RECONSTRUCTIVE BREAST SURGERY
STRATEGIES AND BASIS FOR THE USE OF CHEMOTHERAPY
What is the fundamental objective of the first treatment?
The objective of the first treatment should be in proportion to the spread of the disease, to remove all the abnormalities present, but with the minimum interference possible.
What is breast conservation therapy?
Almost all women with breast cancer undergo surgery. In lumpectomy only the tumor and a narrow margin of surrounding normal breast tissue is removed. Afterwards radiation therapy is given for approximately 6 weeks. This combination (lumpectomy and radiation therapy) is know as breast conservation therapy. This is an option for many women with breast cancer, but not for all of them.
When is breast conservation therapy not indicated?
Breast conservation therapy will probably not be recommended in the following situations:
1. Women with two or more tumors in the same breast, too far apart to be removed together.
2. Women who have had surgery but not all the cancerous area was removed.
3. Pregnant women, in order to avoid radiation therapy during pregnancy.
What about mastectomy?
In a simple or total mastectomy the surgeon removes the entire breast, but does not remove underarm lymph nodes or muscle tissue from beneath the breast. Modified radical mastectomy involves removing the entire breast and some of the axillary (underarm) lymph nodes. This is the most common procedure for woman with breast cancer who have their entire breast removed.
Why are axillary lymph nodes removed?
If a woman has a radical mastectomy or a modified radical mastectomy, her doctors need to know if cancer has spread to the lymph nodes, where the cancer cells can enter into the blood stream and be carried throughout the body.
Before doctors thought that the more lymph nodes that were removed, the lower the risk of distant spread metastasis and the higher the possibilities of recovery. Nowadays we know that systemic therapy (chemotherapy and/or hormone therapy) offers the best chance of destroying cancer cells that have spread outside the breast.
Ideally, the surgeon wants to find the “sentinel node”—the first lymph node into which a tumor drains, and the one most likely to contain cancer cells. This is a new technique that only a highly skilled team can carry out.
How is the sentinel node identified?
In the biopsy of a sentinel node the surgeon injects a radioactive substance or a blue dye into the area around the tumor. Lymphatic vessels carry these substances into the sentinel node. The doctor can either see the blue dye or detect the radioactivity with a Geiger counter. He or she then removes the lymph node for analysis. If the sentinel node contains cancer, the surgeon will perform an axillary dissection — removal of more lymph nodes in the armpit.
If the sentinel node is cancer-free, the patient will not need more lymph node surgery and can avoid the side effects of full lymph node surgery, which are described below.
Why is the sentinel lymph node so important?
Various studies have demonstrated that if the sentinel lymph node is not affected it is almost impossible for the axillary lymph nodes to be, and thus they do no need to be removed for clinical analysis.
On the other hand, if the sentinel lymph node is affected, it is necessary to remove axillary lymph nodes for analysis.
I still don’t understand the need to analyze the axillary lymph nodes if the sentinel lymph node is affected. Because in this case we have to suppose that the axillary lymph nodes are too.
Could you please explain this?
If the sentinel lymph node is affected and the axillary lymph nodes are not removed, we lose crucial information: the number of lymph nodes involved.
Regarding the prognosis and the treatment strategy (the way surgery, radiation therapy, chemotherapy and hormone therapy are combined) having 0 lymph nodes affected is not the same as having from 1 to 3, or 4 to 10, or more than 10 affected. Thus, it is absolutely necessary to establish the number of lymph nodes involved when the axillary nodes are thought to be affected.
Please explain the possible secondary effects of removing the axillary lymph nodes.
When a patient undergoes axillary lymphatic surgery, she can experience a loss of sensitivity, temporary or permanent, in the skin on the upper inner part of the arm; and surgery can also limit mobility of the arm and the back. Since the lymphatic vessels don’t drain normally, fluids can accumulate and cause swelling in the hand and arm, a condition called lymphedema. No one can predict which patients will develop this condition, nor when it will occur.
Lymphedema can occur right after surgery, months, or even years later.
Patients can take precautions to try to prevent lymphedema, or at least to keep it under control. Talk with your doctor to get more details.
What measures can I take to try to prevent lymphedema?
Among the precautions you can take to try to prevent lymphedema are:
-Avoiding having blood taken from the same side of the body as the axillary surgery.
-Don’t allow your blood pressure to be taken using that arm. If you need to be hospitalized for any reason, tell the health care staff about your problem.
-Be on the watch for tightness or swelling in the arm or hand. If this should occur, tell your doctor immediately.
-If necessary, use a well-designed compression sleeve.
Wear gloves whenever you are in the garden or engaged in any activity where you run the risk of being cut.
