Breast Cancer Chapter 12
Types of Breast Cancer Treatment
There are four standard types of treatment for breast cancer patients: surgery, radiation therapy, chemotherapy, and hormone therapy. While treatment regimens may vary, the important constants are to communicate closely with the care team, understand treatment options, and maintain the treatment regimen. (Note: The following methods of breast cancer treatment are common to the US; different treatment techniques may be used in other countries.)
For most patients with cancer, the main treatment is surgery to remove the cancer from the breast. In deciding which form of surgery is most appropriate, the surgeon will consider the size and type of the tumor, the stage of the cancer, and lymph node involvement, along with the age and health of the patient. Breast-conserving surgery removes the cancer but not the breast itself. Mastectomies remove the entire breast.
Breast-conserving surgery can be a lumpectomy or a partial mastectomy.
- Lumpectomy removes the tumor and a small amount of the normal tissue around it. Several lymph nodes may be removed as well.
- Partial mastectomy (also called segmental mastectomy) removes the tumor and a larger amount of breast tissue, along with some skin and the lining over the chest muscles below the tumor. This surgery is usually performed for Stage 1 and 2 tumors.
In breast-conserving surgery, some of the axial lymph nodes may be removed for biopsy (called lymph node dissection). This may be done at the same time as the surgery or after. The lymph node dissection is done through a separate incision.
There are several different forms of mastectomy:
- Total mastectomy (also known as simple mastectomy) removes the entire breast, but the lymph nodes and the surrounding muscle are left intact.
- Modified radical mastectomy is the most common surgical procedure performed for breast cancer. The entire breast, the axial lymph nodes, and the lining over the chest muscles are all removed, but the muscles are left intact.
- Radical mastectomy is seldom performed. The breast, lymph nodes, chest muscles under the breast, and some of the surrounding fatty tissue are removed. Radical mastectomy is done in cases of extensive tumors and when cancer cells have invaded the chest wall.
- Subcutaneous mastectomy removes the tumor and breast tissue, but the nipple and the overlying skin are left intact. This makes breast reconstruction easier, but some cancer cells may remain.
- Skin-sparing mastectomy is a relatively new surgical technique. The surgeon makes a small "keyhole" incision around and near the areola. The same amount of breast tissue is removed as would be in traditional forms of mastectomy, but scarring is negligible and 90% of the skin is preserved. Reconstruction is performed during the same operation by a plastic surgeon, using tissue from the patient's abdomen or back.
Survival rates aren't significantly different between simple mastectomy plus lymph node dissection and breast-conserving surgery plus radiation therapy, so patient preference is an important factor in deciding which treatment to use.
After the Surgery
Surgery usually seeks to remove all the cancer that can be seen during the operation, but some cancer cells may still be left. In order to kill the remaining cancer cells, the patient may be given radiation therapy, chemotherapy, or hormone therapy. This is called adjuvant therapy.
Side Effects of Surgery
Possible side effects include postsurgical pain, wound infection, hematoma (buildup of blood in the wound), and seroma (buildup of clear fluid in the wound). If axillary lymph nodes are also removed, the main long-term effect is lymphedema (swelling of the arm), in which excess fluid builds up in the arm.
Radiation therapy is done to kill any cancer cells that remain in the body after surgery. There are two formsof radiation therapy: external and internal (brachytherapy).
External Radiation Therapy
This is the most common type of radiation therapy for breast cancer treatment. The goal of external radiation therapy, also known as radiotherapy, is to irradiate a targeted area while avoiding surrounding tissues. Radiation damages a cell's DNA. If the irradiated cell divides before it can repair the damage, that cell will die. Because cancer cells divide more rapidly than healthy cells, healthy cells are better able to repair the damage done by the radiation.
Targeting a precise area is crucial to the success of radiation therapy. Breast radiation therapy typically lasts 6-7 weeks, a long enough period of time so that even the healthy cells repeatedly exposed to radiation can be damaged. That's why radiation therapy seeks, as much as possible, to irradiate only cancerous areas of tissue.
External beam radiation is given in small doses over a long period of time. Typically, patients receive radiotherapy once a day, 5 days a week (Monday-Friday) for 6-7 weeks. Receiving only a small dose of radiation every day helps to minimize the damage sustained by the healthy cells of the surrounding organs, and having weekends off helps the body to repair the damage done to it.
