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Metastatic breast cancer (also called stage IV or advanced breast cancer) is not a specific type of breast cancer. Stage IV or metastatic breast cancer is known as the most leading stage of breast cancer.

Stage IV breast cancer is breast cancer that has progressed beyond the breast and surrounding lymph nodes to other areas or parts of the body (most oftenly in the lungs, bones, liver or brain).

What is Metastatic Breast Cancer:

Although metastatic or stage IV breast cancer has progressed to other areas of the body, it’s still breast cancer and must be treated as breast cancer.

For instance, breast cancer that has progressed to the bones is still breast cancer (not bone cancer). The cells of breast cancer have invaded the bones. It’s not as common as cancer that begins in the bones. So, it should be treated with breast cancer medicines rather than medications for cancer that starts in the bones.

In case you’ve been diagnosed with metastatic or stage IV breast cancer, then you’re not alone. It’s estimated there were over 168,000 women living with metastatic or stage IV breast cancer in the United States in 2020 (most recent estimate available). Men can also get metastatic (stage IV) breast cancer.

When Can Metastatic Breast Cancer Occur:

Some individuals have metastatic breast cancer (also known as stage IV or advanced breast cancer) when they are initially diagnosed with breast cancer (approximately 6 % of diagnoses in females and 9 % of diagnoses in males in the United States). This is typically known as de novo metastatic breast cancer.

Commonly, metastatic breast cancer arises years after an individual has completed treatment for previous or locally advanced breast cancer. This may be known as a distant recurrence.

A diagnosis of stage IV or metastatic breast cancer is not an individual’s fault. The respective individual did nothing to cause this cancer to progress or spread.

The stage IV breast cancers come from the cells of breast cancer that remained in the body after treatment for early breast cancer. The breast cancer cells were always there but could not be detected. For some unknown reason, the cancer cells began to grow again. This process is not well-understood.

The Probability of Metastatic (Stage IV) Breast Cancer:

The probability of metastasis following the treatment of breast cancer varies from individual to individual. It depends on:

  • The biology of the tumor (characteristics of the cancer cells)
  • The stage at the time of the original diagnosis
  • The therapies for the original cancer (trying to prevent breast cancer recurrence)

Metastatic (Stage IV) Breast Cancer Prognosis (Chance of Survival):

New era’s treatments continue to improve the survival for those with metastatic breast cancer. However, survival varies greatly from individual to individual.

About one-third of females diagnosed with metastatic or stage IV breast cancer in the United States live at least 5 years after diagnosis. Some females may live 10 or more years beyond diagnosis.

An oncologist can tell you about your prognosis, but they also don’t know exactly how long your chance of survival would be.

Metastatic Breast Cancer Treatment

As tough as it is to hear, metastatic (stage IV) breast cancer is hard to be cured. Unlike breast cancer that stays in the breast or surrounding lymph nodes, medical therapies can’t get rid of all the cancer that progressed to other organs of the body.

Although, metastatic or stage IV breast cancer can be treated. The goal of treatment is to extend life and maintain quality of life (QoL).

A treatment plan is typically guided by several factors, including:

  • Characteristics of the cancer cells
  • Where the cancer has spread
  • Your signs/symptoms
  • Previous breast cancer treatments
  • Your age, overall health, menopausal status and other medical complications
  • Personal goals and preferences

Drug Therapies for Metastatic (stage IV) Breast Cancer

There are several drug therapies that can be used to treat metastatic (stage IV) breast cancer. Let’s learn about drug therapies that may be part of your treatment plan.

Hormone therapy (endocrine therapy): Progesterone and estrogen are female hormones formed in the body. Some breast cancer cells need progesterone/estrogen to grow.

When progesterone/estrogen attach to special proteins known as hormone receptors, the cancerous cells with these receptors progress.

These (hormone therapy) medicines work by preventing the cancerous cells from getting the estrogen they need to progress. 

Hormone therapies can be addressed as endocrine therapies. This therapy is typically the first treatment for hormone receptor-positive (HR+) metastatic breast cancers.

For those (women), the choice of hormone therapy typically depends on menopausal status and any previous hormone treatment for early breast cancer.

Some hormone therapy medicines are pills and some are administered by injection under the skin (a shot). Most widely used hormone therapy drugs are as follows:

Anastrozole (Arimidex): Anastrozole is supplied under the brand name Arimidex. It is used in the postmenopausal women. This medicinal product is available as a pill. 