What role does radiation therapy have in the treatment of breast cancer?
Firstly, radiation therapy can be used to reduce the size of the tumor before surgery. In this case, it would facilitate breast conservation therapy by reducing large tumors to a size that would allow them to be removed by lumpectomy. However, presurgical chemotherapy, known as neoadjuvant chemotherapy, is nowadays preferred in these circumstances.
Another use of radiation therapy is to destroy any cancer cells remaining in the breast, the chest wall, or the armpit after surgery. This is usually done when the tumors removed are large, more than 4 or 5 centimeters in diameter, or when there are more than 3 lymph nodes involved. In these cases, the risk of residual cells is greater.
Another extremely important use of radiation therapy is in breast conservation therapy. When only the tumor is removed (lumpectomy) or part of the breast (segmental mastectomy), or up to one-quarter of the breast (quadrantectomy), logically a much larger part of the breast is left untreated. Statistical studies have demonstrated that if the remaining portion of the breast does not receive radiation therapy, the risk of recurrence is almost 50%.
For this reason radiation therapy is absolutely necessary after breast conservation therapy, in order to destroy possible foci of cancer cells located outside the tissue that has been removed.
What are the most common side effects of radiation therapy?
The most common side affects are: swelling and heaviness in the breast, sunburn-like skin changes in the treated area, and fatigue. These changes in the breast tissue usually disappear 6 to 12 months later. In some women, the breast becomes smaller and firmer after radiation therapy. Irradiation of the axillary lymph nodes (in the armpit) can also cause lymphedema.
Which is best, mastectomy or breast conservation therapy?
The main advantage of breast conservation therapy is that it saves the breast. The disadvantage: most women have to be given radiation therapy for several weeks.
Women who chose breast conservation therapy have the same survival rates as those who chose mastectomy. In the case of conservative breast therapy, local reincidence is higher. But these can usually be successfully treated by removing the entire breast.
We recommend that breast conservation therapy be used whenever possible.
These procedures are not used to treat cancer but they are useful for restoring the appearance of the breast after mastectomy. The breast can be reconstructed at the same time as the mastectomy (immediate reconstruction) or at a later time (delayed reconstruction). The surgeons may use implants or tissue from other parts of the body.
How do the patient and her doctor decide the type of reconstruction and when it will be done? The answer depends on each woman’s personal preferences and on the details of her medical situation, such as how much skin has been removed and if she has to undergo chemotherapy and/or radiation therapy.
Chemotherapy can delay reconstruction until after it is completed and radiation therapy affects the elasticity of the skin.
Above all, it must be kept in mind that breast reconstruction is a complex process, which attains very good results, but the breast will not be exactly the same it was before.
Its basic purpose is to recover the physical harmony that has been changed by the mastectomy and re-establish the emotional balance of the patient.
Being able to do the reconstruction immediately after mastectomy depends on several factors (personal choice of the patient, her emotional state, her expectations, her general health, and the size and shape of her breasts). Also the availability of surgical facilities must be considered because immediate reconstruction means the operation will take longer. The advantage of this procedure is that the patient avoids the experience of having just one breast.
Also, there are various ways to carry out reconstruction. For this reason the plastic surgeon, who forms part of the cancer care team, must inform the patient about the advantages and disadvantages of both immediate and delayed reconstruction, and of all the options available.
A woman who has been given the correct information can and probably should make her own choice, based on her doctor’s opinion.
So, what are the varieties or methods of reconstruction available nowadays?
There are two main options: the first one, and the most traditional, is the use of implants, that is, materials that do not come from the body (alloplastic materials); and the second is based on the use of tissue from the patient’s own body (skin-fat-muscle), which are called flaps.
Please explain the possibilities of implants.
In 1962 in North America silicon was put on the market, a material that can be used for woman who have had mastectomies, or for solely aesthetic purposes. But the use of this material has always been controversial because of safety concerns.
Silicone is a polymer (a large molecule, or macro-molecule, formed by the union of smaller molecules called monomers) that is odorless and colorless, and is mainly composed of silicon.
The most frequent problems are the prosthesis breaking or exploding, leakage, the shrinking of the capsule that contains the silicon, and various adverse reactions (pain, allergy, arthritis, asthma, chronic fatigue, fever, weight loss, headaches, deformation of the breast, bruises, bleeding) Many of these problems are attributed to the reaction of the auto-immune defense system against any foreign body, in this case, silicone.
There was also a controversy about the possibility of silicone causing breast cancer, in this case when used for breast enlargement.