The extent of the radiation therapy depends on whether a lumpectomy or a mastectomy was done, and whether there is lymph node involvement. If a lumpectomy was performed, the entire breast receives radiation, and possibly the chest wall and lymph nodes as well. Radiotherapy is usually delayed until the tissues have had time to heal after surgery, about a month. If the patient is going to have chemotherapy, radiotherapy usually takes place after chemotherapy is finished.
In brachytherapy, or internal radiation, radioactive seeds or pellets are inserted into the breast tissue next to the cancer. Brachytherapy may be the only form of radiation administered, but more often it is done in conjunction with external radiation therapy. The size and location of the tumor, and other factors, limit who can receive brachytherapy. Some doctors still consider brachytherapy to be experimental: long-term results of brachytherapy are not yet available.
Types of brachytherapy:
- Intracavitary brachytherapy uses a small balloon attached to a thin tube. The deflated balloon is inserted into the cavity left after a lumpectomy and filled with saline solution. Twice a day a radioactive source is inserted into the balloon through the tube and removed after a short period of time. The treatment continues for 5 days, after which the balloon and tube are removed.
- Interstitial brachytherapy utililizes several catheters (small tubes), which are inserted into the breast tissue around the area of the lumpectomy. Radioactive pellets are inserted into the catheters, left for a short period of time, and then removed.
Image-Guided Radiation Therapy (IGRT)
Image-guided radiation therapy (IGRT) is a recent technology that helps radiation oncologists deliver radiation to the exact location of the tumor. Before IGRT, the tumor was located during the simulation phase of radiation treatment, and the site was marked with permanent ink or implanted metallic markers. These were used to define the area to be radiated in the actual radiation treatment sessions. But this wasn't a satisfactory method, because everyday activities and functions, like eating, drinking, and breathing, cause many tumors to shift their position between treatments. To compensate for this movement, oncologists radiated large margins of up to 2 cm of healthy tissue around the expected site of the tumor. This caused unwanted short-term and long-term side effects, including the possible development of other tumors. It could also prevent the delivery of adequate radiation doses to the tumor. Oncologists can now replace the traditional regiment of daily low-dose treatments over 6-10 weeks with several large doses delivered over a shorter time period.
Using IGRT, radiation oncologists can pinpoint the exact location of the tumor just prior to, and sometimes even during, each radiation session. IGRT uses ultrasound, CT scan imaging, or other imaging techniques that are integrated with the linear accelerator. The radiation team compares the images captured just before the treatment to those obtained during the simulation phase and adjusts the radiation beams as necessary.
Intensity-Modulated Radiation Therapy (IMRT)
Intensity-modulated radiation therapy (IMRT) is a recent technology that, like IGRT, precisely targets tumors and minimizes the radiation dose to adjacent areas. It does this by using multiple small beams of varied intensities instead of a single, large beam. The beams are "crossfired" at the tumor from different angles, enabling the radiation oncologists to deliver a high dose of radiation to the tumor while reducing damage to surrounding tissue.
IMRT may be used to treat tumors that were difficult to treat in the past, for example, tumors that have wrapped around the spine. IMRT enables such tumors to be treated with modulated intensity and precise targeting, sparing the delicate tissue and nerves near them.
Side Effects of Radiation Therapy
Side effects of radiation therapy include swelling, redness, and fatigue. In some women, the breast becomes smaller and firmer after radiation therapy. Having radiation therapy may also limit the chances of having breast reconstruction. Rarely, radiation therapy may damage the ribs. A very rare complication of radiation is the development of another cancer.
Systemic Breast Cancer Treatment:
Chemotherapy and Hormone Therapy
Systemic therapy targets cancer cells anywhere in the body, unlike radiation treatment, which targets one area specifically. Types of systemic therapy for breast cancer include chemotherapy and hormone therapy.
Cancer-killing drugs used in chemotherapy may be given intravenously or orally. Chemotherapy is done in cycles, with treatment periods followed by recovery periods. Treatment usually lasts for several months.
Chemotherapy may be given to the patient in several situations.
- Neoadjuvant chemotherapy is given before surgery to shrink large cancers so that they become small enough to be removed by lumpectomy instead of mastectomy.
- Adjuvant chemotherapy is used after surgery when there is no evidence of metastasis. It reduces the chances that cancer will recur, because it kills cancer cells that may have broken off from the primary tumor and traveled elsewhere in the body.
- Chemotherapy for advanced breast cancer can be the main treatment when cancer has metastasized.
