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Targeted drugs treat cancer by targeting specific features, changes, mutations, or substances in or on cancer cells. They are designed to stop cancer cells from growing and spreading while limiting damage to normal, healthy cells.

Many targeted drugs have been approved for use in treating breast cancer. As with other medicines, using these drugs in men is often based largely on how well they work in women.

Targeted therapy for HER2-positive breast cancer

In HER2-positive breast cancer, the cancer cells have too much of a protein called HER2 that helps the cells grow. These cancers tend to grow and spread more aggressively.

Several types of drugs have been developed to target the HER2 protein.

Monoclonal antibodies

Monoclonal antibodies are lab-made versions of immune system proteins (antibodies) that are designed to attach to a specific target. In this case, they attach to the HER2 protein on cancer cells, which can help stop the cells from growing.

Trastuzumab (Herceptin and other brand names) can be used to treat both early-stage and advanced breast cancer. This drug is often given with chemo, but it might also be used alone (especially if chemo alone has already been tried).

When started before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy) to treat early breast cancer, this drug is usually given for 6 months to a year. For advanced breast cancer, treatment is often given for as long as the drug is helpful.

It can be given as an infusion into a vein (IV) or as a subcutaneous (under the skin) injection. The injected form is called trastuzumab and hyaluronidase injection (Herceptin Hylecta).

Pertuzumab (Perjeta) can be given with trastuzumab and chemo, either before or after surgery to treat early-stage breast cancer, or to treat advanced breast cancer. It’s given as an infusion into a vein (IV).

Trastuzumab, pertuzumab, and hyaluronidase (Phesgo) is a combination of drugs given as a subcutaneous (under the skin) shot over several minutes.

Margetuximab (Margenza) can be used along with chemo to treat advanced breast cancer, typically after at least 2 other drugs that target HER2 have been tried. It’s given as an infusion into a vein (IV).

Antibody-drug conjugates

An antibody-drug conjugate (ADC) is a monoclonal antibody linked to a chemotherapy drug. In this case, the anti-HER2 antibody acts like a homing device by attaching to the HER2 protein on cancer cells, bringing the chemo directly to them.

These drugs are given as infusions into a vein (IV).

Ado-trastuzumab emtansine (Kadcyla or TDM-1) can be used to treat:

• Early-stage breast cancer after surgery, when chemo and trastuzumab were given before surgery, and there was cancer still present at the time of surgery
• Advanced breast cancer in men who have already been treated with trastuzumab and chemo

Fam-trastuzumab deruxtecan (Enhertu) can be used to treat:

• Breast cancer that can’t be removed with surgery or that has spread (metastasized) to another part of the body, typically after other anti-HER2 targeted drugs have been tried
• HER2-low breast cancer that can’t be removed with surgery or that has spread to another part of the body, typically after chemotherapy has been tried or if the cancer recurs within 6 months of finishing adjuvant chemotherapy

Kinase inhibitors

HER2 is a type of protein known as a kinase. Kinases are proteins in cells that normally relay signals (such as telling the cell to grow). Drugs that block kinases are called kinase inhibitors.

Lapatinib (Tykerb) is a pill taken daily to treat advanced breast cancer, typically along with the chemo drug capecitabine or with certain hormone therapy drugs.

Neratinib (Nerlynx) is a pill taken daily to treat early-stage breast cancer after completing one year of trastuzumab, and it is usually given for one year. It can also be given along with the chemo drug capecitabine to treat metastatic cancer, typically after at least 2 other anti-HER2 targeted drugs have been tried.

Tucatinib (Tukysa) is taken as a pill, typically twice a day. It’s used to treat advanced breast cancer, after at least one other anti-HER2 targeted drug has been tried. It is typically given along with trastuzumab and the chemo drug capecitabine.

Side effects of HER2 targeted drugs

The side effects of HER2 targeted drugs are often mild, but some can be serious. Talk to your cancer care team about what you can expect.

