Systemic Therapy

Systemic Therapy

Surgery and radiation treat breast cancer in the breast and axilla. Systemic therapy treats breast cancer cells that can not be treated by surgery or radiation, as well as treating breast cancer in the breast and axilla. The goal of systemic therapy, which gives medication via the bloodstream, is to treat the whole body.

Systemic therapy is most often given in the “adjuvant” setting (in other words, after surgery has been performed) to decrease the risk of the cancer returning. Your doctor will decide whether you need adjuvant systemic therapy and the type of therapy needed based on the size of the tumor, whether or not it has spread to lymph nodes, the tumor marker profile of your cancer (your cancer’s biology), and possibly genomic testing of your tumor (your cancer’s DNA).

Systemic therapy can also be given “neoadjuvantly,” meaning before surgery. Neoadjuvant therapy is recommended if a cancer is too large to be removed by surgery, in hopes of shrinking the cancer so that it can be surgically removed or, in some cases, to enable a lumpectomy to be performed instead of a mastectomy.

Systemic therapy is also given to patients whose cancer has recurred or spread to other organs. Once a breast cancer has metastasized outside of the breast and axilla, surgery plays a very small role in treatment and systemic therapy is used to kill or control the growth of the cancer.

Three different types of systemic therapies are used to treat breast cancer:

  • Chemotherapy
  • Hormone therapy
  • Targeted therapy


Chemotherapy is considered a systemic therapy in the treatment of breast cancer. It is most often given as an adjuvant therapy (after surgery), but can also be given before surgery (neoadjuvantly). Chemotherapy is also often used to treat breast cancer that has recurred or spread (metastasized).

Chemotherapy is usually prescribed by a medical oncologist. It is most often given intravenously through a port-a-catheter, but some chemotherapy drugs come in pill form.

Usually chemotherapy is given in cycles with time to recover between treatments. The type of chemotherapy drug your medical oncologist prescribes determines how long each cycle is. Some drugs are given only once every 2 to 3 weeks, while others are given daily for a week to 2 weeks.

Chemotherapy Drugs

Many different chemotherapy drugs are used to treat patients with breast cancer. The following are the most common chemotherapy drugs that your doctor may prescribe:

Chemical Name










Brand Name




(Adriamycin, Doxil)


(5-FU, Adrucil)

(Amethopterin, Maxtrex, Mexate, Folex)




Other chemotherapy drugs used to treat breast cancer include:

Chemical Name











Brand Name


(Cerubidine, DaunoXome)







(Oncovin, Vincrex, Vincasar)



In many instances these chemotherapy drugs are given as combinations. The most common combinations of chemotherapy drugs used to treat breast cancer are:


Adriamycin and Cytoxan


Adriamycin, Cytoxan, and either Taxol or Taxotere


Adriamycin and Taxotere



Cytoxan, Adriamycin, and fluorouracil 

(CAF and FAC use the same chemotherapy drugs, but in different doses and cycles)


Cytoxan, Ellence, and fluorouracil


Cytoxan, Methotrexate, and fluorouracil


Gemzar, Ellence, and Taxol


Taxotere, Adriamycin, and Cytoxan

Your medical oncologist will discuss the different chemotherapy drugs with you. The type of chemotherapy drugs recommended to you will depend on the type of breast cancer you have, the stage of the cancer, and the other medical problems you may have. Together you and your medical oncologist will decide the best treatment regimen for your type of breast cancer. 

Side Effects

Chemotherapy drugs work by killing cells that are dividing quickly, but they can not tell the difference between cancer cells and other cells in your body that are also dividing quickly. Because chemotherapy drugs affect the hair follicles, bone marrow, intestinal lining, and cells of your mouth, they can cause the following common side effects:
  • Hair loss
  • Fatigue
  • Nausea and vomiting
  • Immunosuppression (increased susceptibility to infection)
  • Easy bruising
  • Mouth sores
Other side effects of chemotherapy drugs include:
  • Neuropathy, which is numbness and/or tingling of fingers and/or toes (nerve damage)
  • Decreased mental function, which usually presents as forgetfulness (chemo brain)
  • Osteoporosis
  • Damage to other organs, such as the heart
  • Infertility
  • Premature menopause

Most of these side effects are temporary and will resolve shortly after chemotherapy is stopped. Other side effects may take a few months to resolve, and a few side effects, such as heart damage, infertility, and premature menopause, may be permanent. Your doctor can offer you different treatments to minimize these side effects; therefore, it is very important to tell your doctor of any new symptoms you are experiencing.

Hormone Therapy (Hormone-Blocking Therapy)

Hormone therapy is considered a systemic therapy in the treatment of breast cancer. It is most often given as an adjuvant therapy after surgery to decrease the risk of the cancer coming back, but can also be given in the neoadjuvant setting to decrease the size of the cancer in the breast prior to surgery. It is also used to treat breast cancer that has recurred or spread.

Hormone therapy is recommended for patients whose tumors are positive for either the estrogen (ER) or progesterone (PR) receptors. In patients with hormone-positive tumors, these hormones naturally made by the body cause the cancer to grow. The goal of hormone therapy is to either block the production of hormones or to block the hormones from working.

Most hormone therapy drugs are in pill form and are taken daily.

Drugs That Block Hormones

Selective Estrogen Receptor Modulators (SERMs)

Tamoxifen is the most well known of the SERMs prescribed today. It acts by blocking estrogen from attaching to the estrogen receptor on cancer cells. It is a selective modulator because on other cells, such as in the uterus, it works by increasing estrogen.