However, an major Swedish study, following 3,500 woman for 37 years, found no increase in the incident of breast cancer among women who had had silicone implants. However, doubts have been raised about this study. One expert, Diana Zuckerman, of the National Research Center for Women and Families, warned that the fact that the study was financed by an important manufacturer of implants might have influenced the results. This expert claimed that there is no consensus about the safety of silicone implants. A declaration by the FDA (Food and Drug Administration), hopefully definitive, is expected.
Candidates for breast reconstruction should have this information so that they can decide freely if they want to use implants made of this material. Nowadays silicone prosthesis contain a denser, more cohesive substance, much less susceptible to leakage. Since the year 2000, they have been made of several layers of silicon, with substances that keep the gel in place between these layers.
A second possibility is using an expander, recommended when the skin isn’t sufficient elastic. In these cases a gradual stretching of the skin and the underlying tissues (basically fatty tissue) is essential. A bag or tissue expander is inserted and then is gradually filled with saline solution. This process takes a few months. The biggest inconvenience is that repeated visits to the doctor are required to attain the desired results. Sometimes the patient experiences discomfort or pain. Complications that have been reported are shrinking of the capsule, infections, and problems with the expander valve
And reconstruction using the patient’s own tissue?
The most widely-known is the TRAM (from “transverse rectus abdominis muscle”, since it uses the muscle of the front abdominal wall). A flap with skin and fatty tissue from this muscle is moved to the chest. Thus, the breast can be reconstructed without the introduction of foreign bodies. When the tissue is removed from the stomach, excess fat can also be removed, if necessary. It is not a simple procedure. It requires general anesthesia. A scar is left on the lower part of the abdomen.
One disadvantage of TRAM is that many women develop weakness in the abdominal wall, in the place where the flap has been removed from. The contents of the abdomen put pressure on the weak spot in the wall, giving rise to deformations that can occasionally cause problems, and may need corrective surgery (incisional hernias).
This problem was one of the motives for the development of a new technique, DIEP (Deep Inferior Epigastric Perforator). This is the latest technique of breast reconstruction. Only skin and fatty tissue from the abdomen are used, with no muscle nor implants involved. Since no muscle is removed, this technique does not have the drawback of weakening the abdominal wall that TRAM has.
DIEP is a very delicate microsurgery technique. The procedure lasts from 6 to 8 hours. An average of 5 days hospitalization is required. Recovery is rapid.
One important aspect is that the breasts (both) have a similar evolution. They grow thinner and fatter at the same time, and both age at the same rate as the body.
The final phase of breast reconstruction is nipple and areola reconstruction. This can be done once sufficient time has passed after the breast reconstruction surgery. This is a simple procedure that doesn’t require hospitalization. It is done with a local anesthesia.
Could you please define the concept of systemic therapy?
Systemic or general therapy is based on the application of medicines which act on the entire organism, since they are administered by mouth (via oral) or through the vein (via intravenous)
What are the procedures involved in systemic therapy?
1. The systemic therapy given to patients after surgery is called adjuvant (or complementary) therapy. The goal of adjuvant therapy is to kill hidden cancer cells. Even in the early stages of the disease, cancer cells can leave the breast tumor and spread through the blood stream to other parts of the body. These cells do not result in symptoms that can be detected, they can’t be seen in x-rays, nor can they be felt in a physical examination.
But they can establish new tumors in other organs or in the bones
This type of treatment is given only in cases where statistics show that there is a high risk of the cancer cells deposits described in the preceding paragraph. In these cases, post-surgical complementary therapy has been shown to be an important line of progress.
2. At times oncologists give their patients adjuvant therapy–that is, systemic therapy before surgery. In this case, the treatment is designed to reduce the size of a tumor that is too big to be removed. Or to reduce the size of the tumor so that breast conservation therapy may be used. Another of the advantages of neoadjuvant chemotherapy is that it’s possible to evaluate by touch or with a mammogram if the treatment has been effective or not. Effectively, a reduction in the size of the tumor is the best indication of the effectiveness of the neoadjuvant therapy.
3. Another form of systemic therapy is that given to patients with metastasis.
What drugs are used in systemic therapy?
The two most widely used types of therapy are hormone therapy and chemotherapy. Chemotherapy consists of administering drugs that stop the tumor from growing, by interfering in one of the stages of cell growth. Cells reproduce by dividing (mitosis). The cycle of cell division has the following stages: G1, or after cell division; S, or when the DNA is being replicated; G2, or the transition stage between the S-phase and mitosis, and the M-phase, or mitosis. Anti-cancer drugs have an effect on one or more of these stages.
