Patient education: Treatment of metastatic breast cancer (Beyond the Basics)

INTRODUCTION — 

The word "metastatic" describes cancer that has spread beyond its original location in the body. Metastatic breast cancer is cancer that started in the breast and spread to the lymph nodes or other organs such as the liver, lung, or brain. Most of the time, metastatic breast cancer cannot be cured. However, treatment can help you live longer, slow your cancer's progression, relieve your symptoms, and improve your quality of life. There are other terms used sometimes to refer to metastatic disease, such as "stage 4" or "advanced." However, "metastatic" breast cancer is more precise and will be used throughout this topic.

LOCAL RECURRENCE — 

Anyone who has been treated for breast cancer is at risk of a "local" recurrence. This is not the same as metastatic cancer; it means cancer that comes back in the breast, chest wall, or surrounding lymph node areas rather than a more distant part of the body, such as bone, liver, or lung. The exact site of a local recurrence may depend on how the original cancer was treated:

●For people who had breast-conserving treatment, meaning surgery to remove the cancer but not the entire breast, a local recurrence may occur in the breast. In some cases, this may be difficult to distinguish from a new, second cancer in the same breast. Your doctors may try to make this distinction if possible, since they might treat a new cancer differently than a recurrence, but it's not always possible to know.

●For people who had a mastectomy (surgical removal of one or both breasts), a local recurrence may present as a mass on the skin or chest wall.

People who had either type of surgery may also experience recurrence in the axilla (armpit area). A local recurrence should be distinguished from an entirely new breast cancer in the opposite breast, which is treated as such and is not considered a "recurrence" or a "metastasis" (when the original cancer spreads).

The approach to treating a local recurrence will depend on the size and location of your tumor, as well as whether or not you have had radiation therapy (RT). Your doctors and surgeons can talk with you to determine the most appropriate treatment plan. If surgery is not an option, radiation may be an alternative treatment.

METASTATIC DISEASE — 

As discussed above, the term "metastatic" means cancer that has spread to other parts of the body (eg, bone, liver, lungs, or more distant lymph nodes).

Goals of treatment — Unfortunately, few if any people with metastatic breast cancer will be cured, meaning that the cancer completely disappears and never comes back. However, there are treatment options that can help you live longer, relieve cancer-related symptoms, and improve your overall quality of life. The medical term for this is "palliation," but many doctors describe the goal as "keeping you feeling as good as you can for as long as you can."

Since the main goal of therapy is to get you feeling as good as possible, your oncologist (cancer doctor) will attempt to do so by recommending therapies that are most likely to work and have the fewest side effects. Available therapies can either be those that work in one area (called "local" therapies), such as surgery and/or radiation, and those that work everywhere in your body (called "systemic" therapies).

Systemic treatment — Systemic therapy includes the use of antiestrogen (more commonly called "endocrine") therapy, chemotherapy, and/or a drug that is a type of "targeted therapy," meaning it blocks a certain protein in cancer cells that is important for their survival and growth. The choice between the treatment options depends on where and the extent to which the cancer has spread, your overall health, and your symptoms.

In addition your treatment options will depend on the tumor's characteristics (estrogen receptor and human epidermal growth factor receptor 2 [HER2]) and whether certain genetic mutations are present.

●Status of hormone receptors – Some breast cancers have "receptors" to certain female hormones (estrogen or progesterone), meaning those hormones can increase their growth. These are referred to as estrogen receptor (ER)- or progesterone receptor (PR)-positive cancers. People whose cancer falls into this category tend to have better outcomes than those whose tumors are ER and/or PR negative. Additionally, people with hormone receptor-positive cancer are candidates for a type of treatment called endocrine therapy, but those with hormone receptor-negative cancer are not (since these medications do not work in this situation). (See 'Approach to treatment of hormone receptor-positive disease' below.)

●HER2 expression – Human epidermal growth factor receptor 2 (HER2) is a protein that is present in approximately one-fifth of all breast cancers. People with HER2-positive cancer are very likely to benefit from certain treatments that target this protein. (See 'Approach to treatment of HER2-positive disease' below.)

