones. A form of medication called aromatase inhibitors can be given to post-menopausal women with oestrogen sensitive breast cancers to prevent oestrogen production and to stop the breast cancer growing. Aromatase inhibitors lower oestrogen levels more effectively after the menopause because at this time oestrogen values are much lower, the only source of oestrogen production being through peripheral tissues; the ovaries are no longer a primary source.

Chemotherapy
Chemotherapy is often used to treat breast cancer or to reduce the risk of recurrence after surgery. All chemotherapy drugs cause side-effects and a balance has to be struck between likely benefit and the level of toxicity.

Alkylating agents are among the most widely used in cancer chemotherapy. They act by damaging DNA, thus interfering with cell replication. The taxanes, administered by intravenous infusion, are also potent anti-cancer drugs. They affect cell structures called microtubules, which help cells keep their shape and are used to transport materials inside the cell. In a multiplying cell, the microtubules are rearranged to form a structure called the spindle. The spindle is broken down once cell division is complete. Taxanes prevent cells from breaking down the spindle, and the cancer cells become so clogged with microtubules that they cannot grow and multiply.

Chemotherapy can cause patients to have extreme nausea and vomiting. This can be so bad that the patients decide not to continue their course of treatment. Medicines have been developed to reduce this side effect; this has been done using ferrets, which, unlike most mammals, vomit in a similar way to people.

Radiotherapy
Radiotherapy for breast cancer is usually given using X-rays or cobalt irradiation. Researchers in the UK are currently testing the effectiveness of a new form of radiotherapy called Intensity Modulated Radiotherapy (IMRT) that they hope will be less damaging to the healthy tissue that surrounds the tumours.

Immunotherapy
The use of antibodies is a new approach to treating cancer, including breast cancer. Cancer cells often have cell surface molecules that are found in greater numbers than on normal cells, or are defective. One example is the HER-2 receptor, which is involved in transmitting growth signals from the cell surface to the cell nucleus. About one quarter of breast cancers have higher levels of HER-2 on their surface than normal. These cancers are often resistant to standard treatment and they correlate with poor patient survival. But antibodies to HER-2 are proving to be effective in blocking growth signal transmission and slowing the progression of advanced disease. Herceptin is the first antibody to be approved for the treatment of HER-2 positive breast cancer.

How did we get these treatments?

Chemotherapy agents are often derived from natural products, including the Yew tree [Currie ecology].

In the 1950s, scientists found that hormone changes could lead to breast cancer in rats, but it took many years before this pathway was considered for therapeutic approaches. Tamoxifen was discovered in the 1960s, but it took scientists about 15 years to realize its potential fully as a treatment for breast cancer partly because at the time most research was focused on chemotherapy. However, detailed studies in animals did indicate that it acted like an anti-oestrogen and so it was expected to be useful as both a contraceptive medicine and in the treatment of breast cancer. Although trials as a contraceptive were inconclusive, tamoxifen soon proved active in the treatment of advanced breast cancer. But at the time, there were neither human breast cancer cell lines nor good animal tumour models on which to evaluate tamoxifen. The data to support clinical trials of tamoxifen use alongside surgical intervention and in breast cancer prevention came later – following the availability of a chemically-induced rat mammary tumour model.

Screening thousands of natural compounds to find those that affect cell division led to the development of many current chemotherapy agents. One group, the vinca alkaloids, were derived from the common periwinkle Catharantus roseus e.g. vinorelbine. Others, for example Paclitaxel, were first isolated from the bark of the Pacific Yew tree. Once an effective compound has been discovered, scientists may use the structure of the molecule to design similar, but more potent versions.

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