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Chemotherapy

Chemotherapy is a systemic therapy used to treat breast cancer. Systemic therapies circulate the drug, or combination of drugs, throughout your body. Many women have undetectable microscopic cells in other parts of their bodies at the time of diagnosis. Adjuvant systemic therapy, or therapy given to you after your initial cancer treatment, is an attempt to treat these cells either by killing them or changing the environment in which they exist or both.

How Chemotherapy Works

Cells go through several steps in the process of cell division, or reproduction. Chemotherapy drugs interfere with this process so that the cells can’t divide and consequently die. Different drugs are used in this process at different points, and often more than one kind of drug is used at a time. Unfortunately this effect on cell division acts on all cells that are rapidly dividing—not just cancer cells but also hair cells and bone marrow cells. Bone marrow continuously produces red blood cells, white blood cells, and platelets. This is one of the reasons chemotherapy is given in cycles, with a time lapse between treatments to allow the bone marrow to recover.

Another reason the drugs are given in cycles is that not all the cancer cells are dividing at any one time. The first treatment kills one group of cells; three weeks later a new set of cancer cells is starting to divide, and the drugs knock them out too. The idea is to decrease the total cancer cells to a number small enough for your immune system to take care of, without wiping out the immune system.

Systemic therapies are used because breast cancer deaths are rarely caused by a tumor in the breast. Rather, they are caused by breast cancer cells that get out of the breast and spread to other parts of the body such as the lungs, liver, bone, or brain. Systemic therapy does not guarantee that your cancer will be cured, it may simply prolong the time to recurrence. But that in itself can be a worthwhile goal. The key, however, is to actually understand what the treatments are providing and whether they are worth it.

Chemotherapy is often given after surgery, but not always. It sometimes make sense to have chemotherapy (or hormonal therapy) first to shrink the primary tumor and and see how your cancer will respond to the drugs you are taking.

Initially, adjuvant therapies were given to all women whose cancer had spread to their lymph nodes. As newer drugs have been developed they have been added to the mix, and often given to women with negative nodes as well. As we have figured out the different types of breast cancer we have become better able to match the treatments to the patients, both in terms of their risk of recurrence and the potential benefit of the therapy.

You should talk to your doctor about how much benefit you are getting from chemotherapy. This is determined by the type of cancer you have and your risk for recurrence. In general, chemotherapy reduces the risk of recurrence by about a third. This means the higher the chance of recurrence, the more beneficial the chemotherapy is likely to be for you. If you have a 60% chance of recurrence, a one-third risk reduction means chemo will reduce that chance by 20%, but if you have a nine percent chance of recurrence the one-third reduction is only three percent, although the effects are not perfectly linear.

You should also have your doctor tell you the absolute benefit of chemotherapy. For example, if your chances of dying within 10 years were 50% and you had a treatment that reduced the risk of mortality by 50%, your absolute benefit at 10 years would be 25%. Another way to think about that statistic is this: If there are 100 women with the same cancer as you, then 50 of them would die within 10 years. If a treatment reduces the chance of dying by 50% then 25 of them would die within 10 years. (Keep in mind, though, that during those 10 years there are other things that can kill us, from car accidents to pneumonia.)

You can get accurate survival or recurrence statistics for your own case in a several ways. There are two online tools available to oncologists, Adjuvant! and Numeracy, that can make precise calculations for you. Ask your oncologist to provide you with the data from the Adjuvant! or Numeracy. You can use these online tools yourself, too. Make sure your oncologist also discusses the short- and long-term side effects of the therapy being proposed so you won’t be surprised later.

There are general guidelines for breast cancer treatment, drawn up by a group of nationwide breast cancer specialists, such as the National Comprehensive Cancer Network and American Society of Clinical Oncology.

Types of Chemotherapy

The effectiveness of chemotherapy depends on which drug or drug combination you use. Currently, the best results come from the use of sequential combination chemotherapy containing anthracyclines, alkylating agents, and taxanes. There are two large clinical trials now underway that choose adjuvant therapy based on genetic signature of the tumor.The TAILORx trial is investigating whether this approach is effective for women with node-negative tumors. The RxPONDER trial is investigating whether the approach is effective for women with node positive tumors. Findings from these trials are expected to help oncologists determine the best chemotherapy options, based on tumor type.

