Russian Breast Cancer.
Health Strategy.

Orthodox methods
of treatment of breast cancer.

Having on hand the results of the research, the attending physician develops a treatment plan. The «gold standard» for cancer treatment is still three approaches: cut, poison and burn cancer cells. That is, surgery and chemotherapy followed by radiation therapy. Hormone-sensitive tumors are also treated with hormone therapy * and immunotherapy. Recently, science and technology have made it possible to solve these problems in a more precise and less traumatic way.

Surgery.

Surgery is a major part of the treatment process for most breast cancers. Whether a patient is a candidate for surgery depends on factors such as the type, size, location, classification, and stage of the tumor, as well as general health factors such as age, fitness, current illnesses, and other medical conditions.

Surgical options.

Depending on the specific case, the following surgical procedures can be performed.

Lumpectomy. Removing the tumor (and the small supply of apparently healthy tissue around it) can help prevent the cancer from spreading.

Lumpectomy Enlarge Image

This gentle operation is possible in the first two stages of cancer development, if the tumor is small (up to 1 cm in diameter), and if it can be easily separated from the surrounding tissue. Lumpectomy allows you to save the main part of the breast due to some change in its volume and shape.

However, it is difficult for the surgeon to choose the site of the cut in order to preserve the maximum of the breast with the maximum of the tumor to be removed. When cancer cells are subsequently found at the edges of the removed piece of tissue, this is called a «positive margin», and if not found, a «negative margin».

With a positive margin, most likely, you will have to do a second removal. And in the most severe cases - to carry out a complete removal of the mammary gland. In any case, the surgery will leave its mark in the form of a scar.

Sentinel node biopsy. If there is no lymph node enlargement, sentinel lymph node biopsy is usually used *.

Sentinel node biopsy Enlarge Image

Certain lymph nodes are the main draining node for the tumor. First, using a contrast agent, find out to which lymph node the tumor lymph drains. This single node can then be surgically removed instead of removing all of the lymph nodes.

A sentinel lymph node biopsy can stop the primary tumor from spreading to other parts of the body through the lymphatic system. In addition, compared to more traumatic surgeries, it is less likely to cause lymphedema *.

If a biopsy of the removed sentinel lymph node does not reveal cancer cells in it, then, most likely, the remaining lymph nodes are also clean. If cancer cells are present, then a decision may be made to remove a few lymph nodes in the armpit to prevent the cancer from spreading further.

Mastectomy. Complete removal of the breast. Although a partial removal of the breast is performed whenever possible, in many cases a radical removal is performed.

Mastectomy Enlarge Image

A simple mastectomy involves removal of the lobules, ducts, fatty tissue, nipple, areola, and part of the skin.

A radical mastectomy also includes the removal of muscles in the chest wall and lymph nodes in the armpit. Removing breasts from both sides of the body is called a double mastectomy.

A mastectomy is not necessarily better than a lumpectomy – breast-conserving surgery combined with chest radiation generally provides better survival outcomes than just unilateral and bilateral mastectomy *.

Removal of axillary lymph nodes. If a biopsy of the removed lymph nodes in the armpit shows the presence of cancer cells in them, then some more of them are removed. In some cases, it may be necessary to remove all axillary lymph nodes.

Modified mastectomy Enlarge Image

Breast reconstruction. Plastic surgery that can reshape the breast so that it looks like a real one. This can be done at the same time as the mastectomy or later. The surgeon may use a breast implant or tissue from another part of the patient's body.

Pros and cons of radical breast cancer treatment.

Advantages. Surgical intervention allows you to quickly, effectively and irreversibly get rid of the visible part of the cancer cells.

Problems. It is difficult to visually determine the boundaries where cancer cells end.

Contraindications. Sometimes doctors are forced to refuse the operation. For example, the tumor has grown so that its removal has become impossible, dangerous, or the patient has serious contraindications for surgical intervention.

Side effects. Surgical procedures are accompanied by the introduction of infection, an inflammatory reaction and a temporary weakening of the immune function. They can cause short-term or long-term pain and further painful sensitivity in the surgical area. Moreover, for unknown reasons, surgery may stimulate metastasis.
Scar tissue forms at the surgical site, the skin around the breast may feel tighter and tighter, and the muscles in the arm may feel tighter or weaker. Surgery involving the lymph nodes often causes swelling, fluid collection, and swelling in the arm. One operation may sometimes not be enough, and then additional operations have to be performed to completely remove the tumor.
Less common complications include deep vein thrombosis, heart or breathing problems, bleeding, reactions to anesthesia. Sometimes there may be a short immobility of the shoulder joint.