The monoclonal antibodies and antibody-drug conjugates can sometimes cause heart damage during or after treatment. This can lead to congestive heart failure. For most (but not all) people, this effect lasts a short time and gets better when the drug is stopped. The risk of heart problems is higher when these drugs are given with certain chemo drugs that also can cause heart damage, such as doxorubicin (Adriamycin) or epirubicin. Because these drugs can cause heart damage, doctors often check your heart function with an echocardiogram or a MUGA scan before and during treatment. Let your care team know if you develop symptoms such as shortness of breath, leg swelling, or severe fatigue.

Lapatinib, neratinib, tucatinib, and the combination of pertuzumab with trastuzumab can cause severe diarrhea, so it’s very important to let your care team know about any changes in bowel habits as soon as they happen.

Lapatinib and tucatinib can also cause hand-foot syndrome, in which the hands and feet become sore and red, and may blister and peel.

Lapatinib, neratinib, and tucatinib can cause liver problems. Your doctor will order blood tests to check your liver function during treatment. Let your care team know right away if you have possible signs or symptoms of liver problems, such as itchy skin, yellowing of the skin or the white parts of your eyes, dark urine, or pain in the right upper belly area.

Fam-trastuzumab deruxtecan (Enhertu) can cause serious lung disease, which might even be life-threatening. It’s very important to let your doctor or nurse know right away if you’re having symptoms such as coughing, wheezing, trouble breathing, or fever.

Targeted therapy for hormone receptor-positive breast cancer

Most breast cancers in men are hormone receptor (HR)-positive, meaning they are estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, or both.

These cancers are commonly treated with hormone therapy, but certain targeted therapy drugs can also be helpful.

CDK4/6 inhibitors

Palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) block proteins in the cell called cyclin-dependent kinases (CDKs), particularly CDK4 and CDK6. This helps stop the cells from dividing and can slow cancer growth.

These drugs can be used to treat hormone receptor-positive, HER2-negative breast cancer. There are different ways to use these drugs:

• For early-stage breast cancer that has spread to the lymph nodes and has a high chance of coming back after surgery, abemaciclib can be given as adjuvant treatment along with tamoxifen or an AI. It is typically given for 2 years.
• Any of these drugs can be given along with an aromatase inhibitor (AI) or fulvestrant to treat advanced breast cancer.
• Abemaciclib can also be used by itself for advanced breast cancer when hormone therapy and chemotherapy have already been tried.

These drugs are taken as pills, typically once or twice a day.

Side effects of CDK4/6 inhibitors

The most common side effects of CDK4/6 inhibitors are low blood cell counts and fatigue. Nausea and vomiting, mouth sores, hair loss, diarrhea, and headache are less common side effects. Very low white blood cell counts can increase the risk of serious infection.

A rare but possibly serious side effect is inflammation of the lungs, also called interstitial lung disease or pneumonitis.

PI3K inhibitors

Alpelisib (Piqray) and inavolisib (Itovebi) block a form of the PI3K protein in cancer cells. This can help stop them from growing.

These drugs can be used to treat advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA gene mutation that has grown during or after treatment with hormone therapy. (The PIK3CA gene is the gene that tells the cell to make the PI3K protein.) Your doctor will test your blood or tumor for this gene mutation before starting treatment with one of these drugs.

• Alpelisib is used along with the hormone drug fulvestrant.
• Inavolisib is used along with fulvestrant and the targeted drug palbociclib (see above).

These drugs are taken as pills, typically once a day.

Side effects of PI3K inhibitors

Side effects of these drugs can include skin rash, mouth sores, high blood sugar levels, signs of kidney, liver, or pancreatic problems, diarrhea, low blood counts, nausea and vomiting, fatigue, decreased appetite, weight loss, low calcium levels, blood clotting problems, and hair loss.

Some side effects can be more severe, and they might be more likely with one drug than with another. For example:

• Alpelisib is more likely to cause severe skin reactions, such as rashes with peeling and blistering, as well as serious lung inflammation (pneumonitis).
• Inavolisib is more likely to cause severe mouth sores.
• Both drugs might cause a person to have very high blood sugar levels or severe diarrhea.