Exemestane (Aromasin): Exemestane is supplied under the brand name Aromasin. It is typically for postmenopausal women. It is available as a pill. 
Fulvestrant (Faslodex): Fulvestrant is supplied under the brand-name Faslodex. It is used in the postmenopausal women and available in the form of injection. 
Goserelin (Zoladex): Goserelin is supplied under the brand-name Zoladex. It is for premenopausal women and available in the form of injection. 
Letrozole (Femara): Letrozole is supplied under the brand-name Femara. It is recommended for postmenopausal women. Letrozole (Femara) is available as a pill for oral administration. 
Leuprolide (Lupron): Leuprolide is supplied under the brand-name Lupron. It is recommended for premenopausal women. This medicine is available as an injection form. 
Megestrol acetate (Megace): Megestrol acetate is supplied under the brand-name Megace. It is used for pre- and postmenopausal women. This hormone therapy drug is available in the form of pills for oral administration. 
Tamoxifen (Nolvadex): Tamoxifen is supplied under the brand-name Nolvadex. It is recommended for pre- and postmenopausal women. This medicine is available as pills to be taken by mouth. 
Toremifene (Fareston): Toremifene is supplied under the brand-name Fareston. It is recommended for postmenopausal women. Available in the form of pills, Toremifene should be taken orally. 
 
CDK4/6 inhibitors: CDK4/CDK6 are enzymes essential in cell division. CDK4/CDK6 inhibitors are medicines mainly designed in order to interrupt the progression of cancer cells.
CDK4/CDK6 inhibitors are used along with hormone therapy for treating some hormone receptor-positive (HR+) breast cancers.
The CDK4/CDK6 inhibitors FDA-approved for metastatic or stage IV breast cancer treatment are:
Abemaciclib (Verzenio): Abemaciclib is supplied under the brand-name Verzenio. It is given as a pill by mouth. 
Palbociclib (Ibrance): Palbociclib is supplied under the brand-name Ibrance. This medicine is available in the form of pills for oral administration. 
Ribociclib (Kisqali): Ribociclib is supplied under the brand-name Kisqali. This medicinal product is available as pills for oral administration. 
 
mTOR inhibitors: mammalian targets of rapamycin (mTOR) inhibitors are medicines that may boost the benefit of hormone therapy.
Everolimus (Afinitor): Everolimus is supplied under the brand-name Afinitor. It is an mTOR inhibitor which is used along with hormone therapy for the treatment of some hormone receptor-positive (HR+) metastatic breast cancers.
 
PI3 kinase inhibitors: PI3 kinase is an enzyme important in cell growth. The PIK3CA gene helps control PI3 kinase enzyme activity.
 
Alpelisib (Piqray): Alpelisib is supplied under the brand-name Piqray. It is a PI3 kinase inhibitor which is used along with hormone therapy for the treatment of some hormone receptor-positive (HR+), HER2-negative metastatic breast cancers with a PIK3CA gene mutation that have been previously treated with hormone therapy. The combination of medicines alpelisib and fulvestrant can offer more time before the cancer progress compared to fulvestrant alone 
 
HER2-targeted therapy: HER2 is a kind of protein that’s crucial for cancer cell progression. HER2+ breast cancers have high levels of HER2 on their cancer cell surface. 
A respective pathologist helps determine the status of HER2 by testing tumor tissue eliminated during a biopsy.
Approximately 10 to 20 % of breast cancers are HER2+. The HER2-targeted therapy medicines are used for the treatment of HER2+ breast cancers.
 
Ado-trastuzumab emtansine, T-DM1 (Kadcyla): Ado-trastuzumab emtansine is supplied under the brand-name Kadcyla. It is an IV medicinal product. 
Lapatinib (Tykerb): Lapatinib is supplied under the brand-name Tykerb. It is widely available as a pill for oral administration. 
Margetuximab (Margenza): Margetuximab is supplied under the brand-name Margenza. This medicine is widely available as an injection and given by IV administration. 
Pertuzumab (Perjeta): Pertuzumab is supplied under the brand-name Perjeta. It is an IV drug available in the form of injection. 
Trastuzumab (Herceptin): Trastuzumab is supplied under the brand-name Herceptin. It is an IV medicinal product available in the form of injection. 
Trastuzumab deruxtecan (Enhertu): Trastuzumab deruxtecan is supplied under the brand-name Enhertu. This medicinal product is available as an IV injection. 
Tucatinib (Tukysa): Tucatinib is supplied under the brand-name Tukysa. It is available as 50 mg and 150 mg tablets. Tucatinib along with trastuzumab and capecitabine offers another chance at treating HER2+ metastatic breast cancer. As with all other existing cancer therapies, side effects with tukysa 150 mg tablets are possible.
The most common side effects may include: rash diarrhea, redness, swelling, pain, or blisters on the palms of the hands or soles of the feet, nausea and tiredness. 
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PARP inhibitors: PARP typically is an enzyme involved in the repair of DNA. Some chemotherapy medicinal products damage tumor DNA. PARP inhibitors act in order to block PARP from repairing tumor DNA. This can help the chemo kill the cancerous cells.
Olaparib (Lynparza): Olaparib is poly(ADP-ribose) polymerase (PARP) inhibitor supplied under the brand-name Lynparza. Olaparib is available in the form of pills for oral administration. 
Talazoparib (Talzenna): Talazoparib is a poly(ADP-ribose) polymerase (PARP) inhibitor supplied under the brand-name Talzenna. This medicinal product is available in the form of pills which can be taken orally (by mouth). 
 
