Systemic Breast Cancer Treatment

Endocrine therapy

The endocrine system is made up of organs and tissues that produce hormones. Hormones are natural chemicals released into the bloodstream.

There are 4 hormones that might be targeted in endocrine therapy:

  • Estrogen is made mainly by the ovaries
  • Progesterone is made mainly by the ovaries
  • Luteinizing hormone-releasing hormone (LHRH) is made by a part of the brain called the hypothalamus. It tells the ovaries to make estrogen and progesterone.
  • Androgen is made by the adrenal glands, testicles, and

Hormones can cause breast cancer to grow. Endocrine therapy will stop your body from making hormones or it will block what

hormones do in the body. This can slow tumor growth or shrink the tumor for a period of time. Endocrine therapy can be local (surgery or ablation) or systemic (drug therapy). It is sometimes called hormone therapy. It is not the same as hormone replacement therapy used for menopause. The goal of endocrine therapy is to reduce the amount of estrogen or progesterone in your body.

There is one type of surgical endocrine therapy that is used for premenopausal women:

  • Bilateral oophorectomy is surgery to remove both ovaries

There are 5 main types of endocrine therapy:

  • Ovarian ablation permanently stops the ovaries from making hormones. Ablation uses extreme hot or cold to stop ovaries from
  • Ovarian suppression temporarily stops the ovaries from making hormones. It is achieved with drugs called LHRH agonists. These drugs stop LHRH from being made, which stops the ovaries from making hormones. LHRH agonists include goserelin (Zoladex®) and leuprolide (Lupron Depot®).
  • Aromatase inhibitors stop a hormone called androgen from changing into estrogen by an enzyme called aromatase. They do not affect estrogen made by the ovaries. Non-steroidal aromatase inhibitors include anastrozole (Arimidex®) and letrozole (Femara®). Exemestane (Aromasin®) is a steroidal aromatase inhibitor.
  • Anti-estrogens prevent hormones from binding to receptors. Selective estrogen receptor modulators (SERMs) block estrogen from attaching to hormone receptors. They include tamoxifen and toremifene (Fareston®). Selective estrogen receptor degraders (SERDs) block and destroy estrogen receptors. Fulvestrant (Faslodex®) is a SERD.
  • Hormones may treat breast cancer when taken in high doses. It is not known how hormones stop breast cancer from growing. They include ethinyl estradiol, fluoxymesterone, and megestrol acetate.

Those who want to have children in the future should be referred to a fertility specialist before starting chemotherapy and/or endocrine therapy to discuss the options.


Options for endocrine therapy are partly  based on if you started or are in menopause. In menopause, the ovaries stop producing hormones and menstrual periods stop. After menopause, estrogen and progesterone levels continue to stay low.

When menstrual periods stop for 12 months or more, it is called postmenopause. If you don’t get periods, a test using a blood sample may be needed to confirm your status. If you have menstrual periods, you are in premenopause.


In premenopause, your ovaries are the main source of estrogen and progesterone. Ovarian ablation or suppression help reduce hormone levels. For premenopause, ovarian ablation or suppression will be used with systemic therapy and/or an aromatase inhibitor.


In postmenopause, your adrenal glands, liver, and body fat make small amounts of estrogen. Often in postmenopause, an aromatase inhibitor and a targeted therapy are used together.

HER2-targeted therapy

HER2 is a protein involved in normal cell growth. There might be higher amounts of HER2 in your breast cancer. If this is the case, it is called HER2-positive breast cancer (HER2+). HER2-targeted therapy is drug therapy that treats HER2+ breast cancer.

HER2-targeted therapies include:

  • Pertuzumab (Perjeta®)
  • Trastuzumab (Herceptin®)
  • Trastuzumab substitutes such as Kanjinti™, Ogivri®, Herzuma®, Ontruzant®, and Trazimera™
  • Ado-trastuzumab emtansine (T-DM1) (Kadcyla®)
  • Fam-trastuzumab deruxtecan-nxki (Enhertu®)
  • Lapatinib (Tykerb®)
  • Neratinib (Nerlynx®)

Most often, HER2-targeted therapy is given with chemotherapy. However, it might be used alone or in combination with endocrine therapy.

HER2-targeted therapies include:

  • HER2 antibodies prevent growth signals from HER2 from outside the cell. They also increase the attack of immune cells on cancer cells. These drugs include trastuzumab (Herceptin®) and pertuzumab (Perjeta®).
  • HER2 inhibitors stop growth signals from HER2 from within the cell. Lapatinib (Tykerb®) and neratinib (Nerlynx®) are examples of these
  • HER2 conjugates deliver cell-specific chemotherapy. They attach to HER2s then enter the cell. Once inside, chemotherapy is released. Ado-trastuzumab emtansine (Kadcyla®) and fam-trastuzumab deruxtecan-nxki (Enhertu®) are included in this class.


Chemotherapy is a type of drug therapy used to treat cancer. Chemotherapy kills fast-growing cells throughout the body, including cancer  cells and normal cells. All chemotherapy drugs affect the information inside genes called DNA (deoxyribonucleic acid). Genes tell cancer cells how and when to grow and divide. Chemotherapy disrupts the life cycle of cancer cells.

