Systemic Therapies

Anti-Estrogen Therapies   |    Anti-HER2 Therapies   |    Chemotherapy

Systemic treatments have improved immensely over the last two decades. Treatment options for patients who have developed metastatic breast cancer have more than doubled since 1980, and the lives of most patients with metastatic disease are improved greatly. However, patients with metastatic breast cancer are rarely, if ever, cured; currently available therapies can prolong life but almost never make the cancer go away completely.

Nearly 50 years ago, clinical scientists wondered whether it might be more effective to treat all patients with systemic therapies before their cancer grew into detectable metastases, rather than waiting for these to occur. Such a strategy is called "adjuvant" systemic therapy. Many prospective randomized clinical trials have consistently shown that adjuvant therapy is much more effective in improving survival than delaying therapy until, or if, a patient develops metastases.

Anti-Estrogen Therapies

Estrogen can promote the development of some cancers in the breast. Therefore, medications to block estrogen are often used to treat these cancers. The most widely used anti-estrogen therapy is tamoxifen, a drug that blocks the effects of the hormone estrogen in the breast. As adjuvant therapy, tamoxifen helps prevent the original breast cancer from returning. It also helps prevent the development of new cancers in the other breast. As treatment for metastatic breast cancer, the drug slows or stops the growth of cancer cells that are present in the body.

Another type of anti-estrogen drug is called an aromatase inhibitor (AI), which is a drug that prevents the formation of estradiol. Aromatase inhibitors are used as a type of anti-estrogen therapy for postmenopausal women who have hormone-dependent breast cancer. They can also be used to treat premenopausal women as long as they also either remove their ovaries or stop their function by medical treatment.

There are three aromatase inhibitors on the market: anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). Currently, none of these appears to be superior to the others with respect to activity or side effects, so a patient might receive any one of the three.

Anti-HER2 Therapies

HER2 is a protein that sits on the surface of a cancer cell and helps control the signals from outside the cell to the nucleus. An anti-HER2 therapy helps to keep the HER2 protein from working, thereby slowing or stopping the growth of cancer cells.

Multiple anti-HER2 herapies have been developed. The first to be developed was an antibody called trastuzumab, or Herceptin. Trastuzumab binds to HER2 and keeps it from working within the cell. Trastuzumab does not seem to work in cells that do not make HER2. Multiple additional intravenous medications have also been developed including antibodies (pertuzumab [Perjeta]) and drugs that are a combination of antibodies and chemotherapies (ado-trastuzumab emtansine [Kadcyla], trastuzumab deruxtecan [Enhertu]). Some of these medications are used in the adjuvant setting to help prevent the originally breast cancer from returning. All are used as treatment for metastatic breast cancer, the drug slows or stops the growth of cancer cells that are present in the body.

Other anti-HER2 drugs that patients take orally have been developed are lapatinib (Tykerb), neratinib (Nerlynx), and tucatinib (Tukysa). They acts by entering a cancer cell and binding to the part of the HER2 protein that lies beneath the surface of the cell. Neratinib is used in the adjuvant setting to help prevent the originally breast cancer from returning. All are used as treatment for metastatic breast cancer, the drug slows or stops the growth of cancer cells that are present in the body.

Chemotherapy

Chemotherapy is treatment with drugs. Chemotherapy works in many ways, but basically it targets cells that are dividing rapidly. Therefore it is not as specific as anti-estrogen or anti-HER2 therapy and has more side effects. Large randomized trials have demonstrated that overall chemotherapy reduces the chances of distant metastases by approximately 30%.

The decision to use chemotherapy or not is based on the risk of cancer showing up in areas of the body separate from the breast, called distant metastases. It is not given to reduce the risk of cancer returning in the breast, and therefore undergoing mastectomy instead of lumpectomy does not alter the potential need for treatment with chemotherapy. Thus, the surgical therapy decision should not be made in hopes of avoiding chemotherapy.

There are many drugs that are effective against breast cancer cells. These drugs are frequently combined into regimens. Treatments may be given every day, every week or every month. The treatment period is followed by a period of rest, with no chemotherapy, to give your body a chance to build healthy new cells.

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