Since there are choices to be made among different chemotherapy drugs, it’s especially important for the patient to participate in the decision-making process. Don’t be afraid to ask why your doctor has chosen a particular treatment regimen and ask to see studies that back it up. Find out exactly what the differences are in efficacy and side effects. Some drugs, like doxorubicin (Adriamycin), for example, can be more toxic to the heart. Also, some drugs are more likely to put you into menopause and render you infertile than others. If you are premenopausal and still want to have children some day, you need to tell your doctors so they can take that into consideration. Before starting treatment, you should also meet with a fertility counselor to discuss your options for egg or embryo freezing. (LiveStrong/Fertile Hope is a good place to get started.)

Seven drugs are commonly given as adjuvant chemotherapy for breast cancer:

  • cyclophosphamide (Cytoxan) (C)
  • methotrexate (M)
  • 5-fluorouracil (F)
  • doxorubicin (Adriamycin) (A)
  • epirubicin (E)
  • paclitaxel (Taxol)
  • docetaxel (Taxotere) (T)

These are usually given in combinations, CMF or AC followed by T or FEC or TAC. In addition, drugs are given to maintain your white blood count. These are typically filgrastim (Neupogen) and sargramostim (Leukine), which are taken as injections daily over 10 to 14 days. Another option is  pegfilgrastim (Neulasta), which is only injected once during a chemotherapy cycle.

Other drugs are used for metastatic disease. Some of the most common are:

  • abraxane
  • gemzar
  • xeloda

While you are on chemotherapy your immune system will not be functioning at its best. Although your blood cells may be fairly normal, the immune system is affected in less obvious ways. This doesn’t mean you have to hide in your house and avoid all contact with other people  during therapy. Talk with your oncologist or nurse about your daily activities. You should make sure you are up to date with your vaccinations before you start your chemotherapy. You may also want to get a good dental cleaning if there is time (you do not want to do this during chemotherapy, as dental cleanings can introduce bacteria into your bloodstream while your counts are low). Practice good hand-washing and consider carrying a small bottle of alcohol-based sanitizer for when you can’t get to a sink. Wear a mask if you are around people with colds or flu.

Timing of Chemotherapy

Classically, chemotherapy treatment follows surgery. But another course is neoadjuvant (or pre­operative) chemotherapy, when the chemotherapy is given prior to surgery. Giving chemotherapy before surgery doesn’t improve survival, but it does allow your oncologist to see whether or not the chemo works. If the tumor starts melting away, we know the chemotherapy is working. If not, it means a different chemotherapy regimen should be used after surgery. Most surgeons will consider preoperative chemotherapy along with a HER2-targeted therapy, if indicated, for women who have a tumor over three centimeters in size and who would like to have a lumpectomy instead of a mastectomy or have positive lymph nodes. If your tumor is small, it can be treated with a lumpectomy, or if your doctors are not yet sure if you will need chemotherapy, it is better to wait until after the surgery to have chemotherapy.

Standard chemotherapy treatments are given on a variety of schedules including weekly, three weekly, monthly, or six weekly treatments. The schedules vary depending on the drugs that are being used. The three and four weekly schedules may be the most common. This means, for example, that you’ll get treatment every three or four weeks, in 21-day cycles or 28-day cycles. If it’s a 21-day cycle, you may come in for an infusion once every three weeks. On a 28-day cycle, on the other hand, you come in for treatment on day one and day eight, and then go two weeks with no therapy. That’s two weeks with therapy and two weeks off. During this time, your treatment may be all intravenous or a combination of intravenous medicine and a pill you can take at home. The treatments can last anywhere from 12 weeks to six months to a year. Dose dense scheduling means you receive the drugs every two weeks for four to eight cycles.

Treatment areas vary. In a hospital, there may be an entire floor for oncology patients or just a separate area of a larger floor. Chemotherapy can also be given in a private doctor’s office. Everyone in the department is aware that patients can have anxiety and tries to make the area as comfortable as possible. Since the process doesn’t involve machines, the chemo room doesn’t look as intimidating as the radiation area. The room is comfortably lit and often has television sets or stereos in it. You may have a room to yourself or may sit among several other patients who are receiving their treatments. You’ll usually sit in a comfortable lounge chair for the procedure. Many patients bring phones, iPads, laptops, books, drinks, or anything to help pass the time as pleasantly as possible.