Immunotherapy with a checkpoint inhibitor: Checkpoint inhibitors typically are the most widely considered immunotherapy medicines. These medicinal products “take the brakes off” the natural factors that are involved in limiting how the defense system can manage tumor cells.
  • Pembrolizumab (Keytruda): Pembrolizumab is supplied under the brand-name Keytruda. It is a checkpoint inhibitor immunotherapy antibody medicine widely used for the treatment of some metastatic breast cancers.Other immunotherapy medicines for treating metastatic breast cancer are under study.
Trop-2 antibody-drug conjugates: Certain breast cancers have some cells that express the protein Trop-2. Triple negative breast cancers (TNBC) tend to express Trop-2.
Sacituzumab govitecan (Trodelvy): Sacituzumab govitecan is supplied under the brand-name Trodelvy. It is a Trop-2 antibody-drug conjugate, which combines a Trop-2 antibody and the chemo drug SN-38. This combination helps allow the targeted delivery of SN-38 to cancerous cells that express Trop-2.
 
Chemotherapy: For those with metastatic (stage IV) breast cancer, chemotherapy is considered to destroy the cancerous cells that have progressed from the breast to other areas of the body.
Chemotherapy can help reduce the stage IV breast cancer-related signs/symptoms and enhance survival. The chemotherapy is the preferred treatment option for those with metastatic breast cancers that are:
  • HR-negative
  • HR-positive, but no longer respond to hormone therapy
  • HER2+ (along with HER2-targeted therapy)
You’ll be checked every few months in order to see if your cancer is responding to therapy and if the adverse reactions are manageable.
 
In case the first chemo drug (or combination of medicines) stops acting and the cancer starts to progress again, a 2’nd/3’rd medication can be used.
 
Consideration of each chemo drug (or combination of medicines) for stage IV breast cancer is known as a “line” of treatment. For instance, the first chemo medicine used is known as the “first-line” treatment and the second is known as the “second-line” treatment.
 
It’s absolutely common to get multiple lines of chemo regimens (often four or more) over the time-span of treatment for metastatic or stage IV breast cancer. Some most common chemotherapy drugs are as follows:
 
  • Capecitabine (Xeloda)
  • Cisplatin (Platinol)
  • Cyclophosphamide (Cytoxan)
  • Carboplatin (Paraplatin) 
  • Docetaxel (Taxotere)
  • Epirubicin (Ellence)
  • Eribulin (Halaven)
  • Doxorubicin (Adriamycin)
  • 5-Fluorouracil (Adrucil)
  • Ixabepilone (Ixempra)
  • Liposomal doxorubicin (Doxil)
  • Gemcitabine (Gemzar)
  • Methotrexate (Maxtrex)
  • Paclitaxel, albumin bound, also called nab-paclitaxel (Abraxane)
  • Vinorelbine (Navelbine)
  • Paclitaxel (Taxol)
Metastatic stage IV breast cancer can respond to several different medicine therapies. This means the medicines can shrink the tumors.
Although, over time, tumors may stop responding to drugs used for the treatment of metastatic breast cancer.
 
 
Reference: https://www.breastcancer.org/types/metastatic
https://www.nationalbreastcancer.org/metastatic-breast-cancer
https://www.cancercenter.com/cancer-types/breast-cancer/types/rare-breast-cancer-types/metastatic-breast-cancer
 
 
 

 

 
 
Nitin Goswami

Nitin Goswami joined us as an Editor in 2020. He covers all the updates in the field of Pharmaceutical, Business Healthcare, Health News, Medical News, and Pharma News.

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