Chemotherapy for breast cancer metastasis

Chemotherapy is firmly established as one of the main treatments for breast cancer. Although chemotherapy has gained popularity later than other therapeutic measures, it has proven to be an effective tool for both primary treatment (adjuvant therapy) and a common tumor process, which is accompanied by the formation of metastases.

In breast cancer, compounds from many chemical classes exhibit antitumor activity: alkylating compounds, antimetabolites, cell spindle poisons, antibiotics, taxanes, and others. The ability to objectively monitor the state of the tumor, along with the often observed improvement in the well-being of patients, allows the use of these drugs in detecting metastases.

With metastasis to the skin, lymph nodes and soft tissues, treatment is more effective than with metastases in the liver and lungs. The smallest therapeutic effect was observed in bone metastases. The antitumor activity of chemicals does not depend on the sensitivity of the tumor to hormonal therapy. In the past few years, the antitumor activity of taxane derivatives such as paclitaxel and docetaxel has been detected.

These drugs can be used to treat patients with recurrent and metastatic tumors when other drugs are ineffective. The experience of successful use of combination chemotherapy in Hodgkin’s disease and acute leukemia allowed the use of combinations of various chemotherapy drugs for the treatment of breast cancer. Initially, a five-component formulation was used consisting of vincristine, methotrex-a, cyclophosphamide, prednisolone, and 5-fluorouracil (5-FU).

It was assumed that in this case it would be possible to obtain the maximum antitumor effect. It turned out, however, that the effectiveness of the formulation does not exceed 50%. Subsequently, many other formulations have been proposed and tested. It is difficult to say which of them is the most effective. Many formulations include doxorubicin, which, even when isolated, has a strong antitumor effect, and, as such, is used in the treatment of patients with recurrent breast cancer, as well as an adjuvant therapy agent.

At present, instead of using the same drugs in low doses, they prefer to alternate recipes of different composition. It can be assumed what manifestations of toxicity will develop in the patient upon the appointment of a particular formulation. Basically the toxic complications inherent in each component are summed up, and usually there are no new ones. For CMF, for example, nausea, stomatitis and cystitis are characteristic, and for VAP (vincristine, doxorubicin and prednisone), the characteristic manifestations of toxicity are the development of neuropathy and alopecia.

Patients with doxorubicin-resistant tumors are treated with drugs of the taxane group, and now they are successfully used in the mode of adjuvant therapy. Despite the high antitumor activity of chemotherapeutic agents and their widespread use in the treatment of patients with metastatic breast cancer, the life expectancy of patients increases slightly or does not change at all.

An increase in antitumor efficacy and survival of patients can be achieved with more intensive formulations. It was suggested that the use of high doses of drugs in conjunction with the introduction of supporting stem cells is advisable, but this has not been confirmed in recent studies.

Of course, in patients for whom treatment is effective, the prognosis is better than in cases where chemotherapy does not help much. With the ineffectiveness of chemotherapy should compare the maximum benefit that the patient can receive from treatment, with the adverse effects of side effects from the use of chemotherapy.

This may be one of the reasons for the ineffectiveness of combination chemotherapy in patients with a metastatic form of breast cancer according to the criterion of overall survival. Another reason is that the cytotoxic effect is often short-lived (sometimes several months) and, obviously, is more pronounced in patients with a more favorable prognosis than in patients for whom chemotherapy is ineffective.

One of the most important moments in cancer chemotherapy is to form a group of patients for whom chemotherapy may be effective, and not re-treat those for whom the therapeutic effect is unlikely. So, it is more likely that chemotherapy will be effective in patients with metastases in soft tissues rather than bones, in cases with a limited number of metastases, as well as in those patients who have not previously received cytotoxic drugs. The sensitivity of a tumor to chemotherapy is little dependent on the state of the estrogen receptors.

Recently published results of a study in which the effectiveness of the drug Trastuzumab (Herceptin), which is a monoclonal human antibody, was studied. Patients with tumors expressing a gene that encodes epidermal growth factor receptor synthesis (HER-2) were selected. For such tumors of the mammary gland is characterized by extremely unfavorable prognosis. As a result of treating patients, overall survival improved: the interval free from signs of disease increased from 4.6 to 7.4 months.

However, there was a cardiotoxic effect. Although the increase in survival in the treated group of patients is small, the study represents a real step towards biological treatment of tumors using specific targeted drugs. The effectiveness of the formulation, which includes Trastuzumab, was also confirmed by other studies.

Currently, this drug is widely used in several clinics as a means of adjuvant therapy mainly for the treatment of patients with a common tumor process, and in cases of tumors insensitive to the action of hormones. Finally, it is necessary to mention drugs such as pamidronate and bisphosphonates. They are effective in treating patients with bone metastases. Many studies have found that monthly infusions of pamidronate (at a dose of 90 mg), together with hormonal or chemotherapy, reduce the degree of metastasis and alleviate pain.

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