General Types of Treatment

Treatments can be classified into broad groups, based on how they work and when they are used.

Local versus systemic therapy

Local therapy is intended to treat a tumor at the site without affecting the rest of the body. Surgery and radiation therapy are examples of local therapies.

Systemic therapy refers to drugs which can be given by mouth or directly into the bloodstream to reach cancer cells anywhere in the body. Chemotherapy, hormone therapy, and targeted therapy are systemic therapies.

Adjuvant and neoadjuvant therapy

Patients who have no detectable cancer after surgery are often given adjuvant (additional) systemic therapy. Doctors believe that in some cases cancer cells may break away from the primary breast tumor and begin to spread through the body by way of the bloodstream even in the early stages of the disease. These cells can’t be felt on a physical exam or seen on x-rays or other imaging tests, and they cause no symptoms. But they can go on to become new tumors in other organs or in bones. The goal of adjuvant therapy is to kill these hidden cells.

Not every patient needs adjuvant therapy. Generally speaking, if the tumor is larger or the cancer has spread to lymph nodes, it is more likely to have spread through the bloodstream. But there are other features, some of which have been previously discussed, that may determine if a patient should get adjuvant therapy. Recommendations about adjuvant therapy are discussed in the sections on these treatments and in the section on treatment by stage.

Some patients are given systemic therapy, usually chemotherapy, before surgery to shrink a tumor in the hope it will allow a less extensive operation to be done. This is called neoadjuvant therapy.

Surgery for Breast Cancer

Most women with breast cancer have some type of surgery. Surgery is often needed to remove a breast tumor. Options for this include breast-conserving surgery and mastectomy. Breast reconstruction can be done at the same time as the mastectomy or done later on. Surgery is also used to check the lymph nodes under the arm for cancer spread. Options for this include a sentinel lymph node biopsy and an axillary (armpit) lymph node dissection.

Breast-conserving surgery

In these types of surgery, only a part of the affected breast is removed, although how much is removed depends on the size and location of the tumor and other factors. If radiation therapy is to be given after surgery, small metallic clips (which will show up on x-rays) may be placed inside the breast during surgery to mark the area for the radiation treatments.

Lumpectomy removes only the breast lump and a surrounding margin of normal tissue. Radiation therapy is usually given after a lumpectomy. If adjuvant chemotherapy is to be given as well, radiation is usually delayed until the chemotherapy is completed.

Partial (segmental) mastectomy or quadrantectomy removes more breast tissue than a lumpectomy. For a quadrantectomy, one-quarter of the breast is removed. Radiation therapy is usually given after surgery. Again, this may be delayed if chemotherapy is to be given as well.

If cancer cells are found at any of the edges of the piece of tissue removed, it is said to have positive margins. When no cancer cells are found at the edges of the tissue, it is said to have negative or clear margins. The presence of positive margins means that that some cancer cells may have been left behind after surgery. If the pathologist finds positive margins in the tissue removed by breast-conserving surgery, the surgeon may need to go back and remove more tissue. This operation is called a re-excision. If the surgeon can’t remove enough breast tissue to get clear surgical margins, a mastectomy may be needed.

For most women with stage I or II breast cancer, breast-conservation therapy (lumpectomy/partial mastectomy plus radiation therapy) is as effective as mastectomy. Survival rates of women treated with these 2 approaches are the same. However, breast-conservation therapy is not an option for all women with breast cancer (see “Choosing between lumpectomy and mastectomy” below).

Radiation therapy can sometimes be omitted as a part of breast-conserving therapy. Although this is somewhat controversial, women may consider lumpectomy without radiation therapy if all of the following are true:

* they are age 70 years or older

* they have a tumor 2 cm or less that has been completely removed (with clear margins)

* the tumor is hormone receptor-positive, and the women is getting hormone therapy (such as tamoxifen or an aromatase inhibitor)

* no lymph nodes contained cancer

You should discuss this possibility with your health care team.

Possible side effects: Side effects of these operations can include pain, temporary swelling, tenderness, and hard scar tissue that forms in the surgical site. As with all operations, bleeding and infection at the surgery site are also possible.

The larger the portion of breast removed, the more likely it is that there will be a noticeable change in the shape of the breast afterward. If the breasts look very different after surgery, it may be possible to have some type of reconstructive surgery (see the section, “Reconstructive surgery”), or to have the unaffected breast reduced in size to make the breasts more symmetrical. It may even be possible to have this done during the initial surgery. It’s very important to talk with your doctor (and possibly a plastic surgeon) before surgery to get an idea of how your breasts are likely to look afterward, and to learn what your options might be.

Mastectomy

Mastectomy involves removing all of the breast tissue, sometimes along with other nearby tissues.

In a simple or total mastectomy, the surgeon removes the entire breast, including the nipple, but does not remove underarm lymph nodes or muscle tissue from beneath the breast. Sometimes this is done for both breasts (a double mastectomy), especially when it is done as preventive surgery in women at very high risk for breast cancer. Most women, if they are hospitalized, can go home the next day.

For some women considering immediate reconstruction, a skin-sparing mastectomy can be done. In this procedure, most of the skin over the breast (other than the nipple and areola) is left intact. This can work as well as a simple mastectomy. The amount of breast tissue removed is the same as with a simple mastectomy.

This approach is only used when immediate breast reconstruction is planned. It may not be suitable for larger tumors or those that are close to the skin. Implants or tissue from other parts of the body are used to reconstruct the breast. Although this approach has not been used for as long as the more standard type of mastectomy, many women prefer it because it offers the advantage of less scar tissue and a reconstructed breast that seems more natural.

Some doctors doing a prophylactic (preventive) mastectomy might consider doing a subcutaneous mastectomy. In this procedure, the incision is made below the breast. The breast tissue is removed, but the breast skin and nipple are left in place. This is followed by breast reconstruction. This procedure leaves less visible scars, but it also leaves behind more breast tissue than other forms of mastectomy, so the chances that cancer may develop in the remaining tissue are higher than for a skin-sparing or simple mastectomy. Because of the higher chance of cancer developing, most doctors do not recommend this procedure for women who opt for a preventative mastectomy.

A modified radical mastectomy is a simple mastectomy plus removal of axillary (underarm) lymph nodes. Surgery to remove these lymph nodes is discussed in further detail later in this section.

A radical mastectomy is an extensive operation where the surgeon removes the entire breast, axillary lymph nodes, and the pectoral (chest wall) muscles under the breast. This surgery was once very common. But a modified radical mastectomy has been proven to be as just as effective without the disfigurement and side effects of a radical mastectomy, so radical mastectomies are rarely done now. This operation may still be done for large tumors that are growing into the pectoral muscles under the breast.

Possible side effects: Aside from post-surgical pain and the obvious change in the shape of the breast(s), possible side effects of mastectomy include 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, other side effects may occur (see “Axillary lymph node dissection”).

Choosing between lumpectomy and mastectomy

Many women with early-stage cancers can choose between breast-conserving surgery and mastectomy.

The main advantage of a lumpectomy is that it allows a woman to keep most of her breast. A disadvantage is the usual need for radiation therapy — most often for 5 to 6 weeks — after surgery. A small number of women having breast-conserving surgery may not need radiation while a small percentage of women who have a mastectomy will still need radiation therapy to the breast area.

When deciding between a lumpectomy and mastectomy, be sure to get all the facts. You may have an initial gut preference for mastectomy as a way to “take it all out as quickly as possible.” Women tend to prefer mastectomy more often than their surgeons do because of this feeling. But the fact is that in most cases, mastectomy does not give you any better chance of long-term survival or a better outcome from treatment. Studies following thousands of women for more than 20 years show that when a lumpectomy can be done, mastectomy does not provide any better chance of survival than lumpectomy.