There are different types of chemotherapy used to treat invasive breast cancer:

  • Alkylating agents damage DNA by adding a chemical to it. This group of drugs includes Platinum-based alkylating agents contain a heavy metal that prevents cancer cells from dividing. These drugs include carboplatin and cisplatin (Platinol®).
  • Anthracyclines damage and disrupt the making of DNA causing cell death of both cancerous and non-cancerous cells. These drugs include doxorubicin, doxorubicin liposomal injection (Doxil®), and epirubicin (Ellence®).
  • Antimetabolites prevent the “building blocks” of DNA from being used. These drugs include capecitabine (Xeloda®), fluorouracil, gemcitabine (Gemzar®), and methotrexate.
  • Microtubule inhibitors stop a cell from dividing into two cells. These drugs include docetaxel (Taxotere®), eribulin (Halaven™), ixabepilone (Ixempra® Kit), paclitaxel (Taxol®, Abraxane®), and vinorelbine (Navelbine®). Docetaxel, paclitaxel, and albumin-bound paclitaxel are also called taxanes.

More than one drug may be used to treat invasive breast cancer. When only one drug is used, it’s called a single agent. A combination regimen is the use of two or more chemotherapy drugs.

Some chemotherapy drugs are liquids that are infused into a vein or injected under the skin with a needle. Other chemotherapy drugs may be given as a pill that is swallowed.

Most chemotherapy is given in cycles of treatment days followed by days of rest. This allows the body to recover before the next cycle. Cycles vary in length depending on which drugs are used. The number of treatment days per cycle and the total number of cycles given also varies.

Birth control during treatment

If you get pregnant during chemotherapy, radiation therapy, endocrine therapy, or systemic therapy, serious birth defects can occur. If you had menstrual periods before starting chemotherapy, use birth control without hormones. Condoms are an option. “The pill” is not. Speak to your doctor about preventing pregnancy while being treated for breast cancer.

Those who want to have children in the future should be referred to a fertility specialist before starting chemotherapy and/or endocrine therapy to discuss the options.


Bone-targeted therapy

Medicines that target the bones may be given to help relieve bone pain or reduce the risk of bone problems. Some medicines work by slowing or stopping bone breakdown, while others help increase bone thickness.

When breast cancer spreads to distant sites,  it may metastasize in your bones. This puts your bones at risk for injury and disease. Such problems include bone loss (osteoporosis), fractures, bone pain, and squeezing (compression) of the spinal cord. Some treatments for breast cancer, like endocrine therapy, can cause bone loss, which put you at an increased risk for fractures.

There are 3 drugs used to prevent bone loss and fractures:

  • Zoledronic acid (Zometa®)
  • Pamidronate (Aredia®)
  • Denosumab (Prolia®)

There are 3 drugs used to treat bone metastases:

  • Zoledronic acid (Zometa®)
  • Pamidronate (Aredia®)
  • Denosumab (Xgeva®)

You will be screened for osteoporosis using a bone mineral density test. This measures how much calcium and other minerals are in your bones. It is also called a dual-energy x-ray absorptiometry (DEXA) scan and is painless. Bone mineral density tests look for osteoporosis and help predict your risk for bone fractures.

A baseline DEXA scan is recommended before starting endocrine therapy.

Zoledronic acid, pamidronate, and denosumab

Denosumab, pamidronate, and zoledronic acid are used to prevent bone loss (osteoporosis) and fractures caused by endocrine therapy.

Denosumab and zoledronic acid are also used in those with metastatic breast cancer who have bone metastases to help prevent fractures or spinal cord compression. You might have blood tests to monitor kidney function, calcium levels, and magnesium levels. A calcium and vitamin D supplement will be recommended by your doctor.

Let your dentist know if you are taking any of these medicines. Also, ask your doctor how these medicines might affect your teeth and jaw. Osteonecrosis, or bone tissue death of the jaw, is a rare but serious side effect. Tell your doctor about any planned trips to the dentist. It will be important to take care of your teeth and to see a dentist before starting treatment with any of these drugs.


Other targeted therapies

CDK4/6 inhibitors

Cyclin-dependent kinase (CDK) is a cell protein that helps cells grow and divide. For hormone-positive, HER2- cancer, taking a CDK4/6 inhibitor with endocrine therapy may help control cancer longer. With all CDK4/6 regimens, premenopausal women must also receive ovarian ablation or suppression.

mTOR inhibitors

mTOR is a cell protein that helps cells grow and divide. Endocrine therapy may stop working if mTOR becomes overactive. mTOR inhibitors are used to get endocrine therapy working again.

Everolimus (Afinitor®) is an mTOR inhibitor. Most often, it is taken with exemestane. For some, it may be taken with fulvestrant or tamoxifen.

PARP inhibitors

Cancer cells often become damaged. PARP is a cell protein that repairs cancer cells and allows them to survive. Blocking PARP can cause cancer cells to die. Olaparib (Lynparza®) and talazoparib (Talzenna®) are PARP inhibitors. You must have the BRCA1 or BRCA2 mutation and your breast cancer must be HER2- for PARP inhibitors to be effective.

PIK3CA inhibitor

The PIK3CA gene is one of the most frequently mutated genes in breast cancers. A mutation in this gene can lead to increased growth of cancer cells and resistance to various treatments.



Immunotherapy is a type of systemic treatment that increases the activity of your immune system. By doing so, it improves your body’s ability to find and destroy cancer cells.

Immunotherapy can be given alone or with other types of treatment.



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