Chemotherapy is most effective when combinations of more than one drug are used. Some of the most common drug combinations are:
- CMF: cyclophosphamide (Cytoxan), methotrexate (Amethopterin, Mexate, Folex), and 5-fluorouracil (Fluorouracil, 5-FU, Adrucil)
- CAF (FAC): cyclophosphamide, doxorubicin (Adriamycin), and 5-fluorouracil
- EC: epirubicin (Ellence) and cyclophosphamide
- TAC: docetaxel (Taxotere), doxorubicin (Adriamycin), and cyclophosphamide
- CEF (FEC): cyclophosphamide, epirubicin, and 5-fluorouracil (with or without docetaxel)
- GT: gemcitabine (Gemzar) and paclitaxel (Taxol)
Side Effects of Chemotherapy
Some of the most common side effects of chemotherapy include hair loss, mouth sores, loss of appetite, nausea and vomiting, increased chance of infections (due to low white blood cell counts), easy bruising or bleeding (due to low blood platelet counts), and fatigue (sometimes lasting for years). Less common side effects include menstrual changes, neuropathy (pain or tingling in the extremities), increased risk of leukemia, decrease in mental functioning, heart damage, and feelings of unwellness.
Chemotherapy and Hormone Therapy
Chemotherapy and hormone therapy are considered systemic therapies because they kill cancer cells anywhere in the body. Chemotherapy can be given before surgery to shrink large tumors, after surgery to kills cancer cells that may have broken off the main tumor, and as the main treatment for metastatic cancer. Hormone therapy can help reduce the chance that cancer will recur after surgery and may be used to shrink larger tumors.
Side effects of chemotherapy include:
- Loss of intestinal lining
- Loss of hair and skin
Treatment with Herceptin
HER2-positive tumors can be treated with trastuzumab (Herceptin), a type of monoclonal antibody. Monoclonal antibodies are laboratory-produced molecules that mimic the antibodies the body naturally produces. Herceptin attaches to the HER2 receptor and prevents human epidermal growth factor from reaching breast cancer cells, helping to stop their growth. Herceptin may also signal the body's immune system to destroy the cancer cell.
Herceptin is highly effective in reducing the risk of cancer recurrence in women with HER2-positive early-stage cancer, used in combination with or after chemotherapy. In women with metastatic breast cancer, Herceptin, in combination with chemotherapy, reduces the size of tumors distant from the original, slows the return of these tumors, and reduces the risk of their returning.
Another form of systemic therapy is hormone therapy. The hormone estrogen promotes the growth of about two-thirds of breast cancers, those that have estrogen receptors (ER-positive cancers) and/or progesterone receptors (PR-positive cancers). When cancerous breast tissue is biopsied, it is tested to see if either or both of these hormone receptors are present. If they are, then the cancer should respond to hormone treatment (more accurately termed hormone-blocking treatment). Women with hormone-receptive cancers have a better prognosis than women without these receptors.
Hormone therapy lowers the body's estrogen levels or blocks the effect of estrogen in order to stop cancer cells from growing. Like chemotherapy, hormone therapy is generally used as an adjuvant therapy to help reduce the chances that cancer will recur after surgery, but it may also be used for more advanced breast cancers to shrink and control the tumor.
Types of Hormone Therapy:
In premenopausal women, the ovaries are the main source of estrogen. Ovarian ablation can be performed surgically or with drugs. The surgical operation is called an oophorectomy, and it removes the ovaries permanently.
Alternatively, drugs called luteinizing hormone-releasing hormone (LHRH) analogs, such as goserelin (Zoladex) or leuprolide (Lupron), block the ovaries from producing estrogen.
In postmenopausal women, body fat and the adrenal gland, not the ovaries, are the main sources of estrogen. Two classes of medications are used for postmenopausal women: selective estrogen receptor modulators (SERMs) and aromatase inhibitors.
- SERMs block estrogen from attaching to the estrogen receptor on cancer cells. They are used in both pre- and postmenopausal women. The SERM most commonly used is tamoxifen (Nolvadex), and it is taken orally for up to 5 years.
- Aromatase inhibitors block the production of estrogen by cells other than the ovaries. Aromatase inhibitors include anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin), and are only effective in postmenopausal women.
- Fulvestrant (Faslodex) is an estrogen receptor antagonist. It works in two ways: it blocks estrogen receptors (like tamoxifen), and can also change the shape of estrogen receptors on cancer cells, so the estrogen can't attach to them. It is generally used for postmenopausal women with advanced breast cancer that no longer responds to tamoxifen.
