Advanced Breast Cancer

Treatment strategies

Treatment strategies will vary depending on your unique situation. A key in determining treatment options is the estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) status of the breast cancer, and sometimes a biopsy of the recurrence is needed. You and your doctor will evaluate your treatment options based on the following factors:

  • An initial or a recurrent diagnosis
  • The site(s) and extent of metastasis
  • Your age, menopausal status (if applicable) and overall health
  • The progression rate of the disease
  • Previous treatments, if any, and your response to them

Your doctor may talk with you about a treatment plan that includes a combination of systemic therapies, such as hormone therapy, chemotherapy and targeted therapy. Radiation therapy or surgery may be recommended for specific situations. You may be a candidate for clinical trials, which can give you access to the most innovative treatments, such as immunotherapy, that are in development.

Once you feel educated about your options, consider seeking a second opinion from another doctor who has experience treating late-stage breast cancer. Different opinions about the best treatment plan may exist, and it is important to make an informed decision. Regardless of which path you choose, palliative care, which helps relieve symptoms and side effects, should be a part of your discussion.

Types of treatment

Hormone therapy

Hormone therapy, also known as endocrine therapy, is the primary choice to treat tumors that are ER+ or PR+. The ER+/PR+ designation means that the cancer cells are stimulated to grow by exposure to the female hormones estrogen and/or progesterone. Hormone therapy acts to shrink tumors by either lowering the amount of estrogen in your body or blocking estrogen to slow or stop the growth of cancer cells.

Many types of hormone therapy drugs are available (see Table 1). Your doctor will work with you to determine which drug or combination of drugs may work best for you. Previous treatment(s) and your menopausal status are two factors that will influence your doctor’s treatment recommendation. Patients are typically continued on hormonal therapy as long as the cancer is not growing and being tolerated well. If the tumor grows, other hormonal options may be available. Sometimes, chemotherapy may be recommended either initially or after progression. Also, certain hormonal therapies are sometimes given in combination with biological therapies.

Table 1. Hormone therapy options

Premenopausal
Drug Category
tamoxifen Selective estrogen receptor modulator (SERM)
goserelin (Zoladex), leuprolide (Lupron) Luteinizing hormone receptor hormone (LHRH)
megestrol acetate (Megace) Progestin
fluoxymesterone Androgen (male hormone)
Postmenopausal
Drug Category
anastrazole (Arimidex), exemestane (Aromasin), letrozole (Femara) Aromatase inhibitor
tamoxifen, toremifene (Fareston) Selective estrogen receptor modulator (SERM)
fulvestrant (Faslodex) Selective estrogen receptor degrader
megestrol acetate (Megace) Progestin
ethinyl estradiol Estrogen
fluoxymesterone Androgen (male hormone)

 

Chemotherapy

Chemotherapy is a treatment option if your cancer cells are triple negative (ER-, PR- and HER2-) or if hormone therapy is unsuccessful. Chemotherapy is also usually given with anti-HER2 biological therapies for HER2+ breast cancer. Chemotherapy is typically given as a single drug (see list above right) or in cases of more rapidly growing, very symptomatic or higher burden of tumor, as a combination of two drugs. Your doctor will discuss the potential side effects of different chemotherapy drugs with you so you can weigh the advantages and disadvantages of this type of treatment. For some Stage III breast cancers, ovarian suppression with endocrine therapy may be recommended. As long as the cancer does not grow, or the side effects are tolerable, then treatment is continued. However, if the tumor grows or side effects are too severe, then another chemotherapy option may be discussed.

 

Common chemotherapy options

  • capecitabine (Xeloda)
  • carboplatin
  • cisplatin
  • docetaxel (Taxotere)
  • doxorubicin (Adriamycin)
  • epirubicin (Ellence)
  • eribulin (Halaven)
  • gemcitabine (Gemzar)
  • ixabepilone (Ixempra)
  • liposomal doxorubicin (Doxil)
  • paclitaxel (Taxol)
  • protein-bound paclitaxel (Abraxane)
  • vinorelbine (Navelbine)

Targeted Therapy

Targeted therapy strives to slow the progression of metastatic disease by pinpointing and blocking the genes, proteins or other substances that contribute to the growth and development of cancer cells. With this type of treatment, your doctor “targets” a drug to your specific receptor status. Targeted therapy is typically used for HER2+ breast cancer, with the anti-HER2 agents usually combined with chemotherapy. Other targeted agents are sometimes used in combination with hormonal therapy for ER+ or PR+ breast cancer (see Table 2). There are currently no approved targeted drugs for triple-negative breast cancer.

