Metastatic Breast Cancer

Treatment Strategies

Through research and advances in treatment, women are living longer with advanced disease. New treatment options have been approved, and more are being studied in clinical trials. The primary goal of treatment for metastatic breast cancer is to control the growth of disease for as long as possible and to maintain a satisfactory quality of life. Many options are available, and the treatment for an individual woman depends on many factors, including:

  • The site or sites of metastasis
  • The hormone receptor (ER/PR) and HER2 status of the cancer
  • The rate at which the disease is progressing
  • Your age, overall health and menopausal status
  • The time since your initial diagnosis and treatment (if the metastasis is recurrent cancer)

Even though metastatic breast cancer involves cancer in an organ other than the breast, the cancer cells are still breast cancer cells, which means the same treatments used for earlier-stage breast cancer are used for metastatic disease. However, these treatments are often used for different purposes or with different goals. The options for treating metastatic breast cancer are hormone therapy, chemotherapy and targeted therapy. Surgery and radiation are typically not used as part of treatment for metastatic breast cancer. When either is used, it’s usually to relieve symptoms or to prevent complications. (See Managing the Symptoms of Your Disease).

Types of treatment

Hormone therapy

Hormone therapy, also known as endocrine therapy, is the recommended first choice for women with metastatic breast cancer that tests positively for estrogen and/or progesterone receptors (ER+ and/or PR+). Hormone therapy is also sometimes recommended if the hormone receptor status is not certain or is negative. This treatment is effective at slowing the growth of metastasis in ER+/PR+ breast cancer because it works by blocking the action or decreasing the amount of estrogen or progesterone, the very substances that fuel the growth of breast cancer cells in your body.

Several types of drugs can be used for hormone therapy, and they differ in how they work, who they can be used for, and what side effects they can cause. Your doctor will consider several factors when recommending the best type of hormone therapy for your particular case, including whether you are premenopausal or postmenopausal and whether you have received hormone therapy as a previous treatment for earlier-stage breast cancer (Table 1). Your doctor will discuss the advantages and disadvantages of these drugs so that you can decide together which treatment course is best for you.

Table 1. Hormone therapy options for metastatic breast cancer

Menopausal status Hormone therapy options
Postmenopausal
Aromatase inhibitors: This class of drugs may lower estrogen levels by keeping one enzyme (called aromatase) from changing other hormones into estrogen.
    ▪ anastrozole (Arimidex)
    ▪ Ietrozole (Femara)
    ▪ exemestane (Aromasin)
 
Selective estrogen-receptor modulators (SERMs): These work like ERDs and block estrogen from attaching to breast cells. But because they are “selective,” they allow estrogen to communicate with other cells (such as bone, liver and uterine cells) that also have estrogen receptors.
    ▪ raloxifene (Evista)
    ▪ tamoxifen (Nolvadex)
    ▪ toremifene (Fareston)
 
Estrogen receptor downregulators (ERDs): These drugs break down hormone receptors on cells to prevent estrogen from attaching. This keeps the cells from receiving the signal from estrogen to multiply.
    ▪ fulvestrant (Faslodex)
 
Androgen: This male hormone may inhibit tumor growth in some women by lowering the amount of estrogen in the body.
    ▪ fluoxymesterone (Halotestin)
 
Progestin: These drugs are a synthetic form of the hormone progesterone, which counteracts some of the effects of estrogen.
    ▪ megestrol (Megace)
 
High-dose estrogen: Rarely used now, this treatment may be tried if the cancer no longer responds to other hormone therapies.
    ▪ ethinyl estradiol
Premenopausal
Luteinizing hormone-releasing hormone (LHRH) agonists: Also known as gonadotropin-releasing hormones (GnRHs), these drugs lower the level of estrogen in women.
    ▪ goserelin (Zoladex)
    ▪ leuprolide (Lupron)
 
Progestin: These drugs are a synthetic form of the hormone progesterone, which counteracts some of the effects of estrogen.
    ▪ megestrol (Megace)
 
Selective estrogen-receptor modulators (SERMs): These work like ERDs and block estrogen from attaching to breast cells. But because they are “selective,” they allow estrogen to communicate with other cells (such as bone, liver and uterine cells) that also have estrogen receptors.
    ▪ raloxifene (Evista)
    ▪ tamoxifen (Nolvadex)
    ▪ toremifene (Fareston)
 
Androgen: This male hormone may inhibit tumor growth in some women by lowering the amount of estrogen in the body.
    ▪ fluoxymesterone (Halotestin)
 
High-dose estrogen: Rarely used now, this treatment may be tried if the cancer no longer responds to other hormone therapies.
    ▪ ethinyl estradiol

Chemotherapy

Traditional chemotherapy is another option to treat metastatic breast cancer, especially if the cancer is ER-negative or PR-negative, if multiple hormone therapies have failed, or when immediate response is necessary (i.e., visceral crisis). Many chemotherapy drugs are options for treating metastatic breast cancer. Chemotherapy is sometimes given as a single drug and sometimes as a combination of two or three drugs, either given together or one after another. Your doctor will discuss the advantages and disadvantages of these drugs so that you can decide together which treatment course is best for you.