Radiation therapy.

Radiation therapy before surgery can help shrink the tumor if the tumor is large and difficult to remove with surgery. And after surgery to remove a tumor, radiation therapy can help destroy any remaining cancer cells and reduce the risk of death and recurrence. When exactly to apply radiation therapy, the attending physician chooses.

X-ray radiation acts directly by destroying cellular proteins, including enzymes and DNA, and indirectly by creating increased levels of free radicals in cells, which lead to cell death. Since cancer cells are more sensitive to such influences, they suffer more from radiation therapy than normal cells.

Problems. Radiation therapy has the same problems with the affected tissue as surgery. There is always the possibility of either not capturing a tumor with radiation, or irreparably damaging nearby healthy tissues with radiation. In recent years, radiation therapy technologies and equipment have been greatly developed, which makes it possible to irradiate a given target more accurately and sparingly.

Radiation therapy is used about a month after surgery or chemotherapy, and also in combination with chemotherapy, depending on the treatment regimen drawn up by the doctor. Irradiation of the tumor zone can be performed both from the outside and from the inside, using various devices and technological innovations. Each radiation session lasts a few minutes, and the patient may need three to five sessions per week for 3-6 weeks, depending on the individual case.

Side effects of radiation therapy may include redness, darkening, dryness, or irritation of the skin in the treated area. Fatigue is another common side effect, especially during the later weeks of treatment and for some time afterwards. A serious side effect of radiation therapy is a decrease in the immune function of the body. There are also a number of long-term effects, such as lymphedema (soft tissue swelling), weakening and fracture of the costal bone, heart problems, post-radiation pneumonia, and peripheral neuropathy of the shoulder and arms. Finally, a meta-analysis of clinical trials found that although radiation therapy for early breast cancer reduced breast cancer mortality by an average of 13.2%, it increased mortality from other causes by 21.2% *.

Chemotherapy.

Breast chemotherapy is used to kill cancer cells with chemical toxins. The most commonly used chemotherapy drugs disrupt the cycle of cell division. And since cancer cells are rapidly dividing cells, this effect is more detrimental for them than for normal cells.

Neoadjuvant chemotherapy (or primary general chemotherapy) may be used before surgery to reduce the size of large tumors. This type of chemotherapy often makes breast-conserving surgery possible and helps to pre-evaluate the effectiveness of the chosen therapeutic agent.

Adjuvant chemotherapy may be used after surgery or radiation therapy to kill any remaining cancer cells that may not have been removed during these procedures.

Chemotherapy can also treat cancers that have metastasized, as well as reduce some of the symptoms, especially in the later stages of the disease. Chemotherapy is not always justified, and the need for it and the choice of therapeutic agents is decided by the attending physician, taking into account many conditions, such as the size of the tumor, its subtype and aggressiveness.

Chemotherapy is carried out in several cycles, alternating periods of treatment with subsequent periods of recovery. Usually several chemotherapy drugs are combined in order to achieve wider target coverage and reduce the development of tumor drug resistance *.

Examples of chemotherapy drugs used to treat breast cancer include: anastrozole (Arimidex®), capecitabine (Xeloda®), carboplatin, cisplatin (Platinol), cyclophosphamide (Cytoxan®), docetaxel, paclitaxel (Taxol®), doxorubicin (Adriamycin), epirubicin, doxorubicin liposomal injection (Doxil®), exemestane (Aromasin®), vinorelbine, fluorouracil (5-FU), gemcitabine (Gemzar®), ixabepilone (Ixempra®), letrozole (Femara®), bevacizumab (Avastin®) , pertuzumab (Perjeta®), and trastuzumab (Herceptin®).

Depending on the color of the chemotherapy drug used, chemotherapy is conventionally divided into red, blue, yellow and white.
«Red» chemotherapy uses doxorubicin, idarubicin, or epirubicin.
«Blue» chemotherapy uses mitoxantrone or mitomycin.
«Yellow» chemotherapy uses fluorouracil, methotrexate, or cyclophosphamide.
«White» chemotherapy uses taxol.