A class of drugs currently being explored is poly (ADP-ribose) polymerase (PARP) inhibitors. PARP is an enzyme that cancer cells use to repair DNA damage. PARP inhibitors are designed to disable those enzymes and enzymes damaged by chemotherapy. PARP inhibitors also promote cancer cell death and make cancer cells more sensitive to other chemotherapy agents, increasing the effect of chemotherapy drugs.

Table 2. Targeted therapy options

Targeted therapy agent Type of breast cancer Approved/recommended treatment
everolimus (Afinitor) ER+/PR+, HER2-, metastatic In combination with exemestane (Aromasin) for postmenopausal women who have already been treated with letrozole or anastrozole
palbociclib (Ibrance) ER+, HER2-, metastatic In combination with letrozole for postmeopausal women as a first hormone-based therapy
ado-trastuzumab emtansine (Kadcyla T-DM1 HER2+, metastatic For women previously treated with trastuzumab and a taxane, separately or in combination
lapatinib (Tykerb) HER2+, metastatic In combination with capecitabine (Xeloda) or trastuzumab (Herceptin), typically after treatment with trastuzumab-based therapy and ado-trastuzumab emtansine
pertuzumab (Perjeta) HER2+, metastatic, or as neoadjuvant therapy In combination with trastuzumab and docetaxel in individuals who have not been treated with anti-HER2 therapy or chemotherapy
trastuzumab (Herceptin) HER2+, metastatic In combination with paclitaxel as first-line treatment, with other chemotherapy drugs, or with lapatinib for later lines of therapy; as a single agent in patients who have received one or more chemotherapy regimens
 

Surgery

Surgery, the primary treatment for early-stage breast cancer, is used less often to treat advanced breast cancer because the cancer cells have spread to more than one site. Surgery is sometimes used in conjunction with other treatments to enhance quality of life (not cure the disease).

Radiation

Radiation is commonly used for brain metastases — either focused on one or several areas for smaller tumors (known as stereotactic radiation, or gamma knife), or to the whole brain. Other sites, such as the bone, can be treated if there are symptoms that don’t respond to medical therapy.

Resistance to treatment

Resistance occurs when breast cancers that were responding to therapy begin to grow again. Resistance may be caused by several factors; sometimes it occurs after a particular type of drug therapy or long-term use of a drug, and sometimes a tumor may be naturally resistant to systemic therapy. The promising news is that if disease progresses during treatment, alternative treatments with a different drug may be an option.

Overcoming drug resistance is a focus in breast cancer research. Scientists are studying different drug combinations, developing new drugs and evaluating the order in which drugs are given (sequential treatment).

Palliative care

Pain, fatigue, nausea and neuropathy are common side effects you may experience from your treatments or the cancer itself. Unmanaged pain can affect your ability to function, your appetite, your sleep and your mood, all of which can have a substantial effect on your quality of life. Ask your doctor about palliative care early on to help manage symptoms, as this has been shown to improve not only quality of life, but even length of life.

Often mistaken for hospice care, palliative care accompanies your regular treatment and provides physical and emotional relief. The doctors, nurses, social workers, psychiatrists, dietitians and chaplains who make up your treatment team will work with you to improve your quality of life, which will also benefit your caregivers and loved ones.

Immunotherapy

This treatment, also called biologic therapy, is still in the early experimental stage for breast cancer treatment. This approach uses the body’s own immune system to fight cancer cells. Important clinical trials are ongoing with promising early responses.

The immune system naturally protects the body by attacking germs, but cancer cells have a unique ability to withstand those attacks and to dampen the immune system. Immunotherapy focuses on combining the body’s natural defenses and works to block the immune-dampening mechanisms (known as “checkpoints”) with drug therapy to stop or slow the subsequent growth of cancer cells. Something that separates immunotherapy from traditional treatments is its “memory”— its ability to remain effective for long intervals far beyond the end of treatment.