Although most women and their doctors prefer lumpectomy and radiation therapy when it’s a reasonable option, your choice will depend on a number of factors, such as:

* how you feel about losing your breast

* how you feel about getting radiation therapy

* how far you would have to travel and how much time it would take to have radiation therapy

* whether you think you will want to have more surgery to reconstruct your breast after having a mastectomy

* your preference for mastectomy as a way to ‘get rid of all your cancer as quickly as possible

* your fear of the cancer coming back

For some women, mastectomy may clearly be a better option. For example, lumpectomy or breast conservation therapy is usually not recommended for:

* women who have already had radiation therapy to the affected breast

* women with 2 or more areas of cancer in the same breast that are too far apart to be removed through 1 surgical incision, while keeping the appearance of the breast satisfactory

* women whose initial lumpectomy along with re-excision(s) has not completely removed the cancer

* women with certain serious connective tissue diseases such as scleroderma or lupus, which may make them especially sensitive to the side effects of radiation therapy

* pregnant women who would require radiation while still pregnant (risking harm to the fetus)

* women with a tumor larger than 5 cm (2 inches) across that doesn’t shrink very much with neoadjuvant chemotherapy

* women with inflammatory breast cancer

* women with a cancer that is large relative to her breast size

Other factors may need to be taken into account as well. For example, young women with breast cancer and a known BRCA mutation are at very high risk for a second cancer. These women may want to consider having a mastectomy, or even a double mastectomy, to both treat the cancer and reduce this risk.

Axillary lymph node dissection

To determine if the breast cancer has spread to axillary (underarm) lymph nodes, some of these lymph nodes may be removed and looked at under the microscope. This is an important part of staging and determining treatment and outcomes. When the lymph nodes are affected, there is an increased likelihood that cancer cells have spread through the bloodstream to other parts of the body.

As noted above, axillary lymph node dissection is part of a radical or modified radical mastectomy procedure. It may also be done along with a breast-conserving procedure, such as lumpectomy. Anywhere from about 10 to 40 (though usually less than 20) lymph nodes are removed.

The presence of cancer cells in the lymph nodes under the arm is an important factor in considering adjuvant therapy. Axillary dissection is used as a test to help guide other breast cancer treatment decisions.

Possible side effects: As with other operations, pain, swelling, bleeding, and infection are possible.

The main possible long-term effect of removing axillary lymph nodes is lymphedema (swelling of the arm). This occurs because any excess fluid in the arms normally travels back into the bloodstream through the lymphatic system. Removing the lymph nodes sometimes causes this fluid to remain and build up in the arm.

Up to 30% of women who have underarm lymph nodes removed develop lymphedema. It also occurs in up to 3% of women who have a sentinel lymph node biopsy (see below). It may be more common if radiation is given after surgery. Sometimes the swelling lasts for only a few weeks and then goes away. Other times, the swelling lasts a long time. Ways to help prevent or reduce the effects of lymphedema are discussed in the section, “What happens after treatment for breast cancer?” If your arm is swollen, tight, or painful after lymph node surgery, be sure to tell someone on your cancer care team right away.

You may also have short- or long-term limitations in moving your arm and shoulder after surgery. Your doctor may give you exercises to ensure that you do not have permanent problems with movement (a frozen shoulder). Numbness of the skin of the upper, inner arm is another common side effect because the nerve that controls sensation here travels through the lymph node area.

Sentinel lymph node biopsy

Although axillary lymph node dissection (ALND) is a safe operation and has low rates of side effects other than lymphedema, in many cases doctors will check the lymph nodes first with a sentinel lymph node biopsy (SLNB), which is a way of learning if cancer has spread to lymph nodes without removing all of them.

In this procedure the surgeon finds and removes the first lymph node(s) (sentinel node or nodes) to which a tumor drains, and the one(s) most likely to contain cancer cells if they have started to spread. To do this, the surgeon injects a radioactive substance and/or a blue dye into the tumor or the area around it. Lymphatic vessels will carry these substances into the sentinel node(s). The doctor can use a special device to detect the radioactivity in the nodes that the radioactive substance flows into or can look for lymph nodes that have turned blue. These are separate ways to find the sentinel node, but are often done together as a double check. The doctor then cuts the skin over the area and removes the nodes. These nodes (often 2 or 3) are then looked at closely by the pathologist. (Because fewer nodes are removed than in an ALND, each one can be looked at more closely for any cancer).

If there is no cancer in the sentinel node(s), it’s very unlikely that the cancer has spread to other lymph nodes, so no further lymph node surgery is needed. The patient can avoid the potential side effects of a full ALND (see above).

If the sentinel node(s) has cancer, the surgeon will do a full axillary lymph node dissection to see how many other lymph nodes are involved. The lymph node can sometimes be checked for cancer during surgery. If cancer is found in the sentinel lymph node, the surgeon may go on to remove more lymph nodes or even do a full axillary dissection. If no cancer cells are seen in the lymph node at the time of the surgery, or if the sentinel node is not checked at the time of the surgery, the lymph node(s) will be examined in greater detail over the next several days. If cancer is found in the lymph node, the surgeon may recommend a full axillary lymph node dissection at a later time.

Sentinel lymph node biopsy requires a great deal of skill. It should be done only by a surgical team known to have experience with this technique. If you are thinking about having this type of biopsy, ask your health care team if they do them regularly.

Reconstructive surgery

After having a mastectomy (or some breast-conserving surgeries), a woman may want to consider having the breast mound rebuilt; this is called breast reconstruction. These procedures are not done to treat cancer but to restore the breast’s appearance after surgery. If you are going to have breast surgery and are thinking about having reconstruction, it is important to consult with a plastic surgeon who is an expert in breast reconstruction before your surgery.

Decisions about the type of reconstruction and when it will be done depend on each woman’s medical situation and personal preferences. You may have a choice between having your breast reconstructed at the same time as the mastectomy (immediate reconstruction) or at a later time (delayed reconstruction). There are several types of reconstructive surgery. Some use saline (salt water) or silicone implants, while others use tissues from other parts of your body (autologous tissue reconstruction).

For a discussion of the different reconstruction options, see the American Cancer Society document, Breast Reconstruction After Mastectomy. You may also find it helpful to talk with a woman who has had the type of reconstruction you might be considering. Our Reach to Recovery volunteers can help you with this.

What to expect with surgery

For many, the thought of surgery can be frightening. But with a better understanding of what to expect before, during, and after the operation, many fears can be relieved.

Before surgery: The common biopsy procedures let you find out if you have breast cancer within a few days of your biopsy, but the extent of the breast cancer will not be known until after imaging tests and the surgery for local treatment are done.

Usually, you meet with your surgeon a few days before the operation to discuss the procedure. This is a good time to ask specific questions about the surgery and review potential risks. Be sure you understand what the extent of the surgery is likely to be and what you should expect afterward. If you are thinking about breast reconstruction, ask about this as well.

You will be asked to sign a consent form, giving the doctor permission to perform the surgery. Take your time and review the form carefully to be certain that you understand what you are signing. Sometimes, doctors send material for you to review in advance of your appointment, so you will have plenty of time to read it and won’t feel rushed. You may also be asked to give consent for researchers to use any tissue or blood that is not needed for diagnostic purposes. Although this may not be of direct use to you, it may be very helpful to women in the future.

You may be asked to donate blood before some operations, such as a mastectomy combined with natural tissue reconstruction, if the doctors think a transfusion might be needed. You might feel more secure knowing that if a transfusion is needed, you will receive your own blood. If you do not receive your own blood, it is important to know that in the United States, blood transfusion from another person is nearly as safe as receiving your own blood. Ask your doctor about your possible need for a blood transfusion.

Your doctor will review your medical records and ask you about any medicines you are taking. This is to be sure that you are not taking anything that might interfere with the surgery. For example, if you are taking aspirin, arthritis medicine, or a blood-thinning drug (like coumadin), you may be asked to stop taking the drug about a week or 2 before the surgery. Be sure you tell your doctor about everything you take, including vitamins and herbal supplements. Usually, you will be told not to eat or drink anything for 8 to 12 hours before the surgery, especially if you are going to have general anesthesia (will be asleep during surgery).

