FAQs about Metastatic Disease

This content has been reviewed and approved by

William J. Gradishar, MD FACP
Director, Breast Medical Oncology, Professor of Medicine
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine

Prognosis

It is not uncommon to have survival spanning over several years with spread confined only to bone. Cancer can be slow growing in most patients with hormone receptor-positive disease. There are other patients who have metastases to skin or soft tissue only without any bone or organ involvement that can do even better. It is important to emphasize that there is tremendous variation in how breast cancer can behave in various patients, and no woman should extrapolate her outcome based on somebody else's experience.

There are many treatments for brain metastases. If it is in a single spot in the brain, your doctor may consider a neurosurgical evaluation to remove the abnormal spot. If there are 2 to 3 areas that are small, you may be a candidate for gamma knife, which is a very focused radiation treatment directed at these areas only. After either of these treatments, you may be a candidate for whole-brain irradiation to make sure that any other areas that were not visible are also treated. Your oncologist, in conjunction with the radiation oncologist, should discuss these issues with you.

Tamoxifen

I had cancer removed from my left breast 8 years ago and did not receive any other treatment. My doctor has just put me on  tamoxifen when he discovered that my cancer has spread to my spine and left side ribs. Is that the best treatment?

Your doctor must have tested your tumor and found it to be hormone receptor-positive, which means you are a candidate for antihormonal therapy. There are many different options for antihormonal therapy, which can be used in sequence should one stop working.

Hormone receptor-positive breast cancer responds to many treatments before we switch to chemotherapy or some other form of treatment. Your doctor will be following you with physical examinations and scans periodically to see whether you are responding to tamoxifen or not.

If you do respond, this treatment is as good as any other. If you do not, he or she will have other options, and will switch you to some other treatment, such as an aromatase inhibitor if you are postmenopausal (Arimidex^® [anastrozole], Femara^® [letrozole], or Aromasin^® [exemestane]), after which you could go on an injection of Faslodex^® (fulvestrant) and then onto subsequent forms of antihormonal therapy. The fact that you have relapsed so many years after your primary treatment may suggest that your tumor is slow growing.

Femara

My doctor has just put me on Femara^® (letrozole) after I finished 5 years of tamoxifen. Is it necessary?

It has been shown in a large randomized trial that 5 years of letrozole after initial treatment with 5 years of tamoxifen is better than having received 5 years of tamoxifen alone. After these results were reported, women who had been on placebo were given the option to start taking letrozole.

Women who agreed to do so had relatively larger tumors, a greater number of positive lymph nodes, and other high-risk factors compared with those who declined. After 2 years of letrozole use and despite up to a 2½-year break after stopping tamoxifen, these women had fewer relapses and fewer new primaries in the breast as well as a better chance of survival compared with the group that had declined to take Femara^® (letrozole). 

Arimidex

I have been taking Arimidex^® (anastrozole) after adjuvant chemotherapy for breast cancer for about 5 years. Should I stop taking it as my physician advises? 

You should take the advice of your physician. Anastrozole was compared with tamoxifen alone or in a combination of tamoxifen with anastrozole in a large randomized trial involving 9,000 women. That trial established the superiority of single-agent anastrozole and made it one of the standard approaches in treatment of postmenopausal woman with hormone receptor-positive early-stage breast cancer. There are some recent efforts to study additional benefit after 5 years of aromatase inhibitor, but those data are not mature yet.

Faslodex

I have heard there is an injection that can be taken only once a month instead of my hormone therapy pill every day. Can you tell me more about it?

That injection is called Faslodex^® (fulvestrant) and is given intramuscularly every 4 weeks. There are pros and cons of switching to injection versus continuing to take the pill. If you are on the pill as part of your treatment for early-stage breast cancer, then you should continue with it because fulvestrant is not approved therapy for that situation.

However, if you are on the pill for advanced breast cancer there still may be a reason to continue the pill for now if you are benefiting from it and save fulvestrant for later. If you forget to take your pill frequently or are having problems with this pill then you should discuss it with your doctor who may endorse fulvestrant as the appropriate therapy in your situation.