Cancer vaccinations have been an ongoing topic of research for decades, but scientists have yet to develop one that is effective for breast cancer, especially when advanced disease is already present. Vaccinating patients with no cancer or early-stage breast cancer to prevent metastatic disease currently is being explored.

Successes in treating melanoma and lung cancer with immunotherapy have encouraged scientists to continue studying ways to treat advanced breast cancer with immunotherapy.

Choosing the right path for yourself

Undergoing continuous treatment can take a toll on you. You may reach a point where you feel you need a break, or you might be enjoying a good quality of life and choose to forgo treatment for a while. Talk with your doctor to ensure you understand the pros and cons of interrupting your treatment plan, even for a short time.

You will receive input from your doctors, nurses, family members and friends, but remember — the decisions are yours to make. Weigh the pros and cons of treatments, their corresponding side effects and how they fit into your idea of a good quality of life. Keep in mind that the treatment you choose initially may need to be adjusted depending on how your body responds and the progression of the disease. Unfortunately, there is no instruction manual.

If you reach a time when you choose to stop treatment altogether, talk with your doctor about your feelings. If you make that difficult decision, you are strongly encouraged to investigate hospice care, where efforts are focused on managing symptoms and supporting the patient and family, but not using cancer therapies. Hospice care can take place at home or in a hospice center and offers physical, emotional and spiritual support for you and your loved ones.

Clinical trials

Clinical trials are research studies that explore whether a medical strategy, treatment or device is safe and effective for humans. These studies also may show which strategies work best for certain illnesses or groups of people. Because current treatments are very unlikely to cure advanced breast cancer, patients are encouraged to think about taking part in clinical trials.

Many falsehoods about clinical trials persist because people typically don’t learn about clinical trials until they’re faced with considering them as a treatment option. Read on to discover key information you should know to help you make an informed decision about participating in a clinical trial. Be sure to read Myth vs Fact below, which addresses several misconceptions about clinical trials.

  • Benefits. All the advances in cancer treatment that are saving lives today have come directly from clinical trial research. As a volunteer, you are carefully monitored. You are guaranteed to receive the current standard of care during the trial. Additionally, by simply participating, you are making a valuable contribution to cancer research.
  • Types. Patients with advanced breast cancer may consider therapeutic trials and quality-of-life trials. Therapeutic trials determine if new treatment options are better than current treatment options, while quality-of-life trials study ways to improve the quality of life for people with cancer. There are also non-treatment trials that analyze tumor or blood specimens and those that ask for completion of questionnaires and medical information.
  • Timelines. The four phases of therapeutic clinical trials can take several of the 10 to 15 years it takes for a single drug to be developed. You may be part of a single phase or multiple phases of a trial.
  • Costs. Patient care costs include those related to doctor visits, hospital stays and some testing procedures that are part of standard care, which would be incurred if you did not participate in the trial and chose standard treatment. You are responsible for those, and they will be covered by your insurance as outlined in your plan. The Affordable Care Act requires all insurance companies to cover the routine patient costs from in-network providers associated with an approved clinical trial. An approved trial is defined as a trial in any phase that is aimed at preventing, detecting or treating cancer. Research costs, which are directly related to the clinical trial and include drugs and procedures, are typically covered by the trial sponsor. Always explore your plan benefits with your insurance company before volunteering for a clinical trial. The consent form that patients sign to participate in the trial always contains a section on which costs are covered by the trial and which are the responsibility of the patient or the patient’s insurance.
  • Safety Measures. All clinical trials are regulated by the U.S. Food and Drug Administration, with several safeguards in place to protect the safety of all participants. Every participating clinic, hospital, university and cancer center, regardless of location, must follow the same set of rules, known as protocols, that is developed for each study, along with an informed consent form, both of which have to be approved by a special group known as the Institutional Review Board. Protocols ensure consistency in eligibility criteria, tests and procedures performed, medications and doses, and study length. Throughout the clinical trial process, safety checks are done to ensure that the potential health benefits of a drug continue to outweigh the risks. If a safety issue arises, the trial is delayed or stopped.
  • Resources. Your treatment team members can give you more information about clinical trials in your area, but they may not be aware of all the trials available in other locations. Using online tools, such as Metastatic Trial Search (see below), makes it easy to search for trials that apply to you. (See Find a clinical trial below and Additional Resources)
 

Introducing metastatic trial search

Metastatic Trial Search is the first-ever clinical trial search designed for people with metastatic breast cancer. Along with providing valuable general information about clinical trials, this easy-to-use tool filters through hundreds of research sites in the United States to find search results tailored to your situation. Here’s how it works:

  1. Visit BreastCancerTrials.org and click Get Started under METASTATIC TRIAL SEARCH.

  2. Enter your birth year, zip code, gender, breast cancer type, sites with current evidence of disease and menopausal status.