You will also meet with the anesthesiologist or nurse anesthetist, the health professional who will be giving you the anesthesia during your surgery. The type of anesthesia used depends largely on the kind of surgery being done and your medical history.

Surgery: Depending on the likely extent of your surgery, you may be offered the choice of an outpatient procedure (where you go home the same day) or you may be admitted to the hospital.

General anesthesia is usually given whenever the surgery involves a mastectomy or an axillary node dissection, and is most often used during breast-conserving surgery as well. You will have an IV (intravenous) line put in (usually in a vein in your arm), which the medical team will use to give medicines that may be needed during the surgery. Usually you will be hooked up to an electrocardiogram (EKG) machine and have a blood pressure cuff on your arm, so your heart rhythm and blood pressure can be checked during the surgery.

The length of the operation depends on the type of surgery being done. For example, a mastectomy with axillary lymph node dissection will usually take from 2 to 3 hours. After your surgery, you will be taken to the recovery room, where you will stay until you are awake and your condition and vital signs (blood pressure, pulse, and breathing) are stable.

After surgery: How long you stay in the hospital depends on the type of surgery being done, your overall state of health and whether you have any other medical problems, how well you do during the surgery, and how you feel after the surgery. Decisions about the length of your stay should be made by you and your doctor and not dictated by what your insurance will pay, but it is important to check your insurance coverage before surgery.

In general, women having a mastectomy and/or axillary lymph node dissection stay in the hospital for 1 or 2 nights and then go home. However, some women may be placed in a 23-hour, short-stay observation unit before going home.

Less involved operations such as lumpectomy and sentinel lymph node biopsy are usually done in an outpatient surgery center, and an overnight stay in the hospital is usually not needed.

You may have a dressing (bandage) over the surgery site that may wrap snugly around your chest. You may have one or more drains (plastic or rubber tubes) coming out from the breast or underarm area to remove blood and lymph fluid that collects during the healing process. Your health care team will teach you how to care for the drains, which may include emptying and measuring the fluid and identifying problems the doctor or nurse needs to know about. Most drains stay in place for 1 or 2 weeks. When drainage has decreased to about 30 cc (1 fluid ounce) each day, the drain will usually be removed.

Most doctors will want you to start moving your arm soon after surgery so that it won’t get stiff.

Many women who have a lumpectomy or mastectomy are often surprised by how little pain they have in the breast area. But they are less happy with the strange sensations (numbness, pinching/pulling feeling) they may feel in the underarm area.

Ask your health care team how to care for your surgery site and arm. Usually, they will give you and your caregivers written instructions about care after surgery. These instructions should include:

* the care of the surgical wound and dressing

* how to monitor drainage and take care of the drains

* how to recognize signs of infection

* when to call the doctor or nurse

* when to begin using the arm and how to do arm exercises to prevent stiffness

* when to resume wearing a bra

* when to begin using a prosthesis and what type to use (after mastectomy)

* what to eat and not to eat

* use of medications, including pain medicines and possibly antibiotics

* any restrictions of activity

* what to expect regarding sensations or numbness in the breast and arm

* what to expect regarding feelings about body image

* when to see your doctor for a follow-up appointment

* referral to a Reach to Recovery volunteer. Through our Reach to Recovery program, a specially trained volunteer who has had breast cancer can provide information, comfort, and support (see the American Cancer Society document, Reach to Recovery for more information).

Most patients see their doctor about 7 to 14 days after the surgery. Your doctor should explain the results of your pathology report and talk to you about the need for further treatment. If you will need more treatment, you may be referred to a radiation oncologist and/or a medical oncologist. If you are thinking about breast reconstruction, you may be referred to a plastic surgeon as well.

Post-mastectomy pain syndrome

Post-mastectomy pain syndrome (PMPS) is chronic nerve (neuropathic) pain after lumpectomy or mastectomy. Studies have shown that between 20% and 60% of women develop PMPS after surgery, but it is often not recognized as such. The classic signs of PMPS are chest wall pain and tingling down the arm. Pain may also be felt in the shoulder, scar, arm, or armpit. Other common complaints include numbness, shooting or pricking pain, or unbearable itching.

PMPS is thought to be linked to damage done to the nerves in the armpit and chest during surgery. But the causes are not known. Because major surgeries are less often used to treat breast cancer today, PMPS is becoming less of a problem.

It is important to talk to your doctor about any pain you are having. PMPS can cause you to not use your arm the way you should and over time you could lose the ability to use it normally.

PMPS can be treated. Opioids or narcotics are medicines commonly used to treat pain, but they may not work well for nerve pain. But there are medicines and treatments that do work for this kind of pain. Talk to your doctor to get the pain control you need.

Radiation Therapy

Radiation therapy is treatment with high-energy rays or particles that destroy cancer cells. This treatment may be used to kill any cancer cells that remain in the breast, chest wall, or underarm area after breast-conserving surgery. Radiation may also be needed after mastectomy in patients with either a cancer larger than 5 cm in size, or when cancer is found in the lymph nodes.

Radiation therapy can be given in 2 main ways.

External beam radiation

This is the most common type of radiation therapy for women with breast cancer. The radiation is focused from a machine outside the body on the area affected by the cancer.

The extent of radiation depends on whether a lumpectomy or mastectomy was done and whether or not lymph nodes are involved. If a lumpectomy was done, the entire breast gets radiation, and an extra boost of radiation is given to the area in the breast where the cancer was removed to prevent it from coming back in that area. Depending on the size and extent of the cancer, radiation may include the chest wall and underarm area as well. In some cases, the area treated may also include supraclavicular lymph nodes (nodes above the collarbone) and internal mammary lymph nodes (nodes beneath the breast bone in the center of the chest).

When given after surgery, external radiation therapy is usually not started until the tissues have been able to heal, often a month or longer. If chemotherapy is to be given as well, radiation therapy is usually delayed until chemotherapy is complete.

Before your treatments start, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. They will make some ink marks or small tattoos on your skin that they will use later as a guide to focus the radiation on the right area. You may want to talk to your health care team to find out if these marks will be permanent.

Lotions, powders, deodorants, and antiperspirants can interfere with external beam radiation therapy, so your health care team may tell you not to use them until treatments are complete.

External radiation therapy is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time — getting you into place for treatment — usually takes longer.

The most common way breast radiation is given is 5 days a week (Monday thru Friday) for about 6 weeks.

Accelerated breast irradiation: The standard approach of giving external radiation for 5 day a week over many weeks can be inconvenient for many women. Some doctors are now using other schedules, such as giving slightly larger daily doses over only 3 weeks, which seems to work about as well. Giving radiation in larger doses using fewer treatments is known as hypofractionated radiation therapy. Newer approaches now being studied give radiation over an even shorter period of time. In one approach, larger doses of radiation are given each day, but the course of radiation is shortened to only 5 days. In another approach, known as intraoperative radiation therapy (IORT), a single large dose of radiation is given in the operating room right after lumpectomy (before the breast incision is closed).

Other forms of accelerated radiation are described below in the section on brachytherapy. It is hoped that these newer approaches may prove to be at least equal to the current, standard breast irradiation, but few studies have been done comparing these new methods directly to standard radiation therapy. It is not known if the newer methods will still be as good as standard radiation after many years. For this reason, many doctors still consider them to be experimental at this time. Women who are interested in these approaches may want to ask their doctor about taking part in clinical trials of accelerated breast irradiation now going on.

3D-conformal radiotherapy: In this technique, the radiation is given with special machines so that it is aimed better at the area where the tumor was. This allows more of the healthy breast to be spared. Treatments are given twice a day for 5 days.

Possible side effects of external radiation: The main short-term side effects of external beam radiation therapy are swelling and heaviness in the breast, sunburn-like skin changes in the treated area, and fatigue. Your health care team may advise you to avoid exposing the treated skin to the sun because it may make the skin changes worse. Changes to the breast tissue and skin usually go away in 6 to 12 months.