Side Effects of Hormone Therapy
Tamoxifen may cause menopausal symptoms such as night sweats, hot flashes, and vaginal itching, discharge, or dryness. Rare but serious side effects, including blood clots and endometrial cancer, can occur. Aromatase inhibitors tend to have fewer serious side effects than tamoxifen, but can cause joint stiffness and/or pain as well as osteoporosis. The major side effects of fulvestrant are hot flashes, mild nausea, and fatigue.
Breast reconstruction may be done immediately after a mastectomy, or after treatment is completed, to make the breast about the same size and shape as it was before.
- Implant procedures using saline- or silicone gel-filled implants are the simplest and most common form of breast reconstruction. However, more than a third of women who have implant reconstruction must have a second surgery at a later date, mostly due to ruptures and infections.
- Tissue flap procedures use tissue from the abdomen, back, thighs, or buttocks to rebuild the breast. Two sets of scars are created: on the reconstructed breast, and on the area where the tissue was removed. With the exception of the DIEP flap, muscle tissue is used along with skin and fat tissue, which can result in weakness and muscle damage.
- TRAM (transverse rectus abdominis myocutaneous) flaps utilize tissue from the abdomen
- Latissimus dorsi flaps use tissue from the upper back
- Gluteal free flaps use tissue from the buttocks
- DIEP (deep inferior epigastric artery perforator) flaps are a recent innovation that use skin and fat, but not muscle, from the lower abdomen
- Nipple and areola reconstruction is optional and is usually done about 3-4 months after surgery. Tissue is taken from the new breast or from elsewhere in the body. Nipple-sparing mastectomies leave the nipple and areola in place while the breast tissue underneath is removed. Nipples can also be removed and saved for later reconstruction, but this is no longer widely done.
Breast cancer patients may decide to enroll in a clinical trial. There are both benefits and drawbacks to doing so.
What Is a Clinical Trial?
Clinical trials are scientific research studies, done with volunteers, that try to find improved ways to prevent, screen for, diagnose, or treat a disease. Clinical trials for cancer are very rarely done with placebos (nonactive drugs) the way some other types of trials are. In cancer clinical trials, new treatments are compared against the current standard of care (best treatment currently available).
Types of Clinical Trials
- Prevention trials test lifestyle changes and supplements or drugs that may lower the risk of getting cancer.
- Screening trials attempt to find the best ways of detecting cancer.
- Treatment trials test new treatments, for instance drugs, surgical techniques, combinations of treatments, or innovative treatments such as gene therapy.
- Quality of life trials (also called supportive care trials) try to find the best ways to make cancer patients more comfortable and improve their quality of life.
Clinical Trial Phases
Clinical trials are done in four phases:
- Phase I trials are the first time that substances being investigated are tested on human beings (usually, drugs are tested on lab animals first). Determining the safety and dose of the drug are the main objectives.
- Phase II trials study trials begin to evaluate whether the treatment is effective and continue to assess its safety.
- Phase III trials test the new treatment in comparison to the current standard of care. Phase III trials often enroll large numbers of people.
- Phase IV trials test a drug that has already been approved by the FDA and is on the market. Typically, Phase IV trials appraise new uses for the treatment, how it works, different doses, and new ways of administering it.
What Are the Pros and Cons of Enrolling?
The benefits of enrolling in a clinical drug trial can include:
- Access to a treatment that may prove to be more beneficial than other treatments that are currently available
- Helping to make a beneficial new treatment available to others who need it
- Trial sponsors often pay for volunteers' health care, incidental expenses, and time spent in the trial
There can be drawbacks to enrolling in a clinical trial, as well:
- The treatment may not work
- The treatment being tested may result in unpleasant side effects
- There may be financial complications: the study may not pay for volunteers' medical care, and insurers may deny coverage
How to Find a Trial
If you are interested in enrolling in a clinical trial, talk to your doctor. He or she may know of a clinical trial that's appropriate for you. If not, there are a number of clinical trials databases and matching services available online:
CenterWatch global database CenterWatch has a global database of clinical trials
The US National Institutes of Health database The US National Institutes of Health database includes trials being conducted in the US and around the world
EmergingMed database EmergingMed features a database for clinical trials in the US and Canada
The American Cancer Society clinical trials The American Cancer Society has a clinical trials matching service that includes trials being conducted in the US as well as some international trials
Even after a tumor has been surgically removed and the patient has had systemic treatment, some cancer cells can still remain in the body. In time, they may form new tumors. This is called recurrence. Recurrence can happen at the site of the original cancer, near that site, or in distant tissue or organs. Breast cancer can recur at any time, but it most often happens in the first 3-5 years after initial treatment. If recurrence is local, it can usually be treated successfully.