Chemotherapy

I have seen two different medical oncologists who have recommended two different chemotherapies for advanced disease. How do I know which one to take?

There is no single "gold standard" chemotherapy approach to metastatic breast cancer. Treatments are chosen for their side effect profile, ease of administration, cost and convenience, as well as individual preference of the treating physician and the patient. You should discuss these factors in detail with your treating physician to see which one is right for you. It may give you some comfort to know that you have many options to choose from and there may not be any right or wrong decision.

Assuming that tamoxifen is your first-line antihormonal therapy for hormone receptor-positive breast cancer that has spread to your bones, patients like you can respond to multiple lines of antihormonal therapy before they go to chemotherapy. It should be encouraging for you to know that women quite frequently live for many years with this type of metastatic breast cancer.

When you stop responding to tamoxifen, you can be switched to another form of antihormonal therapy, for example, an aromatase inhibitor if you are postmenopausal (examples would be Aromasin^® [exemestane], Femara^® [letrozole], or Arimidex^® [anastrozole]). It is only after failing multiple lines of endocrine therapy, or if the pace of disease progression increases, that your oncologist would consider chemotherapy.

I am assuming the tamoxifen is your first-line antihormonal therapy for hormone receptor-positive breast cancer that has spread to your bones. Patients like you can respond to multiple lines of antihormonal therapy before they go to chemotherapy. It should be encouraging for you to know that women quite frequently live for many years with this type of metastatic breast cancer.

When you stop responding to tamoxifen, you can be switched to another form of antihormonal therapy, for example, an aromatase inhibitor if you are postmenopausal (examples would be Aromasin^® [exemestane], Femara^® [letrozole], or Arimidex^® [anastrozole]). It is only after failing to respond to multiple lines of antihormonal therapy, or if the pace of disease progression increases, that your oncologist would consider chemotherapy.

For metastatic breast cancer, there is no usual fixed duration. Treatment is often continued for as long as the patient can tolerate it or until the disease stops responding, whichever comes first. Randomized trials looking at the optimal duration of treatment have shown that giving a break after 6 months of treatment does not compromise survival and results in fewer side effects.

However, the disease progresses sooner than one would expect compared with patients who continue to remain on chemotherapy. Paradoxically, in one study when patients were surveyed about the quality of life, those receiving chemotherapy ranked their quality of life superior compared with those who were on a break from chemotherapy and were not experiencing the side effects. This suggests that patients may feel more secure while receiving chemotherapy continuously.

For metastatic breast cancer, there is no usual fixed duration. Treatment is often continued for as long as the patient can tolerate it or until the disease stops responding, whichever comes first. Randomized trials looking at the optimal duration of treatment have shown that giving a break after 6 months of treatment does not compromise survival and results in fewer side effects.

However, the disease progresses sooner than one would expect compared with patients who continue to remain on chemotherapy. Paradoxically, in one study when patients were surveyed about the quality of life, those receiving chemotherapy ranked their quality of life superior compared with those who were on a break from chemotherapy and were not experiencing the side effects. This suggests that patients may feel more secure while receiving chemotherapy continuously.

There is no standard chemotherapy approach to metastatic breast cancer. Treatments are chosen for their side effect profile, ease of administration, cost convenience, as well as individual preference of the treating physician and the patient. You should discuss these factors in detail with your treating physician to see which one is right for you. It may give you some comfort to know that you have many options to choose from and there may not be any right or wrong decision.

When we start chemotherapy for metastatic disease, we take baseline measurements of the tumor by physical examination and scans. Your oncologist will repeat these measurements periodically, usually every 2 to 4 months to make sure that the treatment is working. If the measurements decrease to a certain predefined level of shrinkage, it will be called a partial response; if the tumor completely disappears, it will be considered a complete remission, and if the measurements increased appreciably, it would constitute a progression.