In some women, the breast becomes smaller and firmer after radiation therapy. Having radiation may also affect a woman’s chances to have breast reconstruction. Radiation therapy of axillary lymph nodes also can cause lymphedema (see the section, “What will happen after treatment for breast cancer?”).

In rare cases, radiation therapy may weaken the ribs, which could lead to a fracture. In the past, parts of the lungs and heart were more likely to get some radiation, which could lead to long-term damage of these organs in some women. Modern radiation therapy equipment allows doctors to better focus the radiation beams, so these problems are rare today.

A very rare complication of radiation to the breast is the development of another cancer called angiosarcoma (see “What is breast cancer?”). These rare cancers can grow and spread quickly.

Brachytherapy

Brachytherapy, also known as internal radiation, is another way to deliver radiation therapy. Instead of aiming radiation beams from outside the body, radioactive seeds or pellets are placed directly into the breast tissue next to the cancer. It is often used as a way to add an extra boost of radiation to the tumor site (along with external radiation to the whole breast), although it may also be used by itself (see below). Tumor size, location, and other factors may limit who can get brachytherapy.

There are different types of brachytherapy.

Intracavitary brachytherapy: This method of brachytherapy consists of a small balloon attached to a thin tube. The deflated balloon is inserted into the space left by the lumpectomy and is filled with a salt water solution. (This can be done at the time of lumpectomy or within several weeks afterward.) The balloon and tube are left in place throughout treatment (with the end of the tube sticking out of the breast). Twice a day a source of radioactivity is placed into the middle of the balloon through the tube and then removed. This is done for 5 days as an outpatient treatment. The balloon is then deflated and removed. This system goes by the brand name, Mammosite®. This type of brachytherapy can also be considered a form of accelerated breast irradiation. Like other forms of accelerated breast irradiation, there are no studies comparing outcomes with this type of radiation directly with standard external beam radiation. It is not known if the long-term outcomes will be as good.

Interstitial brachytherapy: In this approach, several small, hollow tubes called catheters are inserted into the breast around the area of the lumpectomy and are left in place for several days. Radioactive pellets are inserted into the catheters for short periods of time each day and then removed. This method of brachytherapy has been around longer (and has more evidence to support it), but it is not used as much anymore.

While these methods are sometimes used as ways to add a boost of radiation to the tumor site (along with external radiation to the whole breast), they are also being studied in clinical trials as the only source of radiation for women who have had a lumpectomy. In this sense they can also be considered forms of accelerated partial breast irradiation. Early results have been promising, but long-term results are not yet available, and it’s not yet clear if irradiating only the area around the cancer will reduce the chances of the cancer coming back as much as giving radiation to the whole breast. The results of studies now being done will probably be needed before more doctors recommend accelerated partial breast irradiation as a standard treatment option.

Chemotherapy

Chemotherapy (chemo) is treatment with cancer-killing drugs that may be given intravenously (injected into a vein) or by mouth. The drugs travel through the bloodstream to reach cancer cells in most parts of the body. Chemo is given in cycles, with each period of treatment followed by a recovery period. Treatment usually lasts for several months.

When is chemotherapy used?

There are several situations in which chemotherapy may be recommended.

Adjuvant chemotherapy: Systemic therapy given to patients with no evidence of cancer after surgery is called adjuvant therapy. While surgery is used to remove all of the cancer that can be seen, adjuvant therapy is used to kill any cancer cells that may have been left behind that can’t be seen. Adjuvant therapy after breast-conserving surgery or mastectomy reduces the risk of breast cancer coming back. Both chemotherapy and hormone therapy can be used as adjuvant treatments.

Even in the early stages of the disease, cancer cells may break away from the primary breast tumor and spread through the bloodstream. These cells don’t cause symptoms, they don’t show up on imaging tests, and they can’t be felt during a physical exam. But if they are allowed to grow, they can establish new tumors in other places in the body. The goal of adjuvant chemotherapy is to kill undetected cells that have traveled from the breast.

Neoadjuvant chemotherapy: Chemotherapy given before surgery is called neoadjuvant therapy. Often, neoadjuvant therapy uses the same chemo that is used as adjuvant therapy (only it is given before surgery instead of after). In terms of survival, there is no difference between giving chemo before or after surgery. The major benefit of neoadjuvant chemotherapy is that it can shrink large cancers so that they are small enough to be removed by lumpectomy instead of mastectomy. Another possible advantage of neoadjuvant chemotherapy is that doctors can see how the cancer responds to chemotherapy. If the tumor does not shrink, your doctor may try different chemotherapy drugs.

Chemotherapy for advanced breast cancer: Chemotherapy can also be used as the main treatment for women whose cancer has already spread outside the breast and underarm area at the time it is diagnosed, or if it spreads after initial treatments. The length of treatment depends on whether the cancer shrinks, how much it shrinks, and how a woman tolerates treatment.

How is chemotherapy given?

In most cases (especially for adjuvant and neoadjuvant treatment), chemotherapy is most effective when combinations of more than one drug are used. Many combinations are being used, and it’s not clear that any single combination is clearly the best. Clinical studies continue to compare today’s most effective treatments against something that may be better.

Some of the most commonly used 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

* AC: doxorubicin (Adriamycin) and cyclophosphamide

* EC: epirubicin (Ellence) and cyclophosphamide

* TAC: docetaxel (Taxotere), doxorubicin (Adriamycin), and cyclophosphamide

* AC →  T: doxorubicin (Adriamycin) and cyclophosphamide followed by paclitaxel (Taxol) or docetaxel (Taxotere) (Herceptin may be given with the paclitaxel or docetaxel for HER2/neu positive tumors.)

* A →  CMF: doxorubicin (Adriamycin), followed by CMF

* CEF (FEC): cyclophosphamide, epirubicin, and 5-fluorouracil (this may be followed by docetaxel)

* TC: docetaxel (Taxotere) and cyclophosphamide

* TCH: docetaxel, carboplatin, and Herceptin for HER2/neu positive tumors

Other chemotherapy drugs used for treating women with breast cancer include cisplatin (Platinol), vinorelbine (Navelbine), capecitabine (Xeloda), pegylated liposomal doxorubicin (Doxil), gemcitibine (Gemzar), mitoxantrone, ixabepilone (Ixempra), and albumin-bound paclitaxel (Abraxane). The targeted therapy drugs Herceptin and Tykerb may be used with these chemo drugs for tumors that are HER2/neu-positive (these drugs are discussed in more detail in the “Targeted therapy” section).

Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period. The chemotherapy begins on the first day of each cycle, and then the body is given time to recover from the effects of chemotherapy. The chemotherapy drugs are then repeated to start the next cycle. The time between giving the chemotherapy drugs is generally 2 or 3 weeks and varies according the specific chemotherapy drug or combination of drugs. Some drugs are given more often. These cycles generally last for a total time of 3 to 6 months when given as adjuvant therapy, depending on the drugs used. Treatment may be longer for advanced breast cancer.

Dose-dense chemotherapy: Doctors have found that giving the cycles of chemo closer together can lower the chance that the cancer will come back and improve survival in some women. This usually means giving the same chemo that is normally given every 3 weeks (such as AC → T), but giving it every 2 weeks. In addition, a drug (growth factor) to help boost the white blood cell count is given after the chemo to make sure the white blood cell count returns to normal in time for the next cycle. This approach can lead to more side effects and be harder to take, so it is only used for adjuvant treatment in women with a higher chance of the cancer coming back after treatment. Recently, this approach was also used for neoadjuvant therapy. The patients getting treated more often had their tumors shrink more, were less likely to have the cancer come back, and lived longer than the patients treated every 3 weeks.

Possible side effects

Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects. Some women have many side effects while other women may have few.