There are three main types of recurrence:
- Local recurrence. This is the most common type of recurrence, in which cancer cells that remain at the original site grow back over time. Local recurrence can happen even after mastectomy if cancer cells remain in the breast skin or fatty tissue. This type of recurrence is considered to be failure of the primary treatment.
- Regional recurrence. Regional recurrences can occur in the chest muscles and also in the lymph nodes below the breastbone, above the collarbone, and surrounding the neck. This is considered a more serious type of recurrence, because it indicates the cancer has spread.
- Distant recurrence. In distant recurrence, breast cancer metastasizes to distant organs and tissues, most often the bone, lungs, or liver. It can also spread to the brain and other organs. This is the most dangerous type of recurrence.
Who Is Most Likely to Have Recurrence?
Physicians use prognostic indicators to estimate who is most likely to have a cancer recurrence. Common indicators include:
- Lymph node involvement. If lymph nodes have been involved, recurrence is more likely.
- Tumor size. The larger the tumor, the greater the chance of recurrence.
- Hormone receptors. Tumors with hormone receptors tumors tend to be less aggressive and to respond more favorably to hormone treatment.
- Histologic grade. The higher the grade of the original tumor, the greater the chance of recurrence.
- Nuclear grade. This is the rate at which the cells divide to form new cells. Cells with a higher grade divide faster and are usually more aggressive.
- Oncogene expression. Oncogenes are genes that promote cancerous changes in a cell. The presence of certain oncogenes increases the chances of recurrence.
Early Detection Matters
For many years the evidence was inconclusive, but a recent, large-scale study has shown that early detection of recurring breast cancer greatly increases a woman's chance of surviving. In the study, if the second breast cancer was detected before symptoms appeared, chances of survival were improved by between 27-47%. This shows the importance of continuing to look for cancer after treatment and of catching it early, before symptoms (such as a lump) appear.
After treatment for breast cancer, women should continue to practice breast self-examination each month, checking both the treated area and the other breast. It's important to keep scheduled follow-up appointments where clinical breast exams and imaging tests will be performed. Follow-up appointments are usually scheduled every 3-4 months following treatment. The longer the patient remains cancer-free, the less often she will need to see her physician. Mammograms are usually scheduled once a year, but patients whose prognostic indicators show they may be at risk for recurrence should discuss the frequency and type of imaging tests they receive with their physician.
Imaging for Recurrence
A variety of imaging tests can be given to detect recurrent cancer early, including mammograms, MRI, CT, PET, and PET/CT. Of these, MRI is very accurate in detecting local recurrence. PET, and PET in combination with MRI and CT, are particularly useful in detecting recurrence and differentiating between scar tissue and recurrent cancer. PET in combination with MRI or CT can precisely locate tumors for purposes of radiation treatment or biopsy.
Because PET images biochemical activity, rather than structures, of the body, it is currently considered to be the most accurate diagnostic procedure to differentiate tumor recurrences from radiation necrosis (tissue death) or scar tissue, or postsurgical changes. It is also useful to combine PET with CT or MRI images, which show anatomical structures, so that the two modalities can be compared. For instance, lymph nodes may become enlarged due to cancer or for other reasons. CT and MRI images can reveal that the nodes are enlarged, but they can't reveal the cause. PET can reveal whether the enlargement is due to a tumor.
The addition of CT to a PET scan is also useful in locating the precise position of a mass for purposes of biopsy or radiation treatment. PET/CT machines are able to perform both types of scans at the same time. The PET scan detects the metabolic signal of actively growing cancer cells, and the CT scan provides a detailed picture of the patient's internal anatomy, revealing the location, size, and shape of the cancer.
Even after surgery and systemic treatment, some cancer cells can remain in the body. In time, they may form new tumors. This is called recurrence. Recurrence can happen in or near the original tumor site, or far away from it. If breast cancer recurs locally, it can usually be treated successfully.
Recurrent cancer can be detected using a number of imaging technologies, including mammograms, MRI, CT, PET, and PET/CT. PET scans show biochemical activity of the body. It is the best technology for telling apart new tumors and scar tissue caused by surgery or radiation.
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