Chemotherapy drugs can be delivered in several ways: by mouth (by mouth as a tablet or liquid); intravenously (by infusion into a vein); externally (in the form of a cream on the skin); injection; directly (through a lumbar puncture or subcutaneous device).
When chemotherapy drugs travel through the bloodstream to reach cells throughout the body, this is called systemic (general) chemotherapy. When chemotherapy drugs are directed to a specific area of the body, this is called topical chemotherapy.

Side effects. Although chemotherapy targets cancer cells, systemic chemotherapy circulates throughout the body and therefore also damages healthy, rapidly dividing cells and causes many negative side effects. Most often it is nausea; vomit; fatigue; loss of appetite; pain in the mouth; hair loss; ulcers of mucous surfaces; a decrease in the number of blood cells and increased susceptibility to infections. Additional medications can help relieve many of these side effects.

Other common side effects include: allergic reactions; temporary problems with vision and hearing; lowering blood pressure and heart rate; dehydration; muscle or joint pain. Many chemotherapy drugs can affect the future ability to have or bear children.

Targeted therapy.

Targeted therapy is a selective therapy in addition to chemotherapy drugs, and marks the transition from universal therapies to more specific, individualized therapies. Individual therapies reveal abnormalities that can be found in each tumor DNA profile. While standard chemotherapy affects every cell in the body, targeted therapies target drugs or other specially designed substances (such as immune system proteins developed in a lab) to fight cancer cells.

The goal of targeted therapy is to interfere with genes or proteins involved in tumor growth in order to block the spread of the disease. Because targeted therapy selectively targets cancer cells, it can result in less side effects than standard chemotherapy.

Monoclonal antibodies use specific antibodies (protein molecules produced by B cells as an innate immune defense) that are directed against antigens (substances that can induce a specific immune response) located on the surface of tumor cells. An example would be trastuzumab (Herceptin®) for the treatment of breast tumors with excess HER2 protein.

Side effects. Targeted therapy is generally safer than chemotherapy because non-cancerous cells are only slightly affected. Side effects caused by it may include mild allergic reactions such as hives.

There are other types of targeted breast therapies. For example, targeting cancer cells not with chemotherapy drugs, but with immune cells. However, all of them have not yet gone beyond the limits of experiments.

Hormone therapy.

Hormone therapy is usually used after surgery, but sometimes it can be used to reduce tumor growth without surgery. For some patients who cannot undergo surgery, chemotherapy, or radiation therapy, hormone therapy may be the only treatment option.

Hormone therapy used after other therapies is intended to prevent the recurrence of hormone-sensitive breast cancers. These are well-known tumors such as those susceptible to estrogen receptors (ER-positive) and progesterone receptors (PR-positive), as well as HER2-positive tumors.

Hormones are chemicals produced by some cells to send control signals to other cells, sometimes very far away. By suppressing the signaling of some hormones or increasing the signaling of others, it is possible to stimulate or suppress the growth of cells sensitive to these hormones.

In breast cancer, hormonal therapy is aimed at reducing the growth-stimulating (proliferative) effect of estrogen, and uses several methods - reducing the absolute level of estrogen, reducing the activity of hormones binding to their receptors, and reducing the ratio of less aggressive hormones and their metabolites to less aggressive ones.

Examples of hormone therapy include: hormone supplements, estrogen receptor inhibitors, aromatase inhibitors, spaying, or suppression of estrogen production. The duration of taking the drugs usually lasts no more than 5 years.

Hormonal supplements eliminate the deficiency of certain hormones and also help correct hormonal imbalances. More common than other imbalances is the so-called "estrogen dominance" - the predominance of estrogen (which promotes proliferation) over androgen (which counteracts proliferation). The use of bioidentical hormones usually does not cause negative side effects, unlike synthetic hormones.

Selective estrogen receptor modulators (SERMs) bind to estrogen receptors on breast cancer cells, isolating estrogen from interacting with cancer cells. They do not reduce the concentration of estrogen, but they deprive it of the ability to influence hormone-sensitive cells, which as a result prevents their growth.

Tamoxifen is the most widely used hormone therapy used to prevent the recurrence of breast cancer. This drug may also be used for some women who are at high risk of developing breast cancer.

These therapies are limited because none of the SERMs show any effect on ER-negative breast cancer subtypes *.

Side effects. Patients may experience flushing during therapy; dryness and irritation of the vagina; decreased sex drive and mood changes.

Aromatase inhibitors block the formation of estrogen by binding to an enzyme (aromatase) responsible for the production of estrogen. When estrogen production stops, cancer cells lose their incentive to grow and divide.