Because the thought of chemotherapy can be frightening, it is a good idea to bring someone with you for your first treatment to see how it goes and to drive you home, if necessary. Then if the first treatment goes well and you feel all right afterward, you may not need anyone for the following treatments. Usually, if you start off feeling alright and your antinausea drugs are effective, you’ll get through the rest of the treatments with relative comfort.

Side Effects of Chemotherapy

Side effects vary according to the drugs used. The most immediate potential side effect can be caused by doxorubicin (Adriamycin), which can leak out of the vein and cause a severe skin burn that could require skin grafting. For this reason, it’s generally given in a specific way: avoiding weak veins and running in the IV with lots of fluids, so that it can’t cause as much harm if it does leak out.

A more common side effect seen with many types of chemotherapy is nausea and vomiting. Some drugs are worse than others. Unfortunately the ones commonly used for breast cancer, doxorubicin (Adriamycin) and cyclophospha­mide (Cytoxan), frequently cause those side effects. Taxanes (Taxol and Taxotere) tend to to provoke less nausea.

The timing of nausea differs as well. Cyclophosphamide starts about six to eight hours after treatment and lasts eight to 24 hours, while doxorubicin starts in one to three hours and lasts four to 24 hours. Acute vomiting, which usually occurs in the first 24 hours after a chemotherapy treatment, seems to be related to serotonin and responds well to serotonin inhibitors like dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran), and palonosetron (Aloxi). Dexamethasone (a steroid related to, but not the same as, those used illegally by athletes) is also helpful for acute vomiting.

Delayed nausea and vomiting are caused by something called substance P and occurs one to five days after therapy, with a peak effect around 48–72 hours, and responds to a drug called aprepitant (Emend). For treatments with high potential for nausea and vomiting, the National Comprehensive Cancer Network recommends starting drugs before chemotherapy with aprepitant, dexamethasone, and one of the serotonin inhibitors. You want to start the drugs before chemotherapy because once nausea has set in, it is much harder to control. If these approaches are not enough, dopamine antagonists (Metoclopramide, Prochlorperazine, domperidone, or Metopimazine) can be added to the serotonin inhibitors and steroids. Cannabinoid (dronabinol, marijuana) has also been used for both acute and delayed chemotherapy-induced nausea and vomiting, and studies show that it is very effective. It is also available as a pill (Marinol), which is legal everywhere but not as effective.

The final type of nausea and vomiting is anticipatory and occurs days to hours prior to chemotherapy. This means you have experienced nausea and vomiting in the past and now, just thinking about getting chemotherapy next week makes you nauseated today. This type can be controlled with benzodiazepines starting one or two days prior to treatment or behavioral techniques. These days most oncologists try to prevent nausea and vomiting in the first place. Make sure you discuss this aspect of your care with your doctor and nurse so you understand which drugs are being given to prevent nausea and why.

Weight Gain

Although the cause of weight gain with chemotherapy is not clear, there is no question that it is quite common. It is important to try to continue to get as much exercise possible—this includes just walking—during treatment. There are many clinical trials looking at the best way to help women exercise and gain as little weight as possible during and after treatment.

Effects on Appetite and Sense of Smell

Sometimes chemotherapy causes you to lose your appetite. Food may taste different to you and some chemicals interact badly with certain foods, though both loss of appetite and chemical interaction are less common with breast cancer drugs than with others. You may also experience sensitivity to peculiar odors. The National Cancer Institute publishes a helpful booklet for people whose eating is affected by their chemotherapy.  

Premature Menopause

Chemotherapy can create a transient or permanent chemically induced menopause, with hormonal changes, hot flashes, mood swings, and no periods. Age and type of chemotherapy are the strongest predictors of your likelihood of being put into menopause. The closer you are to natural menopause, the higher your risk. The average age of menopause is 51.