Your treatment will be changed either upon progression or if you do not tolerate it well. However, you may be given a break after several months of therapy even if the treatment seems to be working. That is a decision between you and your oncologist that will made after discussion of the pros and cons of this approach.

Taxanes

Is Taxol^® (paclitaxel) better than Taxotere^® (docetaxel)? 

Both these drugs belong to a family called taxanes and have similar mechanism of action. However, there are differences in the structure leading to a different side effect profile and some differences in their effectiveness depending on how they are given. When the FDA-approved dose of paclitaxel was compared with the FDA-approved dose of docetaxel in a randomized trial involving more than 400 patients, it was shown that the docetaxel was more effective in shrinking tumors, prolonging time to progression, and even rendered a longer survival time.

This was achieved at the cost of more side effects in terms of dropping blood counts, having fever, infection, and more nausea, vomiting, fatigue, and fluid retention. In other trials, particularly early-stage breast cancer, it is not clear one drug is superior to the other.

Is there a "new" Taxol^® (paclitaxel) that is given more "quickly" with fewer side effects? 
 

You are referring to Abraxane^® (nanoparticle albumin-bound [NAB] paclitaxel), a new formulation of paclitaxel. It involves binding of this drug to a common protein, albumin, to make it soluble.

Previously, paclitaxel was mixed with the castor-oil derivative called Cremophor^®, which had side effects of its own. Cremophor caused allergic reactions and could potentially damage nerves and entrap the drug, hampering its delivery to the tumor cells.

To prevent the allergic reactions to Cremophor-based paclitaxel, high doses of steroids along with other drugs, such as Benadryl and Tagamet, needed to be given intravenously and the drug had to be infused more slowly, generally over 3 hours. NAB paclitaxel on the other hand can be infused over 30 minutes and does not require any premedications.

In addition, because of this different formulation, higher doses of paclitaxel can be delivered in the NAB paclitaxel form. In a randomized trial comparing 175 mg/m² of paclitaxel to 260 mg/m² of NAB paclitaxel, it was shown that NAB paclitaxel achieved a higher likelihood of shrinking the tumors and prolonging time to disease progression. Only your physician may decide which drug is best for your situation.

There are many ways to give paclitaxel that have been tested in clinical trials, although the original approval was for every 3-week delivery. It has been tested extensively in a weekly schedule as well as in every other week schedule and both were found feasible.

In a randomized trial comparing weekly paclitaxel to every 3-week delivery of paclitaxel in woman with metastatic (stage IV) breast cancer, it was shown that weekly delivery may achieve a higher rate of tumor shrinkage and may even prolong time to progression of disease. The side effect profile also changes and weekly delivery causes delayed hair loss, very little drop in blood counts, and perhaps more nerve damage, causing numbness and tingling in fingers and toes that can be severe in around 20 percent of patients.

Anthracyclines

I have had a heart attack. Can I still receive Adriamycin^® (doxorubicin)?

Doxorubicin has the potential to cause heart damage after certain cumulative dose has been reached. Heart function of patients is assessed before giving them doxorubicin. Your doctor should do the same and you should discuss it in more detail with him or her.

One should point out that a heart attack is usually due to impaired blood supply to a portion of the heart muscle, whereas doxorubicin can cause global weakening of the heart muscle, impairing its pumping action. These are, therefore, different mechanisms of heart damage, and a small previous heart attack may not necessarily preclude use of doxorubicin if the pump function of your heart is adequate. This is called "ejection fraction" and can be measured by an echocardiogram or MUGA scan. Your physician will order one of these tests to asses your heart function and tell you whether it is safe or not.

Capecitabine

I would like to take pills instead of IV chemotherapy. Do I have any options? 

There are many new chemotherapy drugs and new targeted therapies that are available in pill form. Some of the older chemotherapeutic agents, such as cyclophosphamide and etoposide are also available in the form of pills. Newer drugs include Xeloda^® (capecitabine), which has been approved for breast cancer in patients who have previously received anthracycline (doxorubicin-like drugs) or taxanes (paclitaxel or docetaxel). You should, however, discuss it in more detail with your physician who will be the best person to guide you through this decision.