AKT inhibitor

Capivasertib (Truqap) blocks forms of the AKT protein, which is part of a signaling pathway inside cells (including cancer cells) that can help them grow. Other proteins in this pathway include the PI3K and PTEN proteins.

This drug can be used along with the hormone drug fulvestrant to treat advanced hormone receptor-positive, HER2-negative breast cancer, if the cancer cells have changes in any of the PIK3CA, AKT1, or PTEN genes, and if the cancer has grown during or after treatment with hormone therapy. Your doctor will test your blood or tumor for these gene mutations before starting treatment with this drug.

This drug is taken as pills, typically twice a day for 4 days, followed by 3 days off each week.

Side effects of capivasertib

Side effects of this drug can include:

• High blood sugar levels: Your cancer care team will check your blood sugar levels before and during your treatment.
• Diarrhea (which may be severe): Tell your care team right away if you start to have loose stool or diarrhea.
• Skin rash or other skin reactions: Very severe skin reactions, such as rashes with peeling and blistering, are possible and should be reported to your care team.

Other possible side effects can include nausea, vomiting, mouth sores, skin rash, and changes in certain blood tests.

mTOR inhibitor

Everolimus (Afinitor) blocks mTOR, a protein in cells that normally helps them grow and divide. Everolimus may also stop tumors from developing new blood vessels, which can help limit their growth. It seems to help hormone therapy drugs work better against breast cancer.

This drug can be used to treat advanced hormone receptor-positive, HER2-negative, breast cancer. It is meant to be used with the hormone drug exemestane if the cancer has grown while being treated with either letrozole or anastrozole, or if the cancer started growing shortly after treatment with these drugs was stopped.

Everolimus is also being studied for earlier stage breast cancer and combined with other treatments. Although most of the people with breast cancer in studies of everolimus are women, some studies have included men.

Everolimus is taken as a pill, typically once a day.

Side effects of everolimus

Common side effects of this drug include mouth sores, diarrhea, nausea, fatigue, feeling weak or tired, low blood counts, shortness of breath, and cough. Everolimus can also increase blood lipids (cholesterol and triglycerides) and blood sugars, so your doctor will check your blood periodically while you are on this drug. It can also increase your risk of serious infections, so your care team will watch you closely for infection while you are on treatment.

Trop-2 antibody-drug conjugates

An antibody-drug conjugate (ADC) is a monoclonal antibody joined to a chemotherapy drug. The antibody acts like a homing device by attaching to a specific protein on cancer cells, bringing the chemo directly to them.

Sacituzumab govitecan (Trodelvy) and datopotamab deruxtecan (Datroway) attach to the Trop-2 protein on breast cancer cells, bringing the chemo directly to them. (In some breast cancers, the cells have too much Trop-2, which helps them grow and spread quickly.)

These ADCs can be used to treat advanced hormone receptor-positive, HER2-negative breast cancer when hormone therapy and chemotherapy have already been tried.

These drugs are given as infusions into a vein (IV):

• Sacituzumab govitecan is typically given once a week for 2 weeks, followed by 1 week off, then restarted.
• Datopotamab deruxtecan is typically given once every 3 weeks.

Side effects of Trop-2 antibody-drug conjugates

Common side effects of these drugs can include nausea, vomiting, diarrhea, constipation, feeling tired, rash, loss of appetite, hair loss, low red blood cell counts, and belly pain.

Serious side effects of sacituzumab govitecan can include very low white blood cell counts (with an increased risk of infection), severe diarrhea, and infusion reactions (similar to an allergic reaction) when the drug is infused.

Serious side effects of datopotamab deruxtecan can include severe lung problems, eye problems, and mouth sores, as well as infusion reactions (similar to an allergic reaction) when the drug is infused.

You will get medicines before each treatment with these drugs to lower the chances of vomiting and infusion reactions.