Hormone receptor and HER2 status should be reassessed if you have a relapse (recurrence) of breast cancer. This means checking hormone receptor and HER2 status again, even though this was probably done at the time of your initial diagnosis. This is because metastatic cancer can have different characteristics from the primary (original) breast cancer, and if this is the case, you may have different treatment options than previously.

The best approach to treating metastatic breast cancer depends on your situation, your preferences, and the specific characteristics of your cancer.

Approach to treatment of hormone receptor-positive disease — People with hormone receptor-positive, HER2-negative metastatic breast cancer who don't have severe symptoms, and do not have life-threatening disease or evidence of visceral involvement (tumors affecting certain vital organs), do not require initial chemotherapy and can be treated first with endocrine therapy.

The approach to patients with hormone receptor-positive, HER2-positive disease is discussed below. (See 'Approach to treatment of HER2-positive disease' below.)

Endocrine therapy — The goal of endocrine therapy is to prevent cancer cells from being stimulated by estrogen. Endocrine therapy is also known as "antiestrogen treatment." This includes:

●Selective estrogen receptor modulators (SERMs)

●Aromatase inhibitors (AIs)

●Selective estrogen receptor down-regulators (SERDs)

●Progesterone-like molecules (progestational agents)

●Other sex steroid hormones

Endocrine therapy is used in all people with hormone receptor-positive cancer, but different options are available depending on whether the person has already been through menopause (and whose ovaries are no longer producing estrogen):

People who have been through menopause or have had their ovaries removed may be treated with either tamoxifen or an aromatase inhibitor, as endocrine therapy. (See 'Tamoxifen' below and 'Aromatase inhibitors' below.)

People who have not yet been through menopause may be treated with tamoxifen. However, in some cases, strategies to stop the ovaries from making estrogen are used, in combination with either tamoxifen or an aromatase inhibitor (this kind of endocrine therapy is only used in people who have been through menopause or are on drugs that stop their ovaries).

Stopping estrogen production by the ovaries can be accomplished with surgery to remove the ovaries ("oophorectomy") or medications called gonadotropin-releasing hormone (GnRH) agonists (eg, triptorelin) and antagonists (eg, goserelin and leuprolide). Another form of endocrine therapy is achieved with selective estrogen receptor down-regulators, or SERDs, which are also usually given after a premenopausal person has either had oophorectomy or is treated with a GnRH agonist or antagonist.

Sequential endocrine therapies are typically used. Most clinicians will recommend chemotherapy only for people whose cancers progress after two or three trials of endocrine therapy and it appears that it will no longer work.

A targeted therapy may be recommended along with endocrine therapy. (See 'Treatments frequently added to endocrine therapy' below.)

Aromatase inhibitors — Aromatase inhibitors (AIs) are drugs that reduce estrogen levels in the body. They do this by blocking the protein that helps make estrogen outside of the ovary (aromatase). Medications in this class include anastrozole, letrozole, and exemestane. These agents are only effective in people who have already been through menopause; in fact, if the ovaries are functional (ie, the person has not yet gone through menopause), use of an AI can cause a paradoxical increase in estrogen levels (which is the opposite of the desired goal in breast cancer). If your doctor is not sure whether your ovaries are still producing estrogen, they may do blood tests or suggest medicine to suppress their function (or surgery to remove the ovaries altogether).

Side effects of AIs include hot flashes, weakening of the bones and bone fractures, and pain in the muscles and joints.

There is evidence that combining an AI with other kinds of drugs may be more effective than the AI alone. (See 'Treatments frequently added to endocrine therapy' below.)

Fulvestrant — Fulvestrant is a selective estrogen receptor down-regulator (SERD) and is another medication that blocks the influence of estrogen on breast cancer cells. It can be used when metastatic disease has progressed despite prior endocrine therapy, or as a first line of therapy in people who have been through menopause, or in premenopausal people if their ovaries have been removed or suppressed with medication. Because it is not absorbed when given orally, and because it disappears from the bloodstream very quickly after an intravenous (IV) injection, fulvestrant must be given as an injection into the muscle. This usually involves getting two simultaneous injections (one in each buttock) once a month. In some cases, fulvestrant may be given along with an AI. (See 'Aromatase inhibitors' above.)