The side effects of chemotherapy depend on the type of drugs, the amount taken, and the length of treatment. Some of the most common possible side effects 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)

* fatigue (due to low red blood cell counts and other reasons)

These side effects are usually short-term and go away after treatment is finished. It’s important to let your health care team know if you have any side effects, as there are often ways to lessen them. For example, drugs can be given to help prevent or reduce nausea and vomiting.

Several other side effects are also possible. Some of these are only seen with certain chemotherapy drugs. Your cancer care team will give you information about the possible side effects of the specific drugs you are getting.

Menstrual changes: For younger women, changes in menstrual periods are another possible side effect of chemotherapy. Premature menopause (not having any more menstrual periods) and infertility (not being able to become pregnant) are possible permanent complications of chemotherapy. Some chemotherapy drugs are more likely to do this than others. The older a woman is when she receives chemotherapy, the more likely it is that she will become infertile or menopausal as a result. When this happens, it can also lead to rapid bone loss from osteoporosis. Again, there are medicines that can help prevent this possible side effect.

You cannot depend on chemotherapy to prevent pregnancy, and getting pregnant while receiving chemotherapy could lead to birth defects and interfere with treatment. For this reason, it is important that pre-menopausal women who are sexually active discuss using birth control with their doctor. It is safe to have children after chemotherapy, but it’s not safe to get pregnant while on treatment. If you are pregnant when you get breast cancer, you still can be treated. Chemotherapy can be safely given during the last 2 trimesters of pregnancy.

Neuropathy: Several drugs used to treat breast cancer, including the taxanes (docetaxel and paclitaxel), platinum agents (carboplatin, cisplatin), and ixabepilone, can damage nerves outside of the brain and spinal cord. This can sometimes lead to symptoms (mainly in the hands and feet) such as numbness, pain, burning or tingling sensations, sensitivity to cold or heat, or weakness. In most cases this goes away once treatment is stopped, but it may be long-lasting in some women.

Heart damage: Adriamycin (doxorubicin), epirubicin, and some other drugs may cause permanent heart damage if used for a long time or in high doses. For this reason, doctors often check the patient’s heart function before starting one of these drugs. They also carefully control the doses and use echocardiograms or other heart tests to monitor heart function. If the heart function begins to decline, treatment with these drugs will be stopped. Still, in some patients, heart damage takes a long time to develop. They may show signs of poor heart function months or years later.

Chemobrain: Another possible side effect of chemotherapy is “chemobrain.” Many women who get chemotherapy for breast cancer report a slight decrease in mental functioning. There may be some problems with concentration and memory, which may last a long time. Still, most women do function well after chemotherapy. In studies that have found chemobrain to be a side effect of treatment, the symptoms most often go away within a few years. For more information, see the American Cancer Society document, Chemobrain.

Increased risk of leukemia: Very rarely, certain chemotherapy drugs may cause acute myeloid leukemia, a life-threatening cancer of white blood cells. When this happens it is usually within 10 years after treatment. In most women, chemotherapy’s benefits in preventing breast cancer from coming back or in extending life are likely to far exceed the risk of this serious but rare complication.

Feeling unwell or tired: Many women do not feel as healthy after receiving chemotherapy as they did before. There is often a residual feeling of body pain or achiness and a mild loss of physical functioning. These are very subtle changes that are only revealed by closely questioning women who have undergone chemotherapy.

Fatigue is another common (but often overlooked) problem for women who have received chemotherapy. This may last up to several years. It can often be helped, so it is important to let your doctor or nurse know about it. For more information on what you can do about fatigue, see the American Cancer Society document, Fatigue in People with Cancer. Exercise, naps, and conserving energy may be recommended. If there are sleep problems, these can be treated. Sometimes there is depression, which may be helped by counseling and/or medicines.

Hormone Therapy

Hormone therapy is another form of systemic therapy. It is most often used as an adjuvant therapy to help reduce the risk of cancer recurrence after surgery, although it can be used as neoadjuvant treatment, as well. It is also used to treat cancer that has come back after treatment or has spread.

A woman’s ovaries are the main source of the hormone estrogen up until menopause. After menopause, smaller amounts are still made in the body’s fat tissue, where a hormone made by the adrenal gland is converted into estrogen.

Estrogen promotes the growth of about 2 out of 3 of breast cancers — those containing estrogen receptors (ER-positive cancers) and/or progesterone receptors (PR-positive cancers). Because of this, several approaches to blocking the effect of estrogen or lowering estrogen levels are used to treat ER-positive and PR-positive breast cancers. Hormone therapy does not help patients whose tumors are both ER- and PR-negative.

Tamoxifen and toremifene (Fareston): These anti-estrogen drugs work by temporarily blocking estrogen receptors on breast cancer cells, preventing estrogen from binding to them. They are taken daily as a pill.

For women with ER- or PR-positive cancers, taking tamoxifen after surgery for 5 years reduces the chances of the cancer coming back by about half. Tamoxifen can also be used to treat metastatic breast cancer, as well as to reduce the risk of developing breast cancer in women at high risk. Toremifene works like tamoxifen, but is not used as often.

The most common side effects of these drugs include fatigue, hot flashes, vaginal dryness or discharge, and mood swings.

Some patients whose cancer has spread to their bones may experience a “tumor flare” with pain and swelling in the muscles and bones. This usually subsides quickly, but in some cases the patient may also develop a high calcium level in the blood that cannot be controlled. If this occurs, the treatment may need to be stopped.

Rare, but more serious side effects are also possible. These drugs can increase the risk of developing cancers of the uterus (endometrial cancer and uterine sarcoma). Tell your doctor right away about any unusual vaginal bleeding (a common symptom of both of these cancers). Most uterine bleeding is not from cancer, but this symptom always needs prompt attention.

Another possible serious side effect is blood clots, which usually form in the legs. In some cases, these may lead to a heart attack, stroke, or blockage in the lungs (pulmonary embolism). Call your doctor or nurse right away if you develop pain, redness, or swelling in your lower leg (calf), shortness of breath, chest pain, sudden severe headache, confusion, or trouble speaking or moving.

Depending on a woman’s menopausal status, tamoxifen can have different effects on the bones. In pre-menopausal women tamoxifen can cause some bone thinning, but in post-menopausal women it is often good for bone strength. The effects of toremifene on the bones are less clear.

For most women with breast cancer, the benefits of taking these drugs outweigh the risks.

Fulvestrant (Faslodex®): Fulvestrant is a drug that also acts on the estrogen receptor, but instead of blocking it, this drug eliminates it. It is often effective even if the breast cancer is no longer responding to tamoxifen. It is given by injection once a month. Hot flashes, mild nausea, and fatigue are the major side effects. It is currently only approved for use in post-menopausal women with advanced breast cancer that no longer responds to tamoxifen or toremifene.

Aromatase inhibitors: Three drugs that stop estrogen production in post-menopausal women have been approved to treat both early and advanced breast cancer: letrozole (Femara®), anastrozole (Arimidex®), and exemestane (Aromasin®). They work by blocking an enzyme (aromatase) responsible for making small amounts of estrogen in post-menopausal women. They cannot stop the ovaries of pre-menopausal women from making estrogen, so they are only effective in post-menopausal women. These drugs are taken daily as pills.

Several studies have compared these drugs with tamoxifen as adjuvant hormone therapy in post-menopausal women. Using these drugs, either alone or after tamoxifen, has been shown to better reduce the risk of cancer recurrence than using tamoxifen alone for 5 years.

For post-menopausal women whose cancers are estrogen and/or progesterone receptor–positive, most doctors now recommend using an aromatase inhibitor at some point during adjuvant therapy. But several important questions have not yet been answered. It’s not yet clear if starting adjuvant therapy with one of these drugs is better than giving tamoxifen and then switching to an aromatase inhibitor. If tamoxifen is given first, it’s not clear how long it should be given. The optimal length of treatment with aromatase inhibitors has not yet been determined, nor has it been shown if any one of these drugs is better than the others. Studies now being done should help answer these questions.