Targeted therapy for men with inherited BRCA gene mutations

PARP inhibitors

Olaparib (Lynparza) and talazoparib (Talzenna) target PARP proteins, which normally help repair damaged DNA inside cells. The BRCA genes (BRCA1 and BRCA2) also help repair DNA (in a slightly different way), but mutations in one of those genes can keep these repairs from happening. Because tumor cells with a mutated BRCA gene already have trouble repairing damaged DNA, blocking the PARP proteins often leads to the death of these cells.

Olaparib can be used to treat men with an inherited BRCA gene mutation with early-stage, HER2-negative breast cancer after surgery who have been treated with chemotherapy (before or after surgery) and are at high risk of the cancer recurring. It is typically given for 1 year.

Olaparib and talazoparib can be used to treat metastatic, HER2-negative breast cancer in people with an inherited BRCA gene mutation who have already gotten chemotherapy (and hormone therapy if the cancer is hormone receptor-positive).

Only a small portion of men with breast cancer have an inherited mutation in a BRCA gene, meaning the mutation is in every cell in the body and not only the cancer cells. If you are not known to have an inherited BRCA gene mutation, your doctor will test you for this mutation before starting treatment with one of these drugs.

These drugs come in pills that are taken once or twice a day.

Side effects of PARP inhibitors

Side effects of these drugs can include nausea, vomiting, diarrhea, fatigue, loss of appetite, taste changes, low red blood cell counts (anemia), low platelet counts, low white blood cell counts, belly pain, and muscle and joint pain.

Rarely, some people treated with a PARP inhibitor have developed a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia (AML).

Targeted therapy for triple-negative breast cancer

In triple-negative breast cancer (TNBC), the cancer cells don’t have estrogen or progesterone receptors, and they don’t make too much of the HER2 protein.

Trop-2 antibody-drug conjugate

An antibody-drug conjugate (ADC) is a monoclonal antibody joined to a chemotherapy drug. The antibody acts like a homing device by attaching to a specific protein on cancer cells, bringing the chemo directly to them.

Sacituzumab govitecan (Trodelvy): In this ADC, the monoclonal antibody part attaches to the Trop-2 protein on breast cancer cells and brings the chemo directly to them. (Some breast cancer cells have too much Trop-2, which helps them grow and spread quickly.)

This ADC can be used by itself to treat advanced TNBC, typically after other chemo regimens have been tried. It’s given as an infusion into a vein (IV), typically weekly for 2 weeks, followed by 1 week off, then restarted.

Side effects of sacituzumab govitecan

Common side effects of this drug include nausea, vomiting, diarrhea, constipation, feeling tired, rash, loss of appetite, hair loss, low red blood cell counts, and belly pain.

Serious side effects can include very low white blood cell counts (with an increased risk of infection), severe diarrhea, and infusion reactions (similar to an allergic reaction) when the drug is infused.

Medicines are normally given before each treatment to lower the chances of vomiting and infusion reactions.

Drugs that target cells with NTRK gene changes

In a small number of breast cancers, the cells have changes in one of the NTRK genes. This causes them to make abnormal TRK proteins, which can lead to abnormal cell growth and cancer.

Larotrectinib (Vitrakvi), entrectinib (Rozlytrek), and repotrectinib (Augtyro) target the TRK proteins, so they are called TRK inhibitors. These drugs can be used to treat advanced cancers with NTRK gene changes that are still growing despite other treatments.

These drugs are taken as pills or a liquid, once or twice daily.

Side effects of TRK inhibitors

Common side effects of these drugs can include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea.

Less common but serious side effects can include abnormal liver tests, increased risk for fractures, heart problems, vision changes, and confusion.

Other targeted therapy drugs

Some other targeted drugs might be useful in certain circumstances. For example:

• Selpercatinib (Retevmo), a drug that targets the RET protein, can be used to treat advanced cancers with RET gene changes that are still growing despite other treatments.
• Dabrafenib (Tafinlar) and trametinib (Mekinist) might be an option to treat cancers with a BRAF gene change known as a V600E mutation.