Side effects of fulvestrant include hot flashes, increases in liver enzymes, injection site pain, and joint pain.

There is also another class of SERDs that can be taken orally. An example of this is elacestrant. The most common side effect of elacestrant is nausea, which occurs in approximately one-third of patients.

Tamoxifen — Tamoxifen is a type of drug called a selective estrogen receptor modulator (SERM). These agents block estrogen from stimulating breast cells.

Tamoxifen is a pill that you take by mouth. It is commonly used as a first-line endocrine therapy for premenopausal females and for males with advanced breast cancer.

Well over one-half of people with hormone receptor-positive breast cancer who take tamoxifen will have their disease stop growing or decrease in size. However, some do not respond at all to tamoxifen. Regardless, even if tamoxifen treatment is effective at first, almost all cancers will eventually stop responding.

A subset of people with metastatic breast cancer experience a disease "flare" within two days to three weeks after starting tamoxifen. This may cause an increase in bone pain, a high blood calcium level, and (in people with breast cancer involving the skin) skin redness or an increase in the size and/or number of skin nodules. These flares usually subside within four to six weeks. In the meantime, the symptoms can be treated with medications that reduce pain and lower blood levels of calcium. In severe cases, your doctor may tell you to temporarily stop taking tamoxifen until the flare subsides. Many doctors consider a flare reaction to be a sign that endocrine therapy is working.

Tamoxifen acts like an anti-estrogen against breast cancer and also in the brain; therefore, while it works against the cancer, it may cause hot flashes, as often happen with menopause. However, because of its estrogenic effect, it can slightly increase the risk of blood clots, uterine bleeding, and endometrial cancer, as does estrogen itself.

Sex steroid hormones — Progestins, estrogens, and androgens are all sex steroid hormones. They may play a role in the third- or fourth-line treatment of metastatic breast cancer (ie, they may be appropriate in situations in which other therapies have not been successful). However, these therapies are associated with relatively high frequency of bothersome side effects and they are rarely used in modern treatment of breast cancer.

Treatments frequently added to endocrine therapy — These are medications that target and interfere with the function of specific enzymes in the body. They include:

●Cyclin-dependent kinase (CDK) 4/6 inhibitors – These drugs include palbociclib, ribociclib, and abemaciclib; one of these medications may be given along with an AI or fulvestrant. (See 'Aromatase inhibitors' above and 'Fulvestrant' above.)

●Alpelisib – This drug may be added to endocrine therapies, particularly fulvestrant, for people whose tumors have a mutation in a gene called phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). (See 'Fulvestrant' above.)

●Everolimus – This is a type of medication called a mechanistic target of rapamycin (mTOR) inhibitor; it is sometimes used in combination with an AI or tamoxifen. (See 'Aromatase inhibitors' above and 'Tamoxifen' above.)

While effective, these combined regimens are typically associated with more side effects than seen with one agent alone. However, the addition of CDK 4/6 inhibitors has been particularly effective compared with endocrine treatment alone, and one of the available drugs is almost universally used either with the first or the second endocrine treatment. Of note, several studies have now demonstrated that people whose tumors progress on a first endocrine treatment/CDK 4/6 inhibitor do not benefit from continuing the CDK 4/6 inhibitor even though the second endocrine therapy is reasonably likely to be beneficial.

Chemotherapy — Chemotherapy is a different kind of treatment to attack cancer, and is typically used for people with hormone receptor-positive cancers after their cancer has progressed on multiple lines of endocrine therapy, or for those with cancer that is growing quickly or affecting organs like the liver or lungs, and for those with ER-negative cancers. Chemotherapy is discussed in more detail below. (See 'Chemotherapy' below.)

Approach to treatment of HER2-positive disease — People whose breast cancers produce high levels of the protein human epidermal growth factor receptor 2 (HER2) can benefit from treatments that target this protein. These kinds of cancers are called HER2-positive breast cancers and are typically treated with a HER2-directed agent plus chemotherapy, particularly if they are also hormone receptor-negative. (See 'Chemotherapy' below.)