Hormone therapy has been used since the hormone dependency of some tumors was demonstrated by Doctor Beatson in 1896 and Doctor Huggins in 1941, which makes it possible to block the growth of a tumor either temporary or permanently by using opposing or anti hormones. Regarding breast cancer, a good percent of the cases are hormone dependent.
What is hormone therapy?
It is a palliative treatment that is effective in the case of hormone dependent tumors A tumor is hormone dependent when its hormone receptors are positive.
First we will talk about additive hormone therapy, or hormonal therapy using drugs. For this kind of treatment, knowing about hormone receptors is crucial.
Could you explain what hormone receptors are?
They were discovered in 1970 by Doctor Jensen. This was an enormous advance. Effectively, the treatment strategy is determined by the presence of estrogen or progesterone receptors, since the response to therapy is related to the number of positive receptors the tumor has.
The receptors are located in the cell membrane (remember that the structure of a cell is like that of an egg, with a nucleus, a liquid component—cytoplasma—and an external covering or membrane).
They are like microscopic chemical hooks. They are designed to receive female hormones produced by the ovaries. Before her first menstruation, a girl’s breasts have hardly begun to develop. When she begins to menstruate (menarquia), her breasts begin to develop gradually. This is due to the effect of the ovarian hormones.
In order for the ovarian hormones to stimulate the breast cells to multiply, they need the help of the hormone receptors.
When the ovarian hormones reach the inside of the cells, what they do is attach themselves to the hormone receptors. Thus, the new biochemical body that is formed (hormone + receptor) moves to the nucleus. It carries the message to begin cell division to the DNA. The multiplying of cell divisions causes the formation of the adolescent breast, and later the adult one.
When a tumor forms, there are two types with regards to the hormone receptors. Some have contain receptors in their cells, and thus are more like normal cells. They are called hormone receptor positive.
But there is a second kind of tumors that have lost the receptors during growth.
This means there are two types of tumors. The former are hormone influenced or hormone dependent. The latter are hormone independent, which, regarding systemic therapy, only respond to chemotherapy.
This has significant therapeutic consequences. Hormone independent tumors can be treated with either receptor inhibitors (tamoxifen, raloxifene) or with drugs that can stop estrogen formation (such as the ones called aromatase inhibitors, anastrazole, letrozole),
What drugs are available for hormone therapy?
Estrogens, hormones produced by the ovaries, stimulate the growth of some types of breast cancer.
Doctors use different approaches to blocking the effects of estrogen or lowering its level. The most commonly used antiestrogen drug is tamoxifen, taken daily in table form for five years.
Various studies show that tamoxifen can reduce the possibility of recurrence after surgery (it also helps women with early breast cancer, regardless of their age)
Also, patients can use tamoxifen to treat breast cancer with metastasis.
At what dosage and for how long is tamoxifen usually prescribed?
After many studies it has been determined that the most effective dose is 20 milligrams per day for 5 years, as systemic therapy after surgery. If it is a case where the cancer has spread, this dosage is maintained as long as the tumor responds (that is, disappears or becomes smaller; if it begins to grow again, the hormone therapy must be changed).
What are the most common side effects of tamoxifen?
The most frequent are hot flashes, weight gain, irregular menstruation, problems with blood circulation (increase in varicose veins, thrombophlebitis) and an increased risk of uterine cancer.
What precautions should be taken to prevent–to the extent that is possible–these side effects?
Of course drugs containing estrogens cannot be taken to fight hot flashes Sometimes certain sedatives, requiring a doctor’s prescription, can help. As far as weigh gain goes, follow the Mediterranean diet and watch your weight. During hot weather, circulation problems can be prevented with acetylsalicylic acid (aspirin), at least mild cases, especially varicose veins.
Because of the increased risk of uterine cancer the gynecologist must be seen twice a year. The gynecological checkup will determine if there are any suspicious changes in the uterine wall. If changes are observed, a biopsy is carried out to determine if the treatment can be continued or not. One possible alternative to tamoxifen is Raloxifene, which has a similar degree of efficiency, but without the risk of uterine cancer However longer term studies are needed to determine if raloxifen does have the same efficiency in preventing breast cancer and in the treatment of metastasis as tamoxifen.
The cases with spread have decreased with respect to localized ones. When deciding the treatment for women with breast cancer that has spread, the therapist should not only think about the post treatment survival rate, but also about the quality of life of the survivor and the therapeutic morbidity rate, including considerations of side effects and the psychological and socio-economical situation of the patient and their family.
What other hormonal drugs are used in systemic therapy for breast cancer?
The second generation of aromatase inhibitors are very effective.