Gemcitabine

I don't want to lose my hair. Do I have any options in chemotherapy? 

Many chemotherapy drugs are largely devoid of the side effect of hair loss. You have many options, such as Xeloda^® (capecitabine), Gemzar^® (gemcitabine), Navelbine^® (vinorelbine tartrate), and Doxil^® (liposomal doxorubicin). In addition, when Taxol^® (paclitaxel) or Taxotere^® (docetaxel) are given weekly, hair loss is delayed.

If you are HER2 positive, you could receive Herceptin^® (trastuzumab), which is a monoclonal antibody and also does not cause any hair loss when administered alone. Another antibody, Avastin^® (bevacizumab) (if you are HER2 negative), may be an option for you as well. You should discuss your options in detail with your oncologist, who is the best judge for making a decision in your individual situation.

Many chemotherapy drugs are given weekly, and you could be a candidate for them if you have not previously received them. These include Navelbine^® (vinorelbine tartrate), Gemzar^® (gemcitabine), and weekly schedules of a different taxane, such as Abraxane^® (NAB paclitaxel) or Taxotere^® (docetaxel). However, it is important to point out that every drug is different, and there is no inherent magic in weekly delivery of therapy that applies to all drugs. You may have other options that do not need to be given this frequently that could be even more convenient for you. 

Avastin

My doctor gives me Avastin^® (bevacizumab) with my chemotherapy. Is that a good idea?

Your doctor must have recommended it because he or she felt that you will benefit from it. Bevacizumab has been shown to add effectiveness to Taxol^® (paclitaxel) in metastatic breast cancer. It is being tested with other chemotherapy drugs in this setting and has been tested with other drugs in different tumor types, such as colon and lung cancer, and has been found to be beneficial. It acts by blocking tumor cells from forming new blood vessels, thus impairing the ability of the tumor to grow.
 
I am HER2 positive. Can I receive Avastin^® (bevacizumab) with my chemotherapy? 

You may be able to in the future, but the drug is not FDA-approved yet to treat those with HER2 positive. The trial of bevacizumab plus Taxol^® (paclitaxel) versus paclitaxel alone mostly included patients who were HER2 negative. In fact, it excluded HER2-positive patients unless they had contraindications for receiving trastuzumab.

If you are HER2 positive, the antibody of choice for you is Herceptin^® (trastuzumab). However, if you have previously received trastuzumab and stopped benefiting from it, or if you have a contraindication to trastuzumab—such as abnormal heart function—you can discuss the use of bevacizumab with your oncologist.

Bevacizumab, when added to Taxol^® (paclitaxel), doubled its ability to shrink tumors and also nearly doubled the time to progression of disease. You should discuss the side effects and risks of bevacizumab with your oncologist and make sure you undergo appropriate testing, such as MRI of the brain to rule out any spread to the brain before you start this therapy.

Toxicity/Risks

What are the risks of Avastin^® (bevacizumab)? 

In general, bevacizumab is a well-tolerated antibody, which is devoid of the typical effects of chemotherapy, such as hair loss, nausea, vomiting, or lowering of blood counts. However, it can cause high blood pressure or may increase your need for high blood pressure medicines if you already have that condition. It can also cause some protein in urine, necessitating monitoring of your urine protein by your physician. There is a small risk of bleeding or forming clots with this drug, which you should discuss with your doctor. You should have a full discussion about the risks and benefits of this drug with your oncologist before you agree to go on it.

He or she may not be worried about the spread to your brain, but wants to definitively rule it out to avoid the potential risk of bleeding in the brain while undergoing treatment with bevacizumab in case such a spread does exist. In the early testing of bevacizumab, there were rare reports of such bleeding in patients whose cancer had spread to the brain, necessitating a cautious approach.