Targeted therapy

Targeted therapies are treatments that target specific proteins or markers on or within cancer cells that help the cells to grow. Targeted therapies may be used alone or with other targeted therapies, hormonal therapies, or chemotherapy medicines. Your doctor may also call these treatments tailored or biologic therapies.

Targeted therapies look for a specific feature of a cancer cell, attach to it and destroy it. Only cancers with that feature will respond to the therapy. Some examples are:

• If the breast cancer tests positive for the HER2 receptor, you may be able to receive a targeted therapy that only targets HER2-positive cells
• Medicines that block the growth of blood vessels that most tumors need to grow
• Therapies that work like antibodies made by the immune system

Unlike chemotherapy, targeted therapies only kill only cells with that particular target, meaning fewer effects on healthy cells. For this reason, targeted therapies by themselves have far fewer side effects than chemotherapy medicines. But each targeted therapy has unique side effects that you should discuss with your doctor.

Hormonal therapies targeting the estrogen receptor and the progesterone receptors are the earliest examples of targeted therapy. Some targeted therapies can be used along with hormonal therapy to make hormonal therapy more effective at killing the cancer.

There are many kinds of targeted therapy, and researchers will likely find others as they learn more about what makes certain cancers grow. Targeted treatments are helping scientists and doctors personalize treatment plans so they can better treat different types of cancer.

Many forms of targeted therapy are being tested in clinical trials. They are given intravenously (by vein) or by mouth as a pill. Some treatments have already been approved by the FDA, but others are only available in clinical trials.

You will need tests to know whether the cancer will respond to targeted therapy. Sometimes, you may be offered a targeted therapy only in specific situations. You may be offered targeted therapy if you have:

• early-stage HER2-positive breast cancer
• metastatic HER2-positive breast cancer
• metastatic hormone receptor-positive, HER2-negative breast cancer, and you already went through menopause

If you are interested in other targeted therapies, ask your doctor about a clinical trial.

Neoadjuvant vs. adjuvant targeted therapy

Targeted therapy for breast cancer can be given either:

• before surgery, which is called neoadjuvant therapy, or
• after surgery, which is called adjuvant therapy.

Neoadjuvant therapy

Neoadjuvant therapy is full-body, or systemic, treatment given as a first step to shrink tumors or slow cancer spread before surgery.

Neoadjuvant therapy is more commonly used for breast cancer that is locally advanced, or has traveled outside the breast to other nearby organs or tissues such as lymph nodes, skin or chest wall.

If you can have neoadjuvant therapy, you will have a needle biopsy to learn more about the type of breast cancer you have and decide which therapy will benefit you most.

You may be able to get neoadjuvant therapy if you have a HER2-positive tumor that is too large to remove with lumpectomy. The goal of neoadjuvant therapy would be to shrink the tumor to a size that could allow you to have lumpectomy instead of mastectomy.

Neoadjuvant therapy may change the timing of your treatment or allow you to avoid mastectomy, but studies show it does not lengthen life, or survival, over receiving therapy after surgery.

Targeted medicines that may be used as neoadjuvant therapy for HER2-positive breast cancer are:

• trastuzumab (Herceptin): This medicine is given with chemotherapy. If you get trastuzumab before surgery, you will likely get it after surgery to complete your treatment.
• pertuzumab (Perjeta): Pertuzumab is given with trastuzumab and chemotherapy before surgery. Afterward, you would continue taking trastuzumab to finish your treatment.

After neoadjuvant targeted therapy, you may have tests, such as a mammogram or MRI, to see how the cancer responded to therapy. Then, surgery will be scheduled.

After your surgery, a pathologist will check the tissue that was removed for any signs of cancer. In some cases, there may be a complete response to therapy, meaning the doctor can find no evidence of remaining disease, or NED. When cancer completely goes away, it is linked to better overall outcomes. But you will still need to finish your treatment plan to lessen your risk for cancer return.

Adjuvant therapy

Adjuvant therapy is treatment given after surgery to lower the risk of the breast cancer coming back and increase the chance of long-term survival. The goal is to kill any cancer cells that may have traveled away from the breast or lymph nodes. If you are at higher risk of recurrence, you are more likely to need adjuvant therapy.

The targeted therapy trastuzumab is given with chemotherapy as a standard adjuvant treatment for early-stage, HER2-positive breast cancer. Trastuzumab lowers the risk for distant recurrence.

Targeted therapy for metastatic breast cancer

A number of other targeted therapy medicines are approved only for metastatic breast cancer. These are:

• Antibody-drug conjugates:
  • Ado-trastuzumab emtansine (Kadcyla), which treats HER2-positive metastatic breast cancer
  • Sacituzumab govitecan (Trodelvy), which treats triple-negative metastatic breast cancer and hormone receptor-positive, HER2-negative metastatic breast cancer
  • Trastuzumab deruxtecan (Enhertu), which treats HER2-positive metastatic breast cancer

• Cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors that treat hormone receptor-positive, HER2-negative metastatic breast cancer:
  • Palbociclib (Ibrance)
  • Ribociclib (Kisqali)

• Alpelisib (Piqray), a PI3K inhibitor, which treats hormone receptor-positive metastatic breast cancer
• Everolimus (Afinitor), an mTOR inhibitor, which treats hormone receptor-positive, HER2-negative metastatic breast cancer
• Lapatinib (Tykerb), a dual tyrosine kinase inhibitor, which treats HER2-positive metastatic breast cancer
• Margetuximab (Margenza), a monoclonal antibody, which treats HER2-positive metastatic breast cancer
• Talazoparib (Talzenna), a PARP inhibitor, which treats hormone receptor-positive, HER2-negative metastatic breast cancer in people who test positive for an inherited BRCA gene mutation
• Tucatinib (Tukysa), a tyrosine kinase inhibitor, which treats HER2-positive metastatic breast cancer

Bevacizumab (Avastin) and PARP inhibitors such as BSI-201 and ABT-888 are not FDA-approved but may be available to you through clinical trials if you have stage IV breast cancer.

Many forms of neoadjuvant and adjuvant targeted therapy are being tested in clinical trials. Talk with your doctors about open clinical trials that may be available to you. You can also visit our section on Clinical trials and research studies for more information.