Aromatase inhibitors using circulating androgens block 90% of the estrogen production in postmenopausal women or in premenapausal women who have had their ovaries removed or suppressed by radiation therapy (see below). This way the fundamental effect of eliminating estrogens is attained.
What are the aromatase inhibitors available for use in humans?
To begin with, it should be pointed out that the current inhibitors are called second generation inhibitors, because the first generation was aminoglutentimid, a drug that is seldom used nowadays. Aminoglutetimid was effective, but it was too toxic.
The current inhibitors are anastrazol, letrozol and vorozole (the last one mentioned is still undergoing clinical trials and is not available yet).
Various studies have demonstrated that anastrazol and letrozol have a similar level of efficiency, and are best used in cases that are resistant to treatment with tamoxifen. However, some recent studies give grounds to believe that both can compete with tamoxifen as the best hormonal drug.
Could you explain the characteristics and possible side effects of anastrazol?
It is an aromatase inhibitor that is 200 times as powerful as aminoglutetimide. It does not affect the adrenal glands, as aminoglutetimide did, so it does not need to be accompanied by corticosteroids. A dosage of 1 milligram per day provides maximum blocking of aromatase and suppression of estrogens.
It is generally well-tolerated. It can produce hot flashes, vaginal dryness, headaches, and hair weakness. It can also produce gastrointestinal disruptions (loss of appetite, nausea, vomiting, and diarrhea). During the first weeks of treatment it can cause vaginal bleeding. Sometimes it can cause problems with blood circulation, such as thromboembolisms.
It does not increase the risk of uterine cancer.
It is an aromatase inhibitor that is 180 times as powerful as aminoglutetimide. It does not need to be accompanied by corticosteroids either. It is a powerful inhibitor of aromatases and estrogens. It is beginning to be recommended as a first line treatment, rather than tamoxifen.
The dosage is 2.5 milligrams per day.
It is generally well-tolerated. The most commonly-observed side effects are hot flashes, nausea, and hair weakness. It can also cause headaches, thrombophlebitis, vaginal bleeding in the first weeks of treatment, and weight loss or gain (depending on the individual).
It does not increase the risk of uterine cancer.
They reduce the levels or amounts of estrogens in the bloodstream. In the past they were used when the tumor became resistant to tamoxifen, but nowadays they have been substituted by aromatase inhibitors.
But one of them, medroxyprogesterone, is used in the supportive care of patients with breast cancer. Apart from reducing the level of estrogens, it plays an important role in maintaining patients’ quality of life, since it greatly improves their appetites.
And ablative hormone therapy ?
This is known as endocrine surgery. This involves the removal of the endocrine organs (especially the ovaries) to drastically reduce the amounts of female hormone produced.
Is this procedure still being used?
The surgical removal of the ovaries (oophrectomy) reduces the amount of estrogens produced. It has been used in the treatment of metastatic breast cancer in premenapausal women or as a preventive measure after localized breast treatment. It can be done through surgery or radiotherapy.
Nowadays, although this technique is still being used on women with very aggressive cases of breast cancer that are resistant to the most common treatments, the ant estrogen drugs that have been described previously (tamoxifen, anastrazol, letrozol) are used to obtain similar results with fewer complications.
When is hormone therapy indicated?
In the following situations:
A) Complementary or adjuvant hormone therapy, used in a similar way to that of chemotherapy after surgery. This can only be used with women who have hormone receptor-positive breast cancer.
B) Hormone therapy in cases of metastasis. Treatment of women with metastatic breast cancer. Positive hormone receptors must be present in these cases as well.
When is chemotherapy indicated?
In the following situations:
1. Patients with localized breast cancer with no known metastasis. There are three possibilities:
A) Chemotherapy before surgery, to try to reduce the size of large tumors so they can be removed. In many cases this even allows breast conservation therapy, if this is what the patient wants. At the same time it can destroy possible foci of invisible cells that are located outside the breast tumor.
B) Neoadyuvant chemotherapy, also applied before surgery, but with tumors that can be removed as they are. This treatment is also used in order to determine directly the effectiveness of chemotherapy. It also destroys cancer cells outside the breast tumor.
C) Complementary or adjuvant chemotherapy. Removing the breast cancer does not always eliminate all the cancer cells in the body, which can later develop into metastatic foci. Complementary chemotherapy should be applied immediately after surgery.
D) Patients with diagnosable macroscopic metastasis.
What anti-cancer medicines are effective in breast cancer?
Cyclophosphamide, adriamicine, methotrexate, 5-Fluoruracil, paclitaxel, doxetacel, camptotecine, vinorelbine, mitoxantrone, HN2, oncotiotepa, cisplatin and carboplatin. Another line of treatment is with trastuzumab.