Hair Loss

Chemotherapy treatments used in breast cancer, as in many other cancers, often cause partial or total hair loss. This is somewhat predictable according to the drugs used and duration of treatment. Women who get doxorubicin as part of their treatment almost always lose their hair, usually within two to four weeks after the onset of treatment. You’ll wake up one morning and find a large amount of hair on your pillow or in the shower, or you’ll be combing your hair and notice a lot in your comb. This is almost always traumatic, so you might want to buy a wig before your treatment starts. You can ask your oncologist to give you a prescription for a “cranial prosthesis” (wig) and often insurance will cover it. Also, it isn’t only the hair on your head that falls out. Pubic hair, eyelashes and eyebrows, leg and arm hair—some or all of the hair on your body will fall out, although in most women the eyelashes and eyebrows only thin a bit. Most of the time that isn’t a big problem cosmetically—you can thicken your eyebrows with pencil, for example, and apply false eyelashes—but it can be startling if you’re not prepared for it.

It may take a while after the treatments have ended for your hair to grow back. A little down will probably appear even before your treatments have ended, and within six weeks you should have some hair growing in, though the time depends on how fast your hair normally grows. Often it comes back with a different texture—curly if it’s been straight. Eventually the curl relaxes and your hair returns to normal after several haircuts. It may come back in a different color, most commonly gray or black.

Sexual Problems

Some women experience sexual problems, often related to the vaginal dryness of menopause. You may also suddenly encounter problems with your diaphragm or an IUD due to dryness. In addition, there are the physical and psychological effects of the treatment. It’s hard to feel sexy when you are tired and bald. This is an important time to communicate with your partner about each other’s feelings and needs and to try to find a comforting compromise.

Fatigue

Fatigue is a common side effect. There are five factors that are often associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and low thyroid. These are all treatable, so be sure to get them checked out. Other possible causes can be infection, electrolyte disorders, and cardiac dysfunction. Moderate to severe fatigue is always worth discussing with your doctor.

There are two ways you can approach this fatigue: drugs and exercise. It may be hard to force yourself to exercise, but it can help. It also can help prevent weight gain.

Chemo Brain

There are many side effects of chemotherapy that we’re just beginning to acknowledge, either because they are subtle or because they take longer to materialize. One of these is the decreased cognitive function that many patients experience and have labeled “chemo brain.” They feel they are not as sharp as they were before their cancer treatment, multitasking is more difficult, and their brain does not function as efficiently. Read more about this in Collateral Damage.

Other Side Effects

Other common side effects include mouth sores, conjunctivitis, runny eyes and nose, skin, nail changes, diarrhea, and constipation. You may get headaches, which is often from the antinausea medication. Any of these can be mild or severe or anything in between.

The long-term side effects of chemotherapy include chronic bone marrow suppression and second cancers, especially leukemias. The risk of leukemia is small and probably worth the benefit of the treatment, but you need to be aware that it exists. Doxorubicin, in particular, can be toxic to the heart. Consequently, a patient on this drug may have more problems with coronary artery disease years later. Paclitaxel (Taxol) can cause a reversible, dose-dependent, cumulative neuropathya pins-and-needles sensation, often in the hands and feet, which can get worse with each dose but is generally, at least partially, reversible. Taxol can also cause hand-foot syndrome, an itchy rash on the palms of the hands and the soles of the feet. Docetaxel (Taxotere) also causes neuropathy but is generally milder than paclitaxel. Docetaxel also causes a unique syndrome of swelling and fluid retention; some fluid retention is fairly common but occasionally it can be severe. Fortunately this is reversible, but it takes a long time. A newer form of paclitaxel, nab-paclitaxel  (Abraxane) has been shown to be at least as effective and possibly more effective than paclitaxel and is used for metastatic breast cancer. Although it generally has fewer side effects than paclitaxel, the neuropathy can be worse.

There’s no way to know in advance how you’ll react to your treatments. So, while it’s important to be prepared for the possible side effects, it’s equally important not to assume you’ll have all, or even any, of them. Positive thinking, exercise, maintaining a healthy diet, and keeping up your normal activities can significantly reduce the side effects of chemotherapy. Most women are able to continue their normal lives and maintain their jobs with minor adjustments while receiving treatment. You won’t feel great, but you’ll be functional. At this point, adjuvant breast cancer chemotherapy should be tolerable and you should be able to function. If it’s not, ask your doctor or nurse for strategies to reduce the side effects. Many options are available.

