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As researchers have learned more about changes in cancer cells that cause them to grow out of control, they've developed new types of drugs that target some of these cell changes. These targeted drugs work differently from chemotherapy (chemo) drugs.

Targeted drugs sometimes work even when chemo drugs do not. Some targeted drugs can help other types of treatment work better. Targeted drugs also tend to have different side effects than chemo. 

Several targeted drugs have been approved for use in treating breast cancer, although using these drugs in men is often based largely on how well they work in women.

Targeted therapy for HER2-positive breast cancer

In some men with breast cancer, the cancer cells have too much of a growth-promoting protein known as HER2 (or HER2/neu) on their surface. These cancers, known as HER2-positive breast cancers, tend to grow and spread more aggressively.

Different types of drugs have been developed that target the HER2 protein.

Monoclonal antibodies

Monoclonal antibodies are man-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, other brand names): Trastuzumab 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 (neoadjuvant) or after (adjuvant) surgery 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. This drug is given into a vein (IV).

Another form of trastuzumab, called trastuzumab and hyaluronidase injection (Herceptin Hylecta), is also available. It is given as a subcutaneous (under the skin) shot over a few minutes.

Pertuzumab (Perjeta): This monoclonal antibody can be given with trastuzumab and chemo, either before or after surgery to treat early-stage breast cancer, or to treat advanced breast cancer. This drug is given into a vein (IV).

For people getting both of these monoclonal antibodies as part of their treatment, a combination of trastuzumab, pertuzumab, and hyaluronidase (Phesgo) is also available as a single injection. It is given as a subcutaneous (under the skin) shot over several minutes.

Margetuximab (Margenza): This monoclonal antibody can be used along with chemo to treat advanced breast cancer, typically after at least 2 other drugs that target HER2 have been tried. This drug is given 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 signal by attaching to the HER2 protein on cancer cells, bringing the chemo directly to them.

Ado-trastuzumab emtansine (Kadcyla or TDM-1): This antibody-drug conjugate is used by itself 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), or to treat advanced breast cancer in men who have already been treated with trastuzumab and chemo. This drug is given in a vein (IV).

Fam-trastuzumab deruxtecan (Enhertu): This antibody-drug conjugate can be used by itself to treat breast cancer that can’t be removed with surgery or that has spread (metastasized) to another part of the body, typically after at least 2 other anti-HER2 targeted drugs have been tried. This drug is given in a vein (IV).

Fam-trastuzumab deruxtecan can also be used to treat HER2-low breast cancers 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): This drug is a pill taken daily. Lapatinib is used to treat advanced breast cancer, typically along with the chemo drug capecitabine or with certain hormone therapy drugs.

Neratinib (Nerlynx): This kinase inhibitor is a pill taken daily. Neratinib is used 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 people with metastatic disease, typically after at least 2 other anti-HER2 targeted drugs have been tried.

Tucatinib (Tukysa): This kinase inhibitor is taken as pills, typically twice a day. Tucatinib is 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. Discuss what you can expect with your doctor.

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) and epirubicin (Ellence). Because these drugs can cause heart damage, doctors often check your heart function (with an echocardiogram or a MUGA scan) before treatment, and regularly while you are taking the drug. Let your doctor know if you develop symptoms such as shortness of breath, leg swelling, and severe fatigue.

Lapatinib, neratinib, tucatinib, and the combination of pertuzumab with trastuzumab can cause severe diarrhea, so it’s very important to let your health 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 do blood tests to check your liver function during treatment. Let your health 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 in some people. In some cases this 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

In about 9 out of 10 men with breast cancer, the breast cancer cells have proteins (receptors) on the outside that can attach to hormones, like estrogen or progesterone, to help them grow. These are called hormone receptor-positive (HR-positive) breast cancers. Sometimes they are called estrogen receptor-positive (ER-positive) or progesterone receptor-positive (PR-positive) breast cancers. These cancers are commonly treated with hormone therapy. Certain targeted therapy drugs can make hormone therapy even more effective, although these targeted drugs might also add to the side effects.

CDK4/6 inhibitors

Palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) are drugs that block proteins in the cell called cyclin-dependent kinases (CDKs), particularly CDK4 and CDK6. Blocking these proteins in hormone receptor-positive breast cancer cells helps stop the cells from dividing. This can slow cancer growth.

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

• For men with 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 in men with advanced breast cancer who have previously been treated with hormone therapy and chemotherapy.

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

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 possible life-threatening 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, which can help stop them from growing.

These drugs can be used to treat men with 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 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 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 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 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 cancer team right away if 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 a doctor. 

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

mTOR inhibitor

Everolimus (Afinitor) is a targeted drug known as an mTOR inhibitor. It 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. When used for treating breast cancer, this drug seems to help hormone therapy drugs work better.

This drug is approved to treat advanced hormone receptor-positive, HER2-negative, breast cancer in women who have gone through menopause. It is meant to be used with exemestane (Aromasin) in these women if their cancers have grown while they were 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 use 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.

Common side effects of everolimus 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 work periodically while you are on this drug. It can also increase your risk of serious infections, so your doctor will watch you closely for infection while you are on treatment.

Antibody-drug conjugate

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

Sacituzumab govitecan (Trodelvy): In the case of 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 to treat advanced hormone receptor-positive, HER2-negative breast cancer, in people who have already received hormone therapy and at least 2 chemo regimens. 

This drug is given into a vein (IV) weekly for 2 weeks, followed by one week off, then restarted.

Some 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.

Targeted therapy for men with BRCA mutations

Olaparib (Lynparza) and talazoparib (Talzenna) are drugs known as PARP inhibitors. PARP proteins 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 stop this from happening. PARP inhibitors work by blocking the PARP proteins. 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 and talazoparib can be used to treat metastatic, HER2-negative breast cancer in patients with a BRCA mutation who have already gotten chemotherapy (and hormone therapy if the cancer is hormone receptor-positive).

Only a portion of men with breast cancer have a mutated BRCA gene that they are born with, and which is in all the cells of the body (as opposed to the gene change being acquired and found only in the cancer cells). If you are not known to have a BRCA mutation, your doctor will test your blood to be sure you have one before starting treatment with one of these drugs.

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

Side effects 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 make very little or none of the HER2 protein.

Antibody-drug conjugate

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

Sacituzumab govitecan (Trodelvy): In the case of 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 antibody-drug conjugate can be used by itself to treat advanced TNBC, after at least 2 other chemo regimens have been tried. This drug is given in a vein (IV) weekly for 2 weeks, followed by one week off, then restarted.

Some 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.