Could you please describe them one by one?
Yes. We’ll begin with cyclophosphamide, which belongs to the group called alkylating agents. It is effective administered in pill form, intramuscularly or intravenously. A wide range of dosage is used. It is part of the most effective protocols of combined chemotherapy (see below), such as CMF and FAC. It has also been used in the high-dose chemotherapy with autotransplant strategy.
The most important side effects are nausea and vomiting, hair loss (alopecia), leukopenia (a decrease, usually temporary, of white blood cells), acute cystitis (painful urination), sometimes with blood in the urine, amenorrhea (lack of menstruation), and azoospermia (a reduction in the number of sperm cells).
A wide range of dosage is used. There are no limits to the amount that can be taken.
It is an antibiotic with antitumor properties. It is administered through the vein (intravenously). It is part of the FAC and AC protocols, widely used in treating breast cancer.
Its most serious side effects are alopecia, nausea and vomiting, medullar hyperplasia and aplasia (when the production of blood components is reduced or stopped at the level of the bone), stomatitis ulcerosa (irritation and ulcers in the mucus lining the mouth and digestive tract), and cardiac toxicity.
Cardiac toxicity is the principle problem of this medicine and limits the dosage . Before administration, a resting gated blood pool scan is carried out (a test that evaluates the pumping capacity of lower left ventricle (chamber) of the heart). If the result is normal, adriamycin can be given. The gated blood pool scan must be repeated periodically in order to make sure that the pumping function of the left ventricle is not adversely affected.
The dosage per series is usually 75 milligrams per square meter of patient. However, when it is administered with other anticancer drugs, the dosage is lowered slightly. A total dosage of 560 milligrams per square meter, or 450 milligrams per square meter if the patient has had radiation therapy to the chest, can not be exceeded.
Are there other drugs similar to adriamycin that are also effective in treating breast cancer?
Yes, for example, epidoxorubicin. It is quite similar to adriamycin, and thus is cardiotoxic. It does have the added advantage of permitting higher doses than adriamycin.
Another drug in this group is mitoxantrone, which has a structure similar to adriamycin and epidoxorubicin, but with lower cardiac toxicity.
What can you tell us about methotrexate?
It is a member of the antimetabolites, substances with a very similar structure to the metabolites that the cell uses to function normally and also in cell division. Antimetabolites have changes in their structure that trick the cell, which uses them and dies.
It is usually given via endovenous, although it can be given orally or intramuscularly. It is part of the CMF protocol.
Its main side effects are ulcero-necrotic stomatitis (irritation of the mucus lining the mouth and digestive track, with possible formation of ulcers that can become quite serious), myelopoeitic hyperplasia, bronchial fibrosis (hardening), liver and kidney toxicity.
A wide range of dosage is used. When combined with other drugs, the dosage usually ranges from 40 to 60 milligrams per square meter.
Let’s move on to 5-Fluoruracil.
More widely known as 5FU, it is one of the antimetabolites. It is administered through the vein (intravenously). It is part of the CMF and FAC protocols.
Its most serious side effects are nausea and vomiting, diarrhea, myelopoeitic hyperplasia (of the production of blood), alopecia, and hyperpigmentation of the skin in the veins where it is administered (to prevent this from happening, protect the limb from light).
When it is administered alone, the dosis is 15 milligrams per kilogram per day, for five days. In combination with other anti-cancer drugs, a dosage between 400 and 600 milligrams per square meter is used.
Is it true that anti-cancer drugs have been obtained from a tree, the yew or taxus brevifolia?
It is well known that trees and plants in general are one of the biggest sources of medicine in general and in anticarcinogens in particular.
The first anti-cancer drug obtained from the yew was paclitaxel, which interfers with cell division and with normal cell activities involving a microcorpuscle, the microtubules. Paclitaxel keeps these microtubules from breaking down and thus prevents cell division.
Paclitaxes has proved effective in treating breast cancer, in cases of metastasis and in chemotherapy after surgery In this aspect it is considered nowadays the most efficient protocol for women who are lymph node positive or hormone receptor negative is to administer four cycles of FAC, followed by four of paclitaxel. It is also effective in patients with breast cancer that has been treated previously with adriamycin based protocols and proved resistant (that is, failed to respond) to that drug.
The most common side effects are reduction of the blood production of the bone marrow or mielodepression, with a possible lowering of white blood cells, platelets, and red blood cells; affectation of the peripheral nervous system ( periferic neuropathy) with tingling in the fingertips and toes and possible numbness in the palms of the hands and soles of the feet; alopecia (temporary hair loss); alteration of mucous membrane (mucositis) and allergic reactions, which can be severe (although nowadays this is prevented by drugs given before paclitaxel is administered).