The aromatase inhibitors tend to have fewer serious side effects than tamoxifen — they don’t cause uterine cancers and very rarely cause blood clots. They can, however, cause muscle pain and joint stiffness and/or pain. The joint pain may be similar to a new feeling of having arthritis in many different joints at one time. Because aromatase inhibitors remove all estrogens from women after menopause, they also cause bone thinning, sometimes leading to osteoporosis and even fractures. Many women treated with an aromatase inhibitor are also treated with medicine to strengthen their bones, such as bisphosphonates.

Ovarian ablation: In pre-menopausal women, removing or shutting down the ovaries, which are the main source of estrogens, effectively makes the woman post-menopausal. This may allow some other hormone therapies to work better.

Permanent ovarian ablation can be done by surgically removing the ovaries. This operation is called an oophorectomy. More often, ovarian ablation is done with drugs called luteinizing hormone-releasing hormone (LHRH) analogs, such as goserelin (Zoladex®) or leuprolide (Lupron®). These drugs stop the signal that the body sends to ovaries to make estrogens. They can be used alone or with tamoxifen as hormone therapy in pre-menopausal women. They are also being studied as adjuvant therapies along with aromatase inhibitors in pre-menopausal women.

Chemotherapy drugs may also damage the ovaries of pre-menopausal women so they no longer produce estrogen. In some women ovarian function returns months or years later, but in others, the damage to the ovaries is permanent and leads to menopause. This can sometimes be a helpful (if unintended) consequence of chemotherapy with regard to breast cancer treatment, although it leaves the woman infertile.

All of these methods can cause a woman to have symptoms of menopause, including hot flashes, night sweats, vaginal dryness, and mood swings.

Megestrol acetate: Megestrol acetate (Megace®) is a progesterone-like drug used as a hormone treatment of advanced breast cancer, usually for women whose cancers do not respond to the other hormone treatments. Its major side effect is weight gain, and it is sometimes used in higher doses to reverse weight loss in patients with advanced cancer. This is an older drug that is no longer used very often.

Other ways to control hormones: Androgens (male hormones) may be considered after other hormone treatments for advanced breast cancer have been tried. They are sometimes effective, but they can cause masculine characteristics such as an increase in body hair and a deeper voice to develop.

Targeted Therapy

As researchers have learned more about the gene changes in cells that cause cancer, they have been able to develop newer drugs that specifically target these changes. These targeted drugs work differently from standard chemotherapy drugs. They often have different (and less severe) side effects. They are most often used along with chemotherapy at this time.

Drugs that target the HER2/neu protein

Trastuzumab (Herceptin): Trastuzumab is a type of drug known as a monoclonal antibody — a man-made version of a very specific immune system protein. It attaches to a growth-promoting protein known as HER2/neu (or just HER2), which is present in larger than normal amounts on the surface of the breast cancer cells in about 1 of 5 patients. Breast cancers with too much of this protein tend to grow and spread more aggressively. Trastuzumab can help slow this growth and may also stimulate the immune system to more effectively attack the cancer.

Trastuzumab is given as an injection into a vein (IV), usually once a week or as a larger dose every 3 weeks. The optimal length of time to give it is not yet known.

Trastuzumab is often used (along with chemotherapy) as adjuvant therapy for HER2-positive cancers to reduce the risk of recurrence when the tumor is larger than 1 cm across or when the cancer has spread to the lymph nodes. It is given along with chemotherapy for 3 to 6 months, and then given on its own, usually for a total of a year of treatment. Studies looking at how long this drug needs to be given are going on now

Trastuzumab can also shrink some HER2-positive advanced breast cancers that return after chemotherapy or continue to grow during chemotherapy. Treatment that combines trastuzumab with chemotherapy may work better than chemotherapy alone in some patients.

Compared with chemotherapy drugs, the side effects of trastuzumab are relatively mild. They may include fever and chills, weakness, nausea, vomiting, cough, diarrhea, and headache. These side effects occur less often after the first dose.

A more serious potential side effect is heart damage leading to a problem called congestive heart failure. For most (but not all) women, this effect has been temporary and has improved when the drug is stopped. The risk of heart problems is higher when trastuzumab is given with certain chemotherapy drugs such as doxorubicin (Adriamycin) and epirubicin (Ellence). Major symptoms of congestive heart failure are shortness of breath, leg swelling, and severe fatigue. Women having these symptoms should call their doctor right away.

Lapatinib (Tykerb): Lapatinib is another drug that targets the HER2 protein. This drug is given as a pill to women with advanced HER2-positive breast cancer that is no longer helped by chemotherapy and trastuzumab. It is also being studied as an adjuvant therapy in HER2-positive patients, but at this time is only used for advanced breast cancer. In advanced breast cancer it is often given along with the chemotherapy drug capecitabine (Xeloda).

The most common side effects of this drug include diarrhea, nausea, vomiting, rash, and something called hand-foot syndrome. Symptoms of hand-foot syndrome may include numbness, tingling, redness, swelling, and discomfort in the hands and feet. Sometimes peeling of the skin also occurs. Diarrhea is a common side effect and can be severe, so it is very important to let your health care team know about any changes in bowel habits as soon as they happen.

In rare cases lapatinib may cause liver problems or a decrease in heart function (that can lead to shortness of breath), although this seems to go away once treatment is finished.

Drugs that target new tumor blood vessels (angiogenesis)

Tumors need to develop and maintain new blood vessels in order to grow. Drugs that target these blood vessels are proving to be helpful against a variety of cancers, including breast cancer.

Bevacizumab (Avastin®) is a monoclonal antibody that may be used in patients with metastatic breast cancer. This antibody is directed against vascular endothelial growth factor, a protein that helps tumors form new blood vessels.

Bevacizumab is given by intravenous (IV) infusion. It is most often used in combination with the chemotherapy drug paclitaxel (Taxol).

Rare, but possibly serious side effects include bleeding, holes forming in the colon (requiring surgery to correct), and slow wound healing.

More common side effects include high blood pressure, tiredness, blood clots, low white blood cell counts, headaches, mouth sores, loss of appetite, and diarrhea. High blood pressure is very common, so it very important that your doctor watches your blood pressure carefully during treatment.

Treatment of stage 0 (non-invasive) breast cancer

The 2 types of non-invasive breast cancers, lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS), are treated very differently.

LCIS: Since this is not a true cancer, no immediate or active treatment is recommended for most women with LCIS. But because having LCIS increases your risk of developing invasive cancer later on, close follow-up is very important. This usually includes a yearly mammogram and a clinical breast exam. Women with LCIS may also want to talk with their doctors about the benefits and limits of being screened yearly with magnetic resonance imaging (MRI) in addition to mammograms. Close follow-up of both breasts is important because women with LCIS in one breast have an equal risk of developing breast cancer on the same or opposite side.

Women with LCIS may also want to consider taking tamoxifen or raloxifene to reduce their risk of breast cancer or taking part in a clinical trial for breast cancer prevention. For more information on drugs to reduce breast cancer risk see the American Cancer Society document, Medicines to Reduce Breast Cancer Risk. They may also wish to discuss other possible prevention strategies (such as reaching an optimal body weight or starting an exercise program) with their doctor.

Some women with LCIS may choose to have a bilateral simple mastectomy (removal of both breasts but not axillary lymph nodes) to try to reduce their risk of breast cancer, especially if they have other risk factors, such as a strong family history. Depending on the woman’s preference, she may consider immediate or delayed breast reconstruction.

DCIS: In most cases, a woman with DCIS can choose between breast-conserving therapy (lumpectomy, usually followed by radiation therapy) and simple mastectomy. Lymph node removal (axillary dissection) is usually not needed. Lumpectomy without radiation therapy is only an option for certain women who had small areas of low-grade DCIS that was removed with large enough cancer-free surgical margins. Most women who have a lumpectomy, however, will require radiation therapy.

