Targeted Therapy for Breast Cancer in Men
As researchers have learned more about the gene changes in cells that cause cancer, they have been able to develop newer drugs that specifically target these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs. They often have different (and less severe) side effects.
Drugs that target the HER2/neu protein
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. Breast cancers with too much of this protein are called HER2 positive. They tend to grow and spread more aggressively without special treatment. A number of drugs have been developed that target this protein. As with many of the other treatments for breast cancer, studies of these drugs included few, if any men, so using them in men is based on how well they work in women.
Trastuzumab (Herceptin): Trastuzumab is a monoclonal antibody, a man-made version of a very 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 is used as a part of adjuvant (or neoadjuvant) therapy for early stage HER2-positive cancers to reduce the risk of the cancer coming back. It is given first with chemo, then by itself to complete a year of treatment.
Trastuzumab is also used to treat HER2-positive advanced breast cancers that return after chemo or continue to grow during chemo. Often, trastuzumab is combined with chemo. . If the cancer gets worse while on trastuzumab and chemo, often the trastuzumab is continued and the chemo is changed.
Compared with chemo drugs, the side effects of trastuzumab are relatively mild. These occur rarely and 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. People having these symptoms should call their doctor right away.
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.
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 given as an infusion into a vein 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 tests of 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 (hand-foot syndrome was discussed in the section “ Chemotherapy for breast cancer in men”). 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.
Everolimus is a pill taken once a day to block mTOR, a protein in cells that normally promotes their growth and division. 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 anastrazole (or the cancer started growing shortly after stopping treatment with these drugs). It has also been studied for use with other hormone therapy drugs. It may help hormone drugs work better in men who have hormone-receptor positive breast cancer, but this has not been studied.
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.
More information about monoclonal antibodies can be found in Immunotherapy.
General information about targeted therapy can be found in Targeted Therapy.
Last Medical Review: October 10, 2014 Last Revised: January 26, 2016
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