It is another taxane, similar to docetaxel, also effective in treating breast cancer. Its applications and effectiveness are similar to the other taxane.
As far as side effects go, they are similar to those described for parclitaxel.
It is obtained from an ornamental plant, vinca rodea, that also provides two other drugs used in cancer treatment (vincristin and vimblastin).
Combined with Ptorafur, it is effective in metastasized breast cancer. Its main side effects are reduction of leukocytes and/or platelets, nausea and/or vomiting, and liver dysfunction.
This is a drug that has recently become available and is effective in beast cancer patients with metastasis. In fact, it is not really an innovation, since it has a similar action in the tumor cell as that of 5-Fluoruracil. The side effects of capecitabine are also similar to those of 5-Fluoruracil.
That it can be administered by mouth is also nothing new, given that other derivatives of 5-Fluoruracil (for example, Ptorafur) that are also effective when taken orally.
What uses in breast cancer do HN2, oncotiotepa, cisplatin and carboplatin have?
They, like cyclophosphamide, belong to the group of alkylating agents. Administered independently, they are not very effective against breast cancer.
But they have been used in the high-dose chemotherapy with autotransplant strategy.
What is trastuzumab and what does it do?
In some cases of breast cancer, high levels of a certain protein, HER2/neu, are detected. This protein is designed to receive tumoral growth factors, which are codified in the HER2 oncogene.
Trastuzumab is a monoclonal antibody that attaches to the HER2 oncogene and block it from receiving those growth factors. As a result, positive responses can be obtained in metastatic tumors.
In breast cancer, transtuzumab has been shown to be effective in women with metastasis.
One essential condition is that the tumor must be HER2 positive. This is done by a lab test. The results of the test are expressed as negative or positive. If it is positive, it is called ‘positive with one or two crosses’ (+ or ++) or three crosses (+++), depending on the number of positive receptors. Only women that are HER2/neu+++ are candidates for treatment with trastuzumab.
Trastuzumab can be combined with other anti-cancer drugs, like paclitaxel, strengthening their respective effectiveness.
One of the side effects of trastuzumab is cardiac toxicity, which increases if it is combined with other anti-cancer drugs that are also cardio toxic, such as adriamycin. These two drugs must never be used together.
Various studies have tried to evaluate the effectiveness of trastuzumab combined with chemotherapy in stages of breast cancer with no metastasis.
BREAST CANCER TREATMENT ACCORDING TO STAGES
STAGE 0 There are two kinds:
1. Lobular carcinoma in situ. The risk for this type becoming invasive cancer is between 20 and 25% of the cases 15 years after it is diagnosed. It can affect both breasts. The treatment options are: bilateral mastectomy, a biopsy with close follow-up, or participating in a chemoprevention clinical trial.
2. Lobular carcinoma in situ. Breast conserving therapy is usually indicated (removal of the tumor and radiation therapy to the breast area).
The risk of the axillary lymph nodes being affected is very low (between 1 and 2% of the cases), so they are not usually removed. However, cases with a large tumor that requires mastectomy, when microscopic invasion is suspected, with a palpable tumor or with lymph node or vascular invasion, must be considered cases with risk and a sentinel lymph node biopsy should be carried out.
STAGE I. These are candidates for breast conservation therapy (see contraindications in the ‘Treatment’ section). The analysis of the axila is carried out by means of a sentinel lymph node biopsy.
Treatment after surgery. If the tumor is less than 1 centimeter in diameter, the risk of recurrence is less than 10%. No treatment is needed after surgery.
On the other hand, if the tumor is more than 1 centimeter, chemotherapy after surgery is indicated (in general CMF or AC protocol, when is described in “Treatment by chemotherapy”) followed, in general, by tamoxifen for five years if the hormone receptors are positive. If they are negative, only chemotherapy is applied.
STAGE II This stage can be treated by breast conservation therapy or a mastectomy, with identical results, so the option chosen depends on the size of the tumor, the anatomical characteristics of the patient, and her preferences.
For tumors that are between 4 and 5 centimeters, neoadjuvant, or presurgical, chemotherapy is preferred. Generally an adriamincyn based protocol is administered. The reduction in the size of the tumor in many cases allows breast conservation therapy, or of course mastectomy if the patient wishes.
Radiotherapy is always administered after breast conservation therapy. But in the cases of mastectomy where the tumor is larger than 3 centimeters, the surgical margins are not cancer free, or if there are four or more axillary lymph nodes are involved, radiotherapy after surgery should be considered, above all in the area of the mastectomy and the armpit. This improves disease-free survival and the overall survival rate.