You can find a chart that lists the different types of chemotherapy and their most common side effects here.

Frequently Asked Questions

My sentinel node biopsy showed that I have micrometastasis. Does this mean I need to have chemotherapy?

Diagnosing micrometastasis can be very difficult. This is because the pathologist needs to determine if what is being looked at are cells that were displaced during surgery or an actual spread of cancer cells. We have become increasingly aware that displacement during a sentinel node procedure or an axillary node procedure occurs more often than we thought. This displacement of cells is not the same as having metastasis and it does not require the treatment with chemotherapy that you would need if it an actual metastasis had occurred.

If only one or several clumps of breast cancer cells are found in a lymph node based on IHC staining only or RT-PCR only, and they measure less than .2 mm, they are considered isolated tumor cells and the nodes are still considered negative (pN(i+)). That's because these are thought to be cells that were dislodged during the sentinel node procedure and not cells that made it to the nodes on their own. Cancer deposits greater than 0.2 millimeters but less than two millimeters are considered micrometastasis and are termed pN1mi, while any that are bigger than two millimeters are considered pN1.

Only an expert in breast pathology can look at the cells and determine if it is truly micrometastasis or if it is cell displacement. Your next step should be to get a second pathology opinion. This second opinion should not come from a general pathologist but from a breast pathology specialist. There are many excellent breast pathologists throughout the country who can provide a second opinion. To get a second pathology opinion, you will need to have the hospital where you had your surgery performed send your slides to the pathologist you have selected.

You may also want to consider being seen at a multidisciplinary breast care center where you could not only bring your pathology slides and breast films for review, but be seen by a breast specialist, medical oncologist, and radiation oncologist. They would review your pathology slides and mammography images and then discuss as a group how they think you should proceed. To find this type of program in your area, contact the university-based hospital nearest you, the American Cancer Society, a local breast cancer support group, or one of the NCI-Designated Comprehensive Cancer Centers.

If there are indeed multiple areas of micrometastases, doctors would typically recommend chemotherapy because there would be concern that an invasion had been missed.

My oncologist has recommended that I take certain chemotherapy drugs. How can I learn more about those drugs and what side effects I’m likely to experience?

Different drugs cause different side effects. It is important for you to discuss these side effects and what you can do before treatment begins to help keep them at bay. You can find a list of chemotherapy drugs and their side effects here.

Do all women need chemotherapy?

Making the decision about whether to have chemotherapy is not always easy. It can be especially difficult for those women who have negative lymph nodes. We know that between 30 and 40% of women with negative lymph nodes will still get metastatic breast cancer—but we currently don't have a way to identify who these women are. If you are hormone-positive and have negative nodes, you may want to consider the Oncotype DX test. It is a genetic test performed on a piece of breast tissue that can assess whether a woman is at low, medium, or high risk for recurrence. You may also want to look at the National Comprehensive Cancer Network's breast cancer treatment guidelines.

Chemotherapy reduces the risk of recurrence by about a third. This means that the higher the chance of recurrence, the more beneficial the chemotherapy is likely to be for you. This is an important concept to understand when trying to weigh risks and benefits. Adjuvant! can help you and your physician calculate the benefit you will receive from chemotherapy. Cancer Profiler is another online tool you can use to understand your treatment options.

I was told I have lymphovascular invasion. Does this mean I need chemotherapy?

When a pathologist examines tissue removed during a lumpectomy or mastectomy, one of the things she looks to see is whether cancer cells are present in any of the blood vessels or lymphatic vessels. If they are, it is referred to as vascular invasion, lymphatic invasion, or lymphovascular invasion (LVI).

A woman can have lymphovascular invasion but not have positive lymph nodes. This could be because the invasion hasn't spread to the lymph nodes or because it has bypassed the nodes and moved on to other areas of the body.

When LVI is present, doctors assume this means the cancer has acquired the genetic mutation it needs to create its own blood vessels, a process called angiogenesis. Because a tumor that has the ability to create its own blood vessels may have already begun to spread cancer cells to other parts of the body, the presence of LVI is an indicator that treatment should most likely include chemotherapy or hormone therapy (if the tumor is hormone sensitive).