For people with HER2-positive disease that is also hormone receptor-positive, HER2-directed therapy is typically given first with chemotherapy for several cycles and then with endocrine therapy. However, for some people whose disease is not causing significant symptoms or burden, a HER2 agent can be used with endocrine therapy as initial therapy. Endocrine therapies are discussed above. (See 'Endocrine therapy' above.)

There are several drugs that target HER2; these are discussed in more detail below. Your doctor will talk to you about whether HER2-targeted therapies (or combination of therapies) are options for you and help you decide on a treatment plan.

Trastuzumab — Trastuzumab is a "monoclonal antibody"; it can work by itself or in combination with endocrine therapy or chemotherapy. (See 'Chemotherapy' below.)

It is generally given IV once per week or once every three weeks. Trastuzumab can also be given subcutaneously (as an injection under the skin) rather than intravenously. The most common side effect is fever and/or chills. Heart failure develops in approximately 3 to 5 percent of people treated with trastuzumab. Trastuzumab-related heart damage may not be permanent, and improvements have been seen once trastuzumab is discontinued. Trastuzumab has almost no side effects except for occasional allergic reactions during infusion (which can be prevented in subsequent infusions). However, trastuzumab has been associated with congestive heart failure in a few cases, and caution should be used in giving it to people who are older adults or have a pre-existing heart condition.

Pertuzumab — Pertuzumab is a similar drug to trastuzumab. It has not been tested by itself, or by itself with other types of therapies like endocrine therapy or chemotherapy. However, when combined with chemotherapy and trastuzumab, pertuzumab is more effective than just chemotherapy and trastuzumab, and so it is often added to chemotherapy and trastuzumab. (See 'Chemotherapy' below.)

Like trastuzumab, it was originally given by intravenous infusion, but it can now be given in combination with trastuzumab subcutaneously. The side effects of pertuzumab are mostly gastrointestinal, especially frequent diarrhea, and these can often be controlled with conservative measures.

Ado-trastuzumab emtansine — This drug is called an antibody-drug conjugate (ADC). It contains a highly potent chemotherapy agent (emtansine) linked to trastuzumab, which is an antibody. This way, the trastuzumab carries the emtansine directly, and only, to cells that make HER2. Inside the cells, the emtansine is released to kill the cell. Ado-trastuzumab emtansine is only given by itself, intravenously, not in combination with other anti-cancer medications; it has been found to be effective even when trastuzumab itself does not work. In addition, it is just as effective as some combinations of trastuzumab plus chemotherapy. However, after the cancer cell dies, some of the emtansine does leak out into the surrounding tissue and the blood system, which can lead to more side effects than are seen with trastuzumab alone, most notably, low platelet counts (platelets are made in your bone marrow and stop bleeding) and damage to the nerves of the fingers and toes ("peripheral neuropathy").

Fam-trastuzumab deruxtecan — Like ado-trastuzumab emtansine, this drug is an ADC. It consists of a HER2 antibody (like trastuzumab) and a different chemotherapy drug than used in ado-trastuzumab emtansine, called deruxtecan, which is a topoisomerase I inhibitor. Ado-trastuzumab emtansine is a particularly effective agent. It works against cancers that are considered HER2-positive (meaning they make a lot of HER2), just like each of the agents discussed above, even when they quit or do not work.

Moreover, fam-trastuzumab deruxtecan also works against cancers that make a little HER2, but not enough to be considered HER2 "positive." These cancers are called HER2 "low."

Fam-trastuzumab deruxtecan is given intravenously every three weeks, and as with ado-trastuzumab emtansine, it is not given with other anti-cancer agents. Because some of the deruxtecan leaks into surrounding tissue and the bloodstream, it may cause gastrointestinal side effects and low white blood cell counts with risk of infection. Importantly, it can cause potentially fatal lung damage in some people.

Oral tyrosine kinase (TKI) inhibitors — These are drugs taken by mouth that block the effects of HER2. Drugs in this category include lapatinib, neratinib, and tucatinib. They are often used along with trastuzumab and/or a chemotherapy agent. Side effects may include skin rash, diarrhea, and nausea.