Treatment after surgery. All the patients in stage II must receive treatment according to the following scheme:
Women under 49. Chemotherapy reduces the mortality rate by 25 to 30%. 4 to 6 courses of CMF, A-CMF, FAC or CAF (see description) can be given.
Another protocol proposes 4 courses of AC followed by 4 or paclitaxel.
1. Women 50 years and older. There are two groups.
*Hormone receptor positive. Tamoxifen taken for 5 years reduces the mortality rate by 20%. In post menapausal women, anastrazol or another aromatase inhibitor can be considered.
*Hormone receptor negative Chemotherapy, with one of the protocols mentioned for women under 49.
COMMON CHEMOTHERAPY PROTOCOLS
They are the following:
CMF cyclophosphamide, methotrexate and fluorouracil .
FAC fluorouracil, doxorubicin, cyclophosphamide.
AC: adriamycin and cyclophosphamide
AC followed by paclitaxel. 4 cycles of paclitaxel are given after 4 cycles of AC.
AC and trastuzumab.
AT adriamycin and docetaxel.
Vinorelbine and tegafur
Vinorelbine and trastuzumab.
Trastuzumab and paclitaxel.
MONOTHERAPY (single drug)
STRATEGIES AND BASIS FOR ADMINISTERING CHEMOTHERAPY
The military term ‘strategy’ came into use in antineoplastic chemotherapy (AC) when several experiences showed that the greater efficiency of this branch of treatment depended fundamentally on the way that the anticancer drugs were administered.
Single drug chemotherapy has been replaced by combined chemotherapy (the use of various drugs at the same time), with better results. These drugs are combined following the criteria established by doctor Carter years ago.
The drugs that are combined must have different mechanisms of action and different toxicity.
Each one of the drugs used must be applied at the maximum tolerated dosage.
As far as possible a combination with synergetic effects are sought (that strengthen each other’s effects).
Along with combined chemotherapy, the basis of chemotherapy in localized cases are the concepts that have been explained in the sections on presurgical chemotherapy, neoadyuvant chemotherapy, and complementary chemotherapy. And combined chemotherapy in advanced cases, the strategy in breast cancer with metastasis.
And high-dose chemotherapy with autotransplant?
The use of high dosage (perhaps it would be better to say extremely high) is also called intensive chemotherapy, and, following doctor Livingston, is used to refer to those cases that require hospitalization of the patient in order to provide support care.
In fact, auto transplant strategies are not carried out routinely; only patients participating in clinical trials receive this treatment.
The reason for this is that so far there is no evidence that this expensive and risky technique is more effective than the chemotherapy protocols currently in use.
So what sort of support care are you referring to?
Above all hematological resources, such as growth factors and erythropoietin.
For many years mielodepression (reduction of the production of the parts of blood by the blood marrow myelopoetic–don’t confuse with the spinal cord, which transmits nerve impulses) has been one of the main problems to be dealt with when administrating anti cancer drugs.
There are many negative consequences of mielodepression: The reduction in numbers of white blood cells and/or platelets is accompanied by delays in the administration of chemotherapy, infections and/or hemorrhaging, and secondly, by disruptions in the quality of life of the patients.
The reduction in the number of hematites (red blood cells) causes anemia, with a loss of appetite, weakness, loss of energy, etc.
In the last few years much has been learned about hemopoyesis (the process of producing the components of bloods) The so called hematological growth factors have also been discovered. The most well know and used as support for chemotherapy are:
Granulocyte c olony-stimulating factors (a part of the white blood cells that is fundamental in the prevention of and fight against infections).
*Nowadays, filgrastim, pegfilgrastim, and macrophage stimulating factors are used.
*Human erythropoietin, essential for the production of hematites. Epoetin alfa and EPO are available.
As treatment support for chemotherapy, these drugs have the following uses:
Granulocyte growth factors:
1. Preventative uses. In preventing the reduction in the number of granulocytes and subsequent risk of infections in patients that have shown to be at high risk from secondary infections in chemotherapy.
2. Therapeutic uses. Growth factors are administered if the number of granulocytes fall or if there is a secondary fever.
These are not used in all patients, just those with a high risk of infection. For most patients, reducing the dosage or postponing chemotherapy allows the white blood cells (and the granulocytes) to return to their normal levels. Limiting the use of growth factors is important, since they are very expensive.
Its main use is in treating secondary anemia caused by chemotherapy. This kind of anemia is not very common in breast cancer patients, except those taking adriamycin, or in an advanced stage of the disease.
What erythropoietin does is reduce the need for blood transfusions.