Raloxifene (Evista) and toremifene (Fareston) are other types of SERMs that may be prescribed by your doctor.

The most common side effects of the SERMs are:
  • Hot flashes
  • Vaginal dryness
  • Night sweats
  • Mood swings
  • Fatigue
More serious side effects of the SERMs include:
  • Blood clots (especially in women who smoke)
  • Uterine cancer (Tamoxifen only)
  • Cataracts
  • Stroke

Estrogen Receptor Downregulators (ERDs)

Fulvestrant (Faslodex) is the only ERD currently prescribed for the treatment of breast cancer. Fulvestrant works like a SERM in the breast tissue. It is given to patients who have gone through menopause. Unlike other hormonal therapy drugs, fulvestrant is a liquid given once a month as an injection into a muscle.

The most common side effects of fulvestrant are:
  • Pain at the injection site
  • Nausea/vomiting
  • Diarrhea or constipation
  • Sore throat
  • Back pain
  • Headaches
  • Hot flashes

Drugs That Lower Hormone Levels

Medications that stop the body from making estrogen are prescribed to women who have gone through menopause. These drugs are called aromatase inhibitors (AIs) and are given in pill form.

The most common AIs are:
  • Anastrazole (Arimidex)
  • Exemestane (Aromasin)
  • Letrozole (Femara)
The most common side effects of the AIs are:
  • Joint pain
  • Hot flashes
  • Vaginal dryness
  • Night sweats
  • Osteoporosis

If you are going to be on an aromatase inhibitor, it is very important to have a bone density test. If your bone density is low, you can be prescribed medication to help strengthen your bones while you are on the AI.

Ovarian Suppression

In premenopausal women, most of the estrogen in the body is produced by the ovaries. Ovarian suppression can be accomplished by surgery or with medications. 


Oophorectomy is the surgical removal of the ovaries. This is a permanent removal of the ovaries and will put a patient into menopause. Because estrogen is made in small amounts elsewhere in the body, you may still be prescribed tamoxifen or an AI to block these hormones.

Ovarian Suppressive Medications

Medications to suppress the ovaries from making estrogen are also available. These medications temporarily shut down the hormone production of the ovaries, meaning that when the medication is stopped the ovaries will start to make hormones again.

The 2 most common ovarian suppressive medications are goserelin (Zoladex) and leuprolide (Lupron). They are both luteinizing hormone-releasing hormone (LHRH) agonists and work by telling the ovaries to stop making hormones. They are also given as injections, usually monthly.

The most common side effects of these medications are:
  • Pain at the injection site
  • Hot flashes
  • Nausea
  • Weight gain
  • Bone pain

Targeted Therapy

Targeted drug therapies for breast cancer are also systemic treatments that attack a specific abnormality on the breast cancer cells. Targeted drug therapies, similar to chemotherapy and hormone therapy, can be given before surgery (neoadjuvantly), after surgery (adjuvantly), or to treat recurrences or metastases to other organs. Unlike chemotherapy drugs, targeted therapies usually do not attack normal cells in the body.

HER2 Therapies

HER2, also known as human epidermal growth factor receptor 2, is a protein that when overexpressed on cancer cells promotes cancer cell growth. HER2-positive cancers tend to be more aggressive, but the treatments targeting HER2 that are now available are so effective that the prognosis for patients with these tumors is very good.

Trastuzumab (Herceptin)

Trastuzumab is an antibody against the HER2 protein. It is usually given to patients as an infusion. In some situations it is given in combination with chemotherapy drugs. It is usually given every 3 weeks for a full year when treating a patient around the time of surgery. For patients who develop HER2-positive metastases, it can be given indefinitely.

Pertuzumab (Perjeta)

Pertuzumab is a newer antibody against the HER2 protein. It is given in combination with trastuzumab and a chemotherapy drug for patients undergoing neoadjuvant treatment prior to surgery. Pertuzumab has also been approved for the treatment of metastatic HER2-positive breast cancers. Similar to trastuzumab, it is given intravenously every 3 weeks.

The other agents against HER2 are lapatinib (Tykerb), which is given in pill form, and ado-trastuzumab emtansine (Kadcyla), which is given intravenously.

Some of the side effects of these medications are:

  • Nausea
  • Fever
  • Muscle aches
  • Chills
  • Diarrhea
  • Hair loss
  • Neuropathy
  • Hand-foot syndrome
  • Congestive heart failure

Although the risk of congestive heart failure is low, if you are placed on these medications your heart will be monitored closely with either an echocardiogram or MUGA scan before treatment and every few months while on the medications.

mTOR Inhibitors

Everolimus (Afinitor)

Everolimus is a drug that blocks the mTOR protein on cancer cells. It is used along with exemestane (Aromasin) to treat hormone-positive cancers that have grown while on anastrazole or letrozole.  Everolimus is a pill that is taken every day.

The most common side effects of everolimus are:
  • Fatigue
  • Nausea
  • Diarrhea
  • Cough
  • Mouth sores
  • Increased risk of infection

Kinase Inhibitors

Palbociclib (Ibrance)

Palbociclib (Ibrance) is a drug that blocks 2 proteins in cells: cyclin-dependent kinase (CDK) 4 and 6. It is prescribed with an aromatase inhibitor to treat patients with advanced hormone-positive cancers. Palbociclib is given as a pill that is taken daily for 3 weeks with a week off before starting the cycle again.

The most common side effects of palbociclib are:
  • Fatigue
  • Nausea
  • Diarrhea
  • Hair loss
  • Mouth sores
  • Anemia