Targeted Therapy for Breast Cancer in Men

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 are designed to block the growth and spread of cancer cells. These targeted drugs work differently from chemotherapy drugs, which attack all cells that are growing quickly (including cancer cells).

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. There are many targeted therapies being studied for use in breast cancer. Several of these therapies have been approved for use in treating breast cancer, though many studies have included very few men, if any. Using targeting therapies in men is often based 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/neu (or just HER2) on their surface. These cancers, known as HER2-positive breast cancers, tend to grow and spread more aggressively.

A number of drugs have been developed that target this protein.

Trastuzumab (Herceptin)

This is a monoclonal antibody, which is a man-made version of a specific immune system protein. It attaches to HER2 and can help slow the growth of cancers that are HER2-positive. Trastuzumab may also stimulate the immune system to more effectively attack the cancer.

Trastuzumab is injected into a vein (IV), usually once a week or at a larger dosage once every 3 weeks.

Trastuzumab can be used to treat both early- and late-stage breast cancer. When started before or after surgery to treat early breast cancer, this drug is usually given for a total of a year. For advanced breast cancer, treatment is often given for as long as the drug is helpful. Trastuzumab is often combined with chemo, but might also be used alone.

The side effects of trastuzumab tend to be relatively mild. They may include fever and chills, weakness, nausea, vomiting, cough, diarrhea, and headache. These side effects are less common after the first dose.

A more serious potential side effect is heart damage that can lead to a problem called congestive heart failure. For most (but not all) people, this effect is temporary and improves when the drug is stopped. The risk of heart problems is higher when trastuzumab is given with chemo drugs that also cause heart damage such as doxorubicin (Adriamycin) or epirubicin (Ellence). Because this drug can cause heart damage, your heart function will be checked before treatment with a test like an echocardiogram or a MUGA. It will be checked again every few months during treatment with trastuzumab. Major symptoms of congestive heart failure are leg swelling, shortness of breath, and severe fatigue. Tell your doctor right away if you have any of these symptoms.

Ado-trastuzumab emtansine (TDM-1, Kadcyla)

Ado-trastuzumab emtansine is a type of drug known as an antibody-drug conjugate. It is made up of the same monoclonal antibody found in trastuzumab attached to a chemo drug known as DM-1. In this type of drug, the antibody acts as a homing device, taking the chemo drug directly to the cancer cells.

This drug is injected into a vein (IV) every 3 weeks. Common side effects include fatigue, nausea, muscle and bone pain, low platelet counts, headache, and constipation. This drug can also cause more serious side effects, such as severe allergic reactions, liver damage, heart damage, and lung problems.

Fam-trastuzumab deruxtecan (Enhertu)

This is another antibody-drug conjugate, in which the anti-HER2 antibody acts as a homing device, taking the chemo drug directly to the cancer cells. This drug 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 at least 2 other anti-HER2 targeted drugs have been tried.

This drug is injected into a vein (IV) once every 3 weeks. 

Common side effects can include fatigue, nausea, vomiting, diarrhea, constipation, loss of appetite, and hair loss. Less common but more serious side effects can include heart damage and low white blood cell counts, which can lead to an increased risk of serious infection.

This drug can also cause serious lung disease in some people, which in some cases 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.

Pertuzumab (Perjeta)

Like trastuzumab, pertuzumab is a monoclonal antibody that attaches to the HER2 protein. It seems to target a different part of the protein than trastuzumab does. This drug can be used along with docetaxel (Taxotere) and trastuzumab to treat patients with advanced breast cancer. This 3 drug combination can also be used to treat earlier-stage breast cancers before surgery (as neoadjuvant therapy).

This drug is injected into a vein (IV) every 3 weeks. When given with trastuzumab and docetaxel, common side effects included diarrhea, hair loss, nausea, fatigue, rash, and low white blood cell counts (sometimes with fever). Many side effects, such as hair loss, nausea, and fatigue occur at about the same rate as in those who get just docetaxel and trastuzumab. Like trastuzumab, pertuzumab can weaken the heart and cannot be taken if you already have poor heart function. Your doctor will check your heart function before starting this drug and again every few months during treatment with pertuzumab.