Side effects. Aromatase inhibitors do not have gynecological and thromboembolic side effects, unlike tamoxifen and other SERMs. They are, however, associated with a decrease in bone mineral density leading to an increased risk of fracture, as well as a possible increase in cardiovascular problems. Aromatase inhibitors also cause joint and muscle pain and an increased risk of weak and thinning bones (osteoporosis).

Several factors influence the type of hormone therapy, including the age of the patient, the type and size of the tumor, and the presence of hormone receptors on tumor cells.

Other clinical treatments for breast cancer.

Modern clinics also practice or study other treatments, mainly as an adjunct to the main therapy.

Hyperbaric oxygen therapy is a procedure for additional oxygenation of the blood and tissues of the body directly, without the help of red blood cells. This therapy allows you to increase the effectiveness of other treatments, such as radiation or chemotherapy, which use oxidative stress to damage cancer cells.

Hyperthermia is a therapy that uses a controlled, temporary increase in the temperature of the whole body or a target area of the body to help make cancer cells more vulnerable to the effects of other treatments, such as radiation therapy and certain chemotherapy drugs.

Photodynamic therapy is a therapy that uses a stream of photons of a given power and wavelength to irradiate a photosensitive substance, which, after a preliminary injection, selectively accumulates in cancer cells. As a result of light exposure, cancer cells die from overheating, oxidative stress and lack of nutrition *. Unlike standard therapy, photodynamic therapy does not suppress immune function, but rather enhances the immune damage of cancer cells *.
The effectiveness of photodynamic therapy can be high, but it is determined by the depth of penetration of photons into the tissue, which is limited to only a few millimeters.

Immunotherapy is a broad category of therapy that uses the body's immune system to fight cancer cells. Immunotherapy drugs are designed to alert the immune system to these mutated cells so they can find and destroy them.

Immunotherapy falls into three main categories:
- checkpoint inhibitors, which disrupt the molecular signals that allow cancer cells to hide from immune attack;
- cytokines - protein molecules that help regulate and control the immune system;
- cancer vaccines, which are used to treat and prevent cancer by targeting the immune system *.

Side effects. Immunotherapy can cause a variety of side effects, including fatigue, nausea, mouth ulcers, diarrhea, high blood pressure, and fluid buildup, usually in the legs. Patients with breast cancer, in particular, may experience fever, chills, pain, weakness, vomiting, headaches, and rashes. The side effects of immunotherapy usually become less severe after the first course of treatment.

Ultrasound therapy uses the energy of ultrasound to destroy the tumor, and in some cases can be considered as an alternative to surgery. Although it can be considered as a non-invasive therapy, it is only applicable to very small tumors.

Cryogenic therapy is a procedure for short-term freezing of target tissues using extremely low temperatures. Usually it is used for metastases with a diameter of not more than 3 centimeters. During the freezing process, ice crystals are formed that destroy the frozen cells, which die after thawing. Significantly fewer positive biopsy results have been reported after cryoablation than after radiotherapy * *.

Anti-angiogenic therapy inhibits the creation and growth of blood vessels in the tumor, which allow it to receive nutrition.

Viral therapy uses viruses to kill tumor cells. Oncolytic viruses can infect and replicate in cancer cells, eventually causing their death and releasing more viruses to infect other cancer cells. Such specific viruses are selective because they cannot replicate in normal cells. This promising therapy is still under development *.

Conclusions.

As you can see, traditional therapy aims to destroy cancer cells and tumors in general, for which it uses various approaches. This does not guarantee either the full achievement of the goal, or the impossibility of relapse. Moreover, such treatment contributes to the selection of the most resistant to therapy clones of cancer cells, which in the future can form an even more dangerous and malignant tumor.

In fact, the task of treatment is not only to destroy the neoplasm artificially or naturally, but also to create conditions under which the risk of cancer recurrence will be minimal, and the chance of its destruction will be maximum.

To do this, you can use the following therapeutic areas:
- containment of tumor cell division using various approaches: reduction of growth and proliferative signals, energy deficit, stimulation of apoptosis, etc.;
- containment of tumor growth with the help of anti-invasive agents;
- restoration of the natural metabolism of cells (return to the production of cellular energy through oxidative phosphorylation in mitochondria instead of its production through fermentation in the cytosol of the cell) with the help of an adequate supply of resources and a favorable microenvironment;
- restoration of cell functionality (differentiation).

 

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