Approach to treatment of "triple negative" disease — People with HER2-negative, hormone receptor-negative (also called "triple-negative") metastatic breast cancer are typically treated with chemotherapy. The exact definitions of "negative" differ, ranging from having absolutely no trace of the proteins to low levels that are not high enough to be considered "positive." Strategies involving a combination of chemotherapy and immunotherapy, which harnesses the body's own immune system to fight cancer, are also starting to be used for treating triple-negative disease.

Chemotherapy — Chemotherapy is a treatment given to slow or stop the growth of cancer cells. Chemotherapy is not given every day but instead is given in cycles. A cycle is the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines. A typical cycle of chemotherapy is 21 or 28 days. Different drugs are given on different schedules; for example, a cycle could involve multiple daily or weekly doses, in many cases followed by a recovery period.

Chemotherapy is usually suggested in the following situations, depending on the receptor status of your cancer (see 'Systemic treatment' above):

●After your cancer has become refractory (resistant) to endocrine therapies, if you have ER-positive breast cancer

●Early on, if you have ER-negative breast cancer

●Frequently early on, with a HER2-directed agent, if you have HER2-positive breast cancer

Chemotherapy drugs may be given alone, one after another, or in combination. In metastatic breast cancer, a single chemotherapy agent is usually given. If it is effective, then that agent is continued; if not, your doctor might suggest trying a different chemotherapy agent.

However, in certain cases, especially if the cancer appears to be growing rapidly and is causing damage to certain organs (such as your lungs or liver), combinations of different chemotherapy drugs are used at the same time. Many times, these will be continued together for a while until the cancer is sufficiently shrunk so as not to be life threatening, and then one of the drugs is discontinued while the other is maintained.

There are a variety of chemotherapy drugs that can be used to treat breast cancer as single agents or in combination. Some are given by IV, and some as pills (orally). Some are more likely to cause bothersome side effects, such as hair loss, while others are less so. Nausea and vomiting used to be quite common with chemotherapy, but when a single agent is used, and in combination with modern antinausea drugs, this side effect has become less common. All chemotherapy suppresses bone marrow function; as new blood cells are made in the bone marrow, this means you will have fewer blood cells, which can lead to symptoms of anemia (such as fatigue) and temporarily make you more susceptible to infection. Different classes of chemotherapy agents may be associated with different side effects. You will be monitored closely while undergoing chemotherapy, so any side effects can be quickly identified and managed. Your doctor can talk to you about the best approach for your situation.

It is not clear how many cycles of chemotherapy are best for treating metastatic breast cancer. In general, overall survival is the same in people treated with continuous chemotherapy (repeating cycles until it becomes ineffective) or intermittent chemotherapy (giving several cycles and then stopping until the cancer progresses), although tumor growth may be slowed somewhat in people treated with continuous therapy. Intermittent chemotherapy may allow for a better quality of life, since it involves taking breaks from treatment. This may be a reasonable option if your cancer-related symptoms stay under control during treatment.

Immunotherapy — Immunotherapy, using drugs called "immune checkpoint inhibitors" (ICI), uses the body's own immune system to fight cancer. Immunotherapy, particularly with the antibody pembrolizumab, has been found to work in a subset of people with triple-negative metastatic breast cancer. It is given intravenously in combination with chemotherapy every three or six weeks (depending on the dose used).

Possible side effects of pembrolizumab are usually related to the immune system's effects on the body's organs. They can include fatigue, muscle pain, decreased appetite, itchiness, diarrhea, nausea, rash and constipation. However, the main concern in regards to any ICI is direct effect on normal organs, including the gastrointestinal system, liver, lungs, skin, and hormone glands. Chemotherapy has been the mainstay of treatment for triple-negative breast cancer. (See 'Chemotherapy' above.)

Other types of treatments

Therapies directed against BRCA mutations — Mutations in two genes, known as breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2), are associated with an increased risk of hereditary breast (as well as ovarian) cancer. (See "Patient education: Genetic testing for hereditary breast, ovarian, prostate, and pancreatic cancer (Beyond the Basics)".)