Mastectomy may be necessary if the area of DCIS is very large, if the breast has several areas of DCIS, or if lumpectomy cannot completely remove the DCIS (that is, the lumpectomy specimen and re-excision specimens have cancer cells in the surgical margins). Women having a mastectomy for DCIS may have reconstruction immediately or later.

If the DCIS is estrogen receptor-positive, treatment with tamoxifen for 5 years after surgery can lower the risk of another DCIS or invasive cancer developing in either breast. Women may want to discuss the pros and cons of this option with their doctors.

Treatment of Breast Cancer During Pregnancy

Breast cancer is diagnosed in about 1 pregnant woman out of 3,000. In general, treatment recommendations depend upon how long the woman has been pregnant.

Radiation therapy during pregnancy is known to increase the risk of birth defects, so it is not recommended for pregnant women with breast cancer. For this reason, breast-conserving therapy (lumpectomy and radiation therapy) is only an option if treatment can wait until it is safe to deliver the baby. However, breast biopsy procedures and even modified radical mastectomy are safe for the mother and fetus.

For a long time it was assumed that chemotherapy was dangerous to the fetus. However, several recent studies have found that using certain chemotherapy drugs during the second and third trimesters (the fourth to ninth months) does not increase the risk of birth defects. Because of concern about the potential damage to the fetus, the safety of chemotherapy during the first trimester (the first 3 months) of pregnancy has not been studied.

Hormone therapy may affect the fetus and should not be started until after the patient has given birth.

Many chemotherapy and hormone therapy drugs can enter breast milk and could be passed on to the baby, so breast-feeding is not usually recommended during chemotherapy or hormone therapy.

Treatment of Invasive Breast Cancer by Stage

Breast-conserving surgery is often appropriate for earlier-stage invasive breast cancers if the cancer is small enough, although mastectomy is also an option. If the cancer is too large, a mastectomy will be needed, unless pre-operative (neoadjuvant) chemotherapy can shrink the tumor enough to allow breast-conserving surgery. In either case, the lymph nodes will need to be checked and removed if they contain cancer. Radiation will be needed for almost all patients who have breast-conserving surgery and some who have mastectomy. Adjuvant systemic therapy after surgery is typically recommended for all cancers larger than 1 cm (about 1/2 inch) across and for some that are smaller.

Stage I

These cancers are still relatively small and have not spread to the lymph nodes or elsewhere.

Local therapy: Stage I cancers can be treated with either breast-conserving surgery (lumpectomy, partial mastectomy) or modified radical mastectomy. The lymph nodes will also need to be evaluated, with a sentinel lymph node biopsy or an axillary lymph node dissection. Breast reconstruction can be done either at the same time as surgery or later.

Radiation therapy is usually given after breast-conserving surgery. Women who may consider breast-conserving surgery without radiation therapy typically have all of the following:

* they are age 70 years or older

* they have a tumor 2 cm or less across that has been completely removed

* they have a tumor that contains hormone receptors and hormone therapy is given

* none of the lymph nodes that were removed contained cancer

Although some women who do not meet these criteria may be tempted to avoid radiation, studies have shown that not getting radiation increases the chances of the cancer coming back.

Adjuvant systemic therapy: Most doctors will discuss the pros and cons of adjuvant hormone therapy (either tamoxifen or an aromatase inhibitor) with all women who have a hormone receptor–positive (estrogen or progesterone) breast cancer, no matter how small the tumor. Women with tumors larger than 0.5 cm (about 1/4 inch) across may be more likely to benefit from it.

If the tumor is smaller than 1 cm (about 1/2 inch) across, adjuvant chemotherapy is not usually offered. Some doctors may suggest it if a cancer smaller than 1 cm has any unfavorable features (such as being high-grade, estrogen receptor–negative, HER2-positive, or having a high score on one of the gene panels). Adjuvant chemotherapy is usually recommended for larger tumors.

For HER2-positive cancers larger than 1 cm across, adjuvant trastuzumab (Herceptin) is usually recommended as well.

See below for more information on adjuvant therapy.

Stage II

These cancers are larger and/or have spread to a few nearby lymph nodes.

Local therapy: Surgery and radiation therapy options for stage II tumors are similar to those for stage I tumors, except that in stage II, radiation therapy may be considered even after mastectomy if the tumor is large (more than 5 cm across) or the cancer is found after surgery to have spread to several lymph nodes.

Adjuvant systemic therapy: Adjuvant systemic therapy is recommended for women with stage II breast cancer. It may involve hormone therapy, chemotherapy, trastuzumab, or some combination of these, depending on the patient’s age, estrogen-receptor status, and HER2/neu status. See the following section for more information on adjuvant therapy.

Neoadjuvant therapy: An option for some women who would like to have breast-conserving therapy for tumors larger than 2 cm (about 4/5 inch across) is to have neoadjuvant (before surgery) chemotherapy, hormone therapy, and/or trastuzumab to shrink the tumor.

If the neoadjuvant treatment shrinks the tumor enough, women may then be able to have breast-conserving surgery (such as lumpectomy) followed by radiation therapy, as well as hormone therapy if the tumor is hormone receptor-positive. Further chemotherapy may also be considered. If the tumor does not shrink enough for breast-conserving surgery, then mastectomy may be required. This may be followed by different chemotherapy. Radiation therapy may be needed if the tumor is large (more than 2 inches across) or if lymph nodes contain cancer. Radiation is usually given after surgery Also, hormone therapy may be given if the tumor is estrogen receptor–positive. Hormone therapy can be given both before and after surgery. A woman’s chance for survival from breast cancer does not seem to be affected by whether she gets her chemotherapy before or after her breast surgery.

Stage III

Local treatment for some stage IIIA breast cancers is largely the same as that for stage II breast cancers. They may be removed by breast-conserving surgery (such as lumpectomy) followed by radiation therapy, or by modified radical mastectomy (with or without breast reconstruction). Sentinel lymph node biopsy or axillary lymph node dissection is also done. Radiation therapy may be used after mastectomy if the tumor is large (more than 5 cm across) or is found to have spread to several lymph nodes. Neoadjuvant therapy may be an option for some women who would like to have breast-conserving therapy.

Surgery is usually followed by adjuvant systemic chemotherapy, and/or hormone therapy, and/or trastuzumab. (See the following section for more information on adjuvant therapy.)

More advanced stage IIIA, as well as stage IIIB and IIIC cancers, are often treated with chemotherapy before surgery. Then a modified radical mastectomy is done, with or without reconstruction. Breast-conserving surgery may be an option for some women. The nearby lymph nodes will be sampled. Surgery is followed by radiation therapy, even if a mastectomy is done. Adjuvant chemotherapy may also be given, and adjuvant hormone therapy is offered to all women with hormone receptor–positive breast cancers.

Adjuvant therapy for stages I to III breast cancer

Adjuvant drug therapy may be recommended, based on the tumor’s size, spread to lymph nodes, and other prognostic features. If it is, you may get chemotherapy, trastuzumab (Herceptin), hormone therapy, or some combination of these.

Hormone therapy: Hormone therapy is not likely to be effective for women with hormone receptor-negative tumors. Hormone therapy is frequently offered to all women with hormone receptor–positive invasive breast cancer regardless of the size of the tumor or the number of lymph nodes involved.

Women who are still having periods and have hormone receptor–positive tumors can be treated with tamoxifen, which blocks the effects of estrogen being made by the ovaries. Some doctors also give a luteinizing hormone-releasing hormone (LHRH) analog, which makes the ovaries temporarily stop functioning. Another (permanent) option is surgical removal of the ovaries (oophorectomy). If the woman becomes post-menopausal within 5 years of starting tamoxifen (either naturally or because her ovaries are removed), she may be switched from tamoxifen to an aromatase inhibitor.

Sometimes a woman will stop having periods after chemotherapy or while on tamoxifen. But this does not necessarily mean she is truly post-menopausal. The woman’s doctor can do blood tests for certain hormones to determine her menopausal status. This is important because the aromatase inhibitors will only benefit post-menopausal women.