  3. Click Show Trials for a list of current trials that may be options for you.

Along with a brief summary of the trial, each listing contains links to learn what’s involved, whom to contact, how to find out if you qualify and if travel is required.

The BreastCancerTrials.org home page also offers the BCT Trial Alert and Match to Trial services. Simply enter your personal data to begin matching to available trials, or click to learn more. You’ll be prompted for what you need throughout the process, such as medical history and pathology reports. Don’t worry about having everything with you to get started — you can save your information and return at any time.

Clinical trials myth vs. fact

MYTH: Clinical trials are only for people who have no other options for treatment (a “last resort”).
FACT: Clinical trials of cancer treatment may be available for individuals with cancer of all types and stages.
 
MYTH: Clinical trials are not safe.
FACT: Clinical trials have many built-in safeguards to ensure that participants’ rights and safety are protected. These safeguards include an institutional review board, a data and safety monitoring board and an ongoing informed consent process.
 
MYTH: Clinical trials involve treatments with unknown safety and efficacy. 
FACT: Phase III clinical trials involve treatments that have been shown to be safe and effective in earlier phase trials. Phase III trials also include treatment with the standard of care, which has well-established evidence of safety and efficacy. Phase I and II trials are based on the results of preclinical trials showing the potential for efficacy and are carefully designed to ensure the safety of participants.
 
MYTH: Signing a consent form to participate “locks” you into staying in a trial.
FACT: Once you have signed a consent form, you are free to change your mind and not participate. You can also decide to drop out of a trial at any time for any reason.
 
MYTH: Some participants in a clinical trial will get a placebo (sugar pill) instead of treatment.
FACT: Participants in cancer clinical trials will receive the standard of care as a foundation and then the experimental treatment or a placebo will be added to it. They will never receive a placebo instead of cancer treatment.
 
MYTH: The cost of care in a clinical trial is not covered by health insurance.
FACT: Under the new health care laws, patient care costs (such as going to the doctor, any stays in the hospital or certain testing procedures) are covered by insurance. Research costs are those directly related to the study. It’s common, but not guaranteed, for the trial sponsor
to cover these costs. Insurance does not typically cover research costs.
 
MYTH: Participants in clinical trials are treated like “guinea pigs.” 
FACT: The overwhelming majority of clinical trial participants (97 percent) say they were treated with dignity and respect; 93 percent report having a positive experience in the trial.
 
MYTH: Clinical trials only take place at large hospitals or cancer centers.
FACT: Many clinical trials are now done at local hospitals, cancer centers and doctors’ offices.
 

Find a clinical trial

 

Questions to ask your doctor about treatment

  General questions
  • What are the results of tumor marker testing of my cancer (ER, PR and HER2 status)?
  • What treatment plan do you recommend? Why?
  • Are there any other treatment options available to me?
  • What is the goal of my treatment?
  • What are the possible side effects of this treatment?
  • How will this treatment affect my daily life and routine activities?
  • What clinical trials are open to me?
  Questions about hormone therapy
  • Which hormone therapy drugs can I take with my menopausal status?
  • What are the advantages and disadvantages of these drugs?
  • Which drug would be best for me? Why?
  • What are the possible side effects of this drug?
  Questions about chemotherapy and targeted therapy
  • What are the names of the drugs and how are they given?
  • Where will I receive treatment (in the doctor’s office, in a clinic)?
  • Will I need another person to help me get home after treatment?
  • How long will each treatment session last?
  • What is the difference between oral and IV medications?
  • What are the side effects of each drug?
  • What can be done to decrease these side effects
  • What is the likelihood of resistance developing?

Additional Resources

 

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