Targeted therapy for breast cancer

Targeted therapies are a type of treatment used to fight certain types of breast cancers. Specifically, targeted therapies zero in on proteins that control how cancer grows, divides and spreads in the body. It’s also a form of “precision medicine.”

These treatments sometimes are used in conjunction with cancer treatments like chemotherapy and radiation therapy for breast cancer because cancer cells can become resistant to targeted therapies over time.

When are targeted therapies used?

Targeted therapies have greatly improved outcomes for some patients with hormone receptor-positive and HER2-positive cancers. A HER2-positive breast cancer is one that has higher levels of the HER2 protein on the surface of the breast cancer cells. This causes the cancer cells to grow and spread faster.

Experts recommend that women who have invasive breast cancer get tested for HER2 using tissue from a biopsy or surgery with one of these two tests:

• Immunohistochemical stains (IHC)
• Fluorescent in situ hybridization (FISH)

It’s also possible for cancer to be hormone receptor positive. Both normal breast cells and some breast cancer cells have receptors. Estrogen and progesterone are hormones that can attach to receptors—or proteins—located in or on cells. This can cause cancer to grow.

Hormone receptor-positive cancers typically grow more slowly and may have better short-term outcomes. These cancers sometimes return many years later.

An immunohistochemistry test is used to determine whether cancer cells have these hormone receptors. A positive means that at least 1 percent of the patient’s cells have these estrogen or progesterone receptors.

Targeted therapies might also be used for:

• Triple-positive cancers, which are estrogen receptor-positive and progesterone receptor-positive, as well as HER2-positive
• Triple-negative cancers, which are negative in hormone receptors and also don’t make too much of the HER2 protein
• Cancer in people who have the BRCA1 or BRCA2 genetic mutation

Particularly when breast cancer is detected early, targeted therapy treatments may help destroy the cancer. When combined with chemotherapy, targeted therapy may also have an impact on lowering the risk of the cancer returning.

Targeted therapy drugs by breast cancer type

HER2-positive breast cancers are more likely to respond to drugs that target the protein. Some cancers are both HER2-positive and ER- and PR-positive. Those would typically be treated with a combination of drugs designed to target all those types of cancer.

HER2-positive cancer treatments include:

• Monoclonal antibodies
• Antibody-drug conjugates
• Kinase inhibitors

Monoclonal antibodies include trastuzumab, which:

• Is also known as Herceptin^®, Ogivri^®, Herzuma^®, Ontruzant^®, Trazimera™, Kanjinti™ and Herceptin Hylecta™
• Is an intravenous (IV) drug or injection delivered over a few minutes, depending on the type
• Can be used on its own or in conjunction with chemotherapy for breast cancer, to slow or stop the growth of the cancer cells
• Is typically given for six months to a year, at three-week intervals, but sometimes longer
• Can also be used to treat cancer that has metastasized, or spread to other parts of the body

Another monoclonal antibody is pertuzumab (Perjeta^®), which:

• Is an intravenous drug
• Can be given with trastuzumab and chemotherapy

These treatments can be used in both early and advanced breast cancer.

A third monoclonal antibody option is margetuximab (Margenza™), which:

• Is an intravenous drug
• Is used after two other targeted therapies have been used for metastatic breast cancer
• Can be used with chemotherapy for advanced breast cancer

Sometimes people need a combination of these targeted therapies for HER2-positive cancers. The U.S. Food and Drug Administration (FDA) approved the drug, Phesgo™, a combination of two medications, trastuzumab and pertuzumab, delivered in a subcutaneous form. The drug includes an additional medicine, hyaluronidase, whose side effects may include nasal congestion and drainage.

For hormone receptor-positive cancers, a variety of targeted treatment options exist.

Some drugs block what are known as CDKs, or cyclin-dependent kinases. These CDK4 and CDK6 inhibitors are designed to slow cancer growth in women with advanced hormone receptor-positive cancer. Some are given in combination with other medications, depending on the patient’s menstrual or menopausal status. They are delivered in pill form.

Other treatment options include mTor inhibitor and a P13K inhibitor.

• mTor inhibitor: Everolimus (Afinitor^®) is used in many patients who are post-menopausal and have advanced cancer that is ER- or PR-positive. It is designed to block a protein that helps cells grow and divide. It may increase the effectiveness of hormone therapy drugs and stop tumors from developing new blood vessels.
• P13K inhibitor: Alpelisib (Piqray^®) may help stop cancer cells from growing and is taken as a pill once daily.

Women who have a mutation of the BRCA1 or BRCA2 gene may consider targeted therapy that blocks+ the proteins helping to keep cancerous cells intact.

These PARP inhibitors block PARP proteins and cause tumor cells to die. These drugs are taken in pill form twice daily. They may be recommended for women who have cancer that has metastasized and who have already had chemotherapy.

Triple-negative breast cancer is when your cancer does not make too much of the HER2 protein and it doesn’t have estrogen or progesterone receptors.

A monoclonal antibody targeted therapy used in this type of cancer is sacituzumab govitecan (Trodelvy^®):

• Is an intravenous treatment
• Is paired with chemotherapy and delivers chemo to the cells
• Can also be used on its own to treat metastasized cancer after two chemotherapy treatments have been tried

Side effects

Targeted therapies may cause side effects that can range in severity and duration, depending on the specific treatment plan you’re on.

Some are mild, like rash and skin changes, while others may be more severe. Since the side effects vary so widely by the type of targeted therapy taken, it's important to speak with your doctor about the side effects you should expect with your treatment plan, and what you can do to manage them throughout your regimen.