Table 2. Chemotherapy options for metastatic breast cancer

Type of cancer Chemotherapy agent or combination
  Generic name Brand name (Abbreviation)
HER2- Often-used single agents  
  doxorubicin Adriamycin
epirubicin Ellence
liposomal doxorubicin Doxil
paclitaxel Taxol
docetaxel Taxotere
protein-bound paclitaxel Abraxane
capecitabine Xeloda
gemcitabine Gemzar
vinorelbine Navelbine
eribulin Halaven
Other single agents  
cyclophosphamide Cytoxan
mitoxantrone Novantrone
cisplatin  
carboplatin  
etoposide VePesid
vinblastine Velban
fluorouracil (5-FU) Adrucil
methotrexate various products
ixabepilone Ixempra
Often-used combinations  
cyclophosphamide, doxorubicin, fluorouracil (CAF/FAC)
fluorouracil, epirubicin, cyclophosphamide (FEC)
doxorubicin, cyclophosphamide (AC)
epirubicin, cyclophosphamide (EC)
doxorubicin and docetaxel or paclitaxel (AT)
cyclophosphamide, methotrexate (Folex), fluorouracil (CMF)
docetaxel and capecitabine  
gemcitabine, paclitaxel (GT)
Other combinations  
ixabepilone and capecitabine  
HER2+ trastuzumab plus preferred agents  
  pertuzumab (Perjeta) and docetaxel  
pertuzumab and paclitaxel (not approval indication)  
trastuzumab plus other agents  
paclitaxel (alone or with carboplatin)  
docetaxel  
vinorelbine  
capecitabine  
HER2+, previously treated with trastuzumab    
  lapatinib (Tykerb) and capecitabine  
trastuzumab and capecitabine  
trastuzumab and lapatinib  
trastuzumab and other agents  

Targeted therapy

Targeted therapy is treatment directed at genes, proteins or other substances that contribute in some way to the growth and development of cancer cells. Targeted therapy is personalized treatment, tailored to the individual characteristics of the breast cancer cells in your body. These agents slow the progression of metastatic disease by blocking signals from various proteins that stimulate the growth of new cells. Targeted therapy drugs in breast cancer are primarily anti-HER2 agents (which are likely to be effective for tumors that over-express the HER2 marker on the surface of their cells)as well as targeted therapies for hormone receptor-positive patients.

Table 3. Targeted therapy options for metastatic breast cancer

Targeted therapy agent Type of metastatic breast cancer Approved/recommended treatment Notes
trastuzumab (Herceptin) HER2+ In combination with paclitaxel for first-line treatment
 
As a single agent after failure of one or more chemotherapy regimens
Approved for use in 1998
lapatinib (Tykerb) HER2+ In combination with capecitabine after failure of anthracyclines, taxanes (paclitaxel or docetaxel) and trastuzumab Approved for use in 2007
HER2+ and hormone receptor positive In combination with letrozole (Femara) Approved for use in 2010
pertuzumab (Perjeta) HER2+ In combination with trastuzumab and docetaxel Approved for use in 2012
ado-trastuzumab emtansine (Kadcyla) HER2+ As a single agent after failure of trastuzumab and taxanes Approved for use in 2013
everolimus (Afinitor) Hormone receptor positive, HER2- In combination with exemestane (Aromasin) Approved for use in 2012

Resistance to treatment

Resistance – when breast cancers that have been responding to therapy begin to grow again – may be caused by several factors. Sometimes it’s common after particular types of drugs (for example, anthracyclines, hormone therapies and taxanes), and sometimes it occurs after long-term exposure to a certain drug.

Researchers have begun to focus on how to overcome resistance, and some combinations of different kinds of drugs – such as a targeted drug and a chemotherapy drug – delay the time to disease progression. Researchers are also evaluating the order drugs are given in – known as sequential treatment – to see if one order produces better results than another. At the same time, research is ongoing to learn how breast cancer cells become resistant so that new drugs can be developed to overcome resistance and offer new options to women with breast cancer.

Choosing treatment

Choosing a treatment can be challenging because of the number of options, but if the first treatment doesn’t work, other treatments can be tried. Your doctor will talk to you about the various options for your particular type of breast cancer, and you should learn as much as you can about each option.

In deciding on a treatment, it’s important to think about your personal priorities. Some women want the most aggressive treatment available, and other women want to focus on supportive care. Communicate your priorities to your doctor. While he or she will make recommendations, the final decision is yours. Note, too, that your priorities may change over time as you continue through treatment, so talk to your doctor about these changes.

Some women prefer to take a break from treatment if their disease has stabilized and their quality of life is good. If you think you may wish to do this, talk to your doctor about the benefits and risks.

The choice to stop treatment permanently is not an easy one, but at some point, it may seem like the right decision for you. If you decide to stop treatment directed at the metastatic disease, it’s important to receive palliative care, which is treatment designed to help you live more comfortably. You should consider receiving palliative care as part of hospice care. Most people misunderstand hospice care and do not appreciate its value. Hospice is not about dying; it’s about living with a higher quality of life. Hospice care can often be delivered in your own home and provides pain relief and other supportive care as well as psychological, spiritual and logistical support for you and your family and help with daily living tasks. Most people have reported that once they started hospice care, they regretted not choosing it sooner.

Clinical trials

New treatments and combinations of treatment for metastatic breast cancer are being evaluated in clinical trials. All women with metastatic breast cancer should talk to their doctor about the possibility of participating in a clinical trial. Participating is a personal decision, so carefully weigh all the options before making this decision.

You can search for clinical trials on a number of websites:

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 Sources of Information

 

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