Lapatinib (Tykerb)

Lapatinib is another drug that targets the HER2 protein. This drug is taken as a pill, most often along with the chemo drug capecitabine (Xeloda). It is used to treat advanced, HER2-positive breast cancer that is no longer helped by chemotherapy and trastuzumab. It is usually given with chemo.

The most common side effects with this drug include diarrhea, rash, and hand-foot syndrome. (See Chemotherapy for Breast Cancer in Men for more information about hand-foot syndrome.) Diarrhea is a common side effect and can be severe, so it is very important to let your health care team know about any changes in bowel habits as soon as they happen. In rare cases lapatinib may cause liver problems or a decrease in heart function (that can lead to shortness of breath), but this seems to go away once treatment is finished.

Neratinib (Nerlynx)

This is a drug that targets the HER2 protein. It is a pill that is taken daily. Neratinib is used to treat early-stage breast cancer after a man has completed one year of trastuzumab and is usually given for one year. Some clinical trials show that it may also be effective in advanced breast cancer, as well.

Targeted therapy for hormone receptor-positive breast cancer

About 9 out of 10 men with breast cancer will have breast cancer that is affected by hormones in the blood. These breast cancer cells have a protein on the outside that can attach to hormones, like estrogen or progesterone, to help them grow. This is called hormone receptor-positive (HR-positive) breast cancer. Sometimes these are called ER- (estrogen receptor-) positive or PR- (progesterone receptor-) positive breast cancers. These cancers are commonly treated with hormone therapy, but there are also some targeted therapies approved for use in men with hormone receptor-positive breast cancer.

CDK4/6 inhibitors

Abemaciclib (Verzeniois a drug 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. Abemaciclib is approved for use in men with HR-positive, HER2-negative advanced breast cancer that has gotten worse after treatment with hormone therapy and chemotherapy. Abemaciclib is taken as pills, typically twice a day.

Palbociclib (Ibrance) and ribociclib (Kisqali) are also drugs that block the CDK4 and CDK6 proteins. They can be used along with certain hormone therapy drugs such as fulvestrant or an aromatase inhibitor (such as letrozole) in patients who have advanced HR-positive, HER2-negative breast cancer (although ribociclib is not approved specifically for use in men). These drugs are taken as pills, typically once a day for 3 weeks at a time, with a week off before starting again.

Side effects of these drugs tend to be mild. The most common side effects 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.

Everolimus (Afinitor)

Everolimus is a pill taken once a day to block mTOR, a protein in cells that normally helps them grow and divide. By blocking this protein, everolimus can help stop cancer cells from growing. Everolimus may also stop tumors from developing new blood vessels, which can help limit their growth. In 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). It has also been studied for use with other hormone therapy drugs.

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.

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 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.

Targeted therapy for men with BRCA mutations

Olaparib (Lynparza) is a type of drug known as a PARP inhibitor. 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 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). 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 this drug.

This drug comes in pills that are taken once a day.

Side effects can include nausea, vomiting, diarrhea, fatigue, loss of appetite, taste changes, low red blood cell counts (anemia), 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 cancers with a PIK3CA gene mutation

Alpelisib (Piqray) is a targeted drug known as a PI3K inhibitor. It can be used along with fulvestrant to treat men with advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation that has grown during or after treatment with an aromatase inhibitor. About 30-40% of breast cancers have a mutated PIK3CA gene. Your doctor will test your blood or tumor for this mutation before starting treatment with this drug.

This drug comes in pills that are taken once a day.

Side effects can include high blood sugar levels, signs of kidney, liver, or pancreatic problems, diarrhea, rash, low blood counts, nausea and vomiting, fatigue, decreased appetite, mouth sores, weight loss, low calcium levels, blood clotting problems, and hair loss. Very severe skin reactions, such as rashes with peeling and blistering, are possible and should be reported to a doctor. Patients with a history of severe skin reactions should tell their doctor before taking alpelisib.

More information about targeted therapy

To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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Last Medical Review: April 27, 2018 Last Revised: December 23, 2019

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