Women no longer having periods, or who are known to be in menopause at any age, and who have hormone receptor–positive tumors will generally get adjuvant hormone therapy either with an aromatase inhibitor (typically for 5 years), or with tamoxifen for several years followed by an aromatase inhibitor. For women who can’t take aromatase inhibitors, an alternative is tamoxifen for 5 years.

As mentioned before, there are still many unanswered questions about the best way to use these drugs. For example, it’s not clear if starting adjuvant therapy with one of these drugs is better than giving tamoxifen for some length of time and then switching to an aromatase inhibitor. Nor has the optimal length of treatment with aromatase inhibitors been determined. Studies now under way should help answer these questions. You might want to discuss these newer treatments with your doctor.

If chemotherapy is to be given as well as a general rule, hormone therapy is started after chemotherapy is completed.

Chemotherapy: Chemotherapy is usually recommended for all women with an invasive breast cancer whose tumor is hormone receptor-negative, and for women with hormone receptor-positive–tumors who may get additional benefit from having chemotherapy along with their hormone therapy, based on the stage and characteristics of their tumor.

Adjuvant chemotherapy can decrease the risk of the cancer coming back, but it does not remove the risk completely. Before deciding if it’s right for you, it is important to understand the chance of your cancer returning and how much adjuvant therapy will decrease that risk.

The specific drug regimens and the length of treatment are often determined by the stage and grade of the cancer. The typical chemotherapy regimens are listed in the chemotherapy section. The length of these regimens usually ranges from 4 to 6 months. In some cases, dose dense chemotherapy may be used.

Trastuzumab (Herceptin): Women who have HER2-positive cancers are usually given trastuzumab along with chemotherapy as part of their treatment.

A common chemotherapy regimen is doxorubicin (Adriamycin) and cyclophosphamide together for about 3 months, followed by paclitaxel (Taxol) and trastuzumab. The paclitaxel is given for about 3 months, while the trastuzumab is given for about 1 year.

A concern among doctors is that giving the trastuzumab so soon after doxorubicin may lead to heart problems, so heart function is watched closely during treatment with tests such as echocardiograms.

To try to lessen the possible effects on the heart, doctors are also looking for effective chemotherapy combinations that don’t contain doxorubicin. One such regimen is called TCH. It uses the chemotherapy drugs docetaxel (Taxotere) and carboplatin given every 3 weeks along with weekly trastuzumab (Herceptin) for 6 cycles. This is followed by trastuzumab every 3 weeks for a year.

Aids for adjuvant therapy decision making: Some doctors may use newer gene pattern tests to help decide whether to give adjuvant chemotherapy to women with certain stage I or II breast cancers. Examples of such tests include Oncotype DX® and MammaPrint®, which are described in more detail in the section “How is breast cancer diagnosed?” These tests are done on a sample of your breast cancer tissue. They look at the function of several genes within the cancer to help predict the risk of it returning after treatment. The tests will not tell your doctor which is the best hormone therapy or chemotherapy to recommend. Clinical trials are now being done to see if these tests can really tell which women can do without adjuvant chemotherapy in situations where doctors are often uncertain, such as in women with small tumors and uninvolved lymph nodes.

For help in deciding if adjuvant therapy is right for you, you might want to visit the Mayo Clinic Web site at www.mayoclinic.com and type “adjuvant therapy for breast cancer” into the search box. You will find a page that will help you to understand the possible benefits and limits of adjuvant therapy.

Other online guides, such as www.adjuvantonline.com, are designed to be used by health care professionals. This Web site provides information about your risk of the cancer returning within the next 10 years and what benefits you might expect from hormone therapy and/or chemotherapy. You may want to ask your doctor if he or she uses this site.

Stage IV

Stage IV cancers have spread beyond the breast and lymph nodes to other parts of the body. Although surgery and/or radiation may be useful in some situations (see below), they are very unlikely to cure these cancers, so systemic therapy is the main treatment. Depending on many factors, this may consist of hormone therapy, chemotherapy, targeted therapies such as trastuzumab (Herceptin) or bevacizumab (Avastin), or some combination of these treatments.

Trastuzumab may help women with HER2-positive cancers live longer if it is given with the first chemotherapy for stage IV disease. It is not yet known whether it also should be given at the same time as hormone therapy, or how long a woman should remain on therapy.

Bevacizumab, a drug that blocks new tumor blood vessel growth, has been shown to slow the progression of advanced breast cancer when it is combined with the chemotherapy drug paclitaxel (Taxol). See the section “Targeted therapy” for more information on this drug.

All of the systemic therapies given for breast cancer — hormone therapy, chemotherapy, and the newer targeted therapies — have potential side effects, which were described in previous sections. Your doctor will explain to you the benefits and risks of these treatments before prescribing them.

Radiation therapy and/or surgery may also be used in certain situations, such as to treat a small number of metastases in a certain area, to prevent bone fractures or blockage in the liver, or to provide relief of pain or other symptoms. If your doctor recommends such local treatments, it is important that you understand their goal — whether it is to try to cure the cancer or to prevent or treat symptoms.

In some cases, regional chemotherapy (where drugs are delivered directly into a certain area, such as the fluid around the brain) may be useful as well.

Treatment to relieve symptoms depends on where the cancer has spread. For example, pain from bone metastases may be treated with external beam radiation therapy and/or bisphosphonates such as pamidronate (Aredia) or zoledronic acid (Zometa). Most doctors recommend bisphosphonates (along with calcium and vitamin D) for all patients whose breast cancer has spread to their bones. (For more information about treatment of bone metastases, see the American Cancer Society document, Bone Metastasis.)

Advanced cancer that progresses during treatment: Although treatment for advanced breast cancer can often shrink or slow the growth of the cancer (often for many years), it may stop working after a time. Further treatment at this point depends on several factors, including previous treatments, where the cancer is located, and a woman’s age, general health, and desire to continue getting treatment.

For hormone receptor–positive cancers that were being treated with hormone therapy, switching to another type of hormone therapy is sometimes helpful. If not, chemotherapy is usually the next step.

For cancers that are no longer responding to one chemotherapy regimen, trying another may be helpful. There are many different drugs and combinations that can be used to treat breast cancer. However, each time a cancer progresses during treatment it becomes less likely that further treatment will have an effect.

HER2-positive cancers that no longer respond to trastuzumab may respond to lapatinib (Tykerb), another drug that attacks the HER2 protein. This drug is usually given along with the chemotherapy drug capecitabine (Xeloda). Both of these drugs are taken as pills.

Because current treatments are very unlikely to cure advanced breast cancer, patients in otherwise good health are encouraged to think about taking part in clinical trials of other promising treatments.

Recurrent breast cancer

Cancer is called recurrent when it come backs after treatment. Recurrence can be local (in the same breast or near the mastectomy scar) or in a distant area. Cancer that is found in the opposite breast is not a recurrence — it is a new cancer that requires its own treatment.

Local recurrence: Treatment of women whose breast cancer has recurred locally depends on their initial treatment. If the woman had breast-conserving therapy, local recurrence in the breast is usually treated with mastectomy. If the initial treatment was mastectomy, recurrence near the mastectomy site is treated by removing the tumor whenever possible. This is followed by radiation therapy, but only if none had been given after the original surgery. (Radiation can’t be given to the same area twice.) In either case, hormone therapy, trastuzumab, chemotherapy, or some combination of these may be used after surgery and/or radiation therapy.

Distant recurrence: In general, women who have a recurrence involving organs such as the bones, lungs, brain, etc., are treated the same way as those found to have stage IV breast cancer in these organs when they were first diagnosed (see treatment for stage IV). The only difference is that treatment may be affected by previous treatments a woman has had.

Should your cancer come back, the American Cancer Society document, When Your Cancer Comes Back: Cancer Recurrence can provide you with more general information on how to manage and cope with this phase of your treatment.