BRCA carriers with metastatic HER2-negative breast cancer who have a BRCA mutation and have already received chemotherapy may benefit from a medication called a poly(ADP-ribose) polymerase (PARP) inhibitor. There are two PARP inhibitors (olaparib and talazoparib) used for treatment of metastatic breast cancer in people who harbor a BRCA1 or 2 mutation. PARP inhibitors are taken orally without combination with other anti-cancer agents, and are approved for metastatic breast cancer that has progressed after treatment with chemotherapy (and, if the person has ER-positive breast cancer, after endocrine therapy). (See 'Endocrine therapy' above.)

Possible side effects include fatigue, anemia, low white blood cell counts and increased risk of infection, and occasional nausea, vomiting, and diarrhea. Both drugs have been associated with an increased risk of acute myelogenous leukemia, but this is rare.

Bone-modifying agents — Bone-modifying agents are not used to treat breast cancer directly; however, they can help prevent complications involving bones, such as fractures, spinal cord compression, and hypercalcemia of malignancy (in which there is too much calcium in the blood). Two classes of agents used are the bisphosphonates (pamidronate, zoledronic acid, clodronate, and ibandronate) and a medication called denosumab.

Of these, the most commonly used is zoledronic acid, which is given by IV over approximately 15 minutes. Pamidronate may be equally effective, but takes longer to administer (90 minutes) and thus is less convenient for most people. The main side effects of these drugs are occasional muscle and bone aches for a few days after the injection.

Studies have demonstrated that zoledronic acid can be given every three months, although in some situations (eg, people with extensive or symptomatic bone metastases), the schedule may start with monthly injections for six months before switching to every three months. In the past, these drugs were discovered to cause a problem called osteonecrosis of the jaw, in which bone cells in the jaw die due to lack of blood. However, subsequent studies have demonstrated that this complication is very rare when injections are spread out to every three months (versus continued monthly injections) and the person has healthy teeth.

Denosumab is a drug given as a monthly subcutaneous (under the skin) injection. It is as effective as the bisphosphonates, but is more convenient and may be less likely to cause the post-treatment aches and pains. However, it is much more expensive, and so many insurances require treatment with zoledronic acid first if possible.

Role of surgery or radiation therapy — Treatment to a specific lesion (mass) may be required if it is causing symptoms or there is a threat of complications (eg, a tumor compressing the spinal cord and causing a lot of swelling in the brain, or affecting the hip and raising the risk of fracture). This may require either surgery or radiation therapy (RT), or both, in the affected area. The exact approach depends on your situation and preferences.

The main goal in these situations is to alleviate particularly severe, urgent, or life-threatening complications of metastases in specific sites, such as in the brain, spinal cord, or bones. These therapies are most often recommended if systemic therapy (eg, endocrine therapy, chemotherapy, or targeted therapy) is not likely to work, or not likely to work quickly enough.

Some people will develop metastatic disease that is confined to one organ, such as one area of the liver or one lobe of the lung. In these cases, some doctors favor treatment directed at the tumor site. This may consist of surgical resection (to remove the affected part of the organ), targeted radiation, radiation frequency ablation, chemoembolization, or other methods. None of these have been shown to improve survival in metastatic breast cancer, and in one large trial evaluating radiation therapy in this situation (with all patients receiving systemic therapy), there was no benefit. Thus, these approaches are rarely used, although they may be appropriate in highly selected situations.

Your doctor can talk to you about whether you might benefit from a local treatment approach.

WHERE TO GET MORE INFORMATION — 

Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Breast cancer (The Basics)
Patient education: Mastectomy (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Breast cancer guide to diagnosis and treatment (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Treatment for hormone receptor-positive, HER2-negative advanced breast cancer
Overview of the approach to metastatic breast cancer
Endocrine therapy resistant, hormone receptor-positive, HER2-negative advanced breast cancer
The role of local therapies in metastatic breast cancer
Treatment of metastatic breast cancer in older women
Breast cancer in men
Use of osteoclast inhibitors in early breast cancer

The following organizations also provide reliable health information.

●American Society of Clinical Oncology

(www.cancer.net/portal/site/patient)

●National Cancer Institute 1-800-4-CANCER (226237)

(www.nci.nih.gov)

●American Cancer Society 1-800-ACS-2345

(www.cancer.org)

●National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)