Treatment For Her2 Breast Cancer

Prognosis For Metastatic Her2+ Cancer

Generally, when breast cancer becomes metastatic, it is not possible to cure the cancer. This does not mean that the cancer isnt treatable, though. Data from the National Cancer Institute estimates that for those diagnosed with metastatic breast cancer, 29% have a five-year survival rate. This means that 29% of the people with that cancer are still alive in five years.

Summary Of Treatment Options For Metastatic Breast Cancer

Hormone receptor-positive, HER2-negative breast cancer

Hormonal therapy is considered the standard initial treatment for HER2-negative metastatic breast cancer that is also hormone receptor-positive. It is often given in combination with targeted therapy. However, chemotherapy may also be given. A clinical trial may also be an option for treatment at any stage.

Hormone receptor-negative, HER2-negative breast cancer

In general, chemotherapy or targeted therapy is given for treatment of triple-negative breast cancer. A clinical trial may also be an option for treatment at any stage.

HER2-positive breast cancer that has spread to parts of the body other than the brain

In general, HER2-targeted therapy is regularly added to treatment for HER2-positive breast cancer that has spread. The drugs used depend on the treatments already given and whether the cancer is hormone receptor-positive. The treatment recommendations for first-line, second-line, and third-line or higher treatment are described below. A clinical trial may also be an option for treatment at any stage.

First-line treatment

Second-line treatment

• For people with advanced breast cancer that has grown during or after first-line treatment with a HER2-targeted therapy, ASCO recommends trastuzumab deruxtecan as a second-line treatment.

Third-line or higher treatment

HER2-positive breast cancer that has spread to the brain

Your Treatment Is Unique

HER2-positive breast cancer is different from other breast cancer types, so your treatment wonât necessarily be the same as someone else who has a different form of breast cancer. It may also be different than another HER2-positive patientâs therapy.

Each cancer is unique, so doctors try to develop the treatment course thatâs best for you. Things to consider include the size of your tumor, whether the cancer has metastasized , or your overall risk of recurrence.

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Heart Problems Linked To Trastuzumab

Trastuzumab use is linked to congestive heart failure, a serious heart condition.

In clinical trials, about 2-3 percent of those treated with chemotherapy plus trastuzumab had heart failure, compared to fewer than 1 percent of those treated with chemotherapy alone .

This risk of heart problems is higher with chemotherapy regimens that include an anthracycline drug compared to regimens without an anthracycline drug .

The risk of heart problems may also be higher for women over 60 and for those who already have heart problems .

For most people who develop a heart problem while taking trastuzumab, the condition improves after stopping trastuzumab. For a few, it may be permanent.

Avoiding heart problems

Your heart will be checked before and during treatment with trastuzumab. This is to help make sure there are no problems, or if there are problems, theyre caught early.

Adopting a lifestyle that includes a healthy diet, regular exercise and for those who smoke, quitting smoking are good ways to help avoid heart problems related to treatment.

To learn more about trastuzumab, visit the National Institutes of Healths Medline Plus website.

What Is Her2 And What Does It Mean

HER2 is a protein that helps breast cancer cells grow quickly. Breast cancer cells with higher than normal levels of HER2 are called HER2-positive. These cancers tend to grow and spread faster than breast cancers that are HER2-negative, but are much more likely to respond to treatment with drugs that target the HER2 protein.

All invasive breast cancers should be tested for HER2 either on the biopsy sample or when the tumor is removed with surgery.

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How Do We Test Her2 Status

Two tests are used to check HER2 status:

• An immunohistochemistry test: During an IHC test, antibodies attach to the target antigen on a cell. Chemicals are used to stain cells so they can be seen under a microscope. For breast cancer, the antigen is the HER2 protein.
• Fluorescence in situ hybridization test: The FISH test uses fluorescent dyes to highlight chromosomal changes in genes. For breast cancer, it highlights amplification of the HER2 protein.

Doctors may use one or both of these tests to diagnose breast cancer, gauge how it responds to treatment and see whether its recurred. IHC testing typically comes first because its more affordable and faster than FISH, but FISH is considered more accurate.

Have Low White Blood Cell Counts

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving intravenous trastuzumab plus chemotherapy than in patients receiving chemotherapy alone.

Your doctor may check for signs of low white blood cell counts when he or she examines you.

Experience HYPERSENSITIVITY AND ADMINISTRATION-RELATED REACTIONS, which have been reported with HERCEPTIN HYLECTA. Serious and fatal reactions have been reported after treatment with intravenous trastuzumab products. Your doctor will monitor you for signs of these reactions. Contact your healthcare provider immediately if you experience any symptoms of hypersensitivity and administration-related reactions, including dizziness, nausea, chills, fever, vomiting, diarrhea, hives, swelling under the skin, breathing problems, or chest pain.

SIDE EFFECTS SEEN MOST OFTEN

The most common side effects seen in treatment of adjuvant breast cancer with HERCEPTIN HYLECTA were tiredness, joint pain, diarrhea, injection site reaction, upper respiratory tract infection, rash, muscle pain, nausea, headache, swelling, flushing, fever, cough, and pain in extremity.

The most common side effects seen in treatment of metastatic breast cancer are fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash.

You should contact your doctor immediately if you have any of the side effects listed above.

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Trastuzumab Targets Breast Cancer In Clinical Trials

Researchers launched three clinical trials of trastuzumab in the mid-1990s for patients with HER2-positive metastatic breast cancer. By 1998, the results of the phase 3 clinical trials showed that breast cancer in patients treated with trastuzumab and chemotherapy grew at a slower rate than in patients treated with chemotherapy alone. Subsequent clinical trials also showed positive outcomes among women with early-stage HER2-positive breast cancer.

On November 16, 2006, the US Food and Drug Administration granted approval to trastuzumab used with chemotherapy as an adjuvant treatment for women with HER2-positive breast cancer. The drug has improved survival rates for women with stage 1 to 3 HER2-positive breast cancer by more than 30 percent.

HER2 protein is expressed at high levels in several other cancers besides breast cancer, and in 2010, FDA approved the use of trastuzumab in combination with the chemotherapy drug cisplatin and a type of cancer drug called a fluoropyrimidine to treat some patients with HER2-positive gastric or gastroesophageal junction cancers.

Side Effects Of Neratinib

The most common side effect of neratinib is diarrhea . Your health care provider will recommend medications to help control the diarrhea.

Other side effects include nausea, abdominal pain, fatigue, vomiting and rash . More serious health risks include liver damage .

To learn more about neratinib, visit the National Institutes of Healths Medline Plus website.

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Side Effects Of Her2 Targeted Drug Therapy

The side effects of HER2 targeted drugs are often mild, but some can be serious. Discuss what you can expect with your doctor. If you are pregnant, you should not take these drugs. They can harm and even cause death to the fetus. If you could become pregnant, talk to your doctor about using effective birth control while taking these drugs.

Monoclonal antibodies and antibody-drug conjugates can sometimes cause heart damage during or after treatment. This can lead to congestive heart failure. For most women, 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 and epirubicin . Other factors that can increase your risk of heart problems are being older than 50, being overweight or obese, having heart problems, and taking medicines for high blood pressure.

Because these drugs can cause heart damage, doctors often check your heart function before treatment, and regularly while you are taking the drug. Let your doctor know if you develop symptoms such as shortness of breath, a fast heartbeat, leg swelling, and severe fatigue.

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

What Are Immune Checkpoints

Immune “checkpoints” are proteins that usually help your immune system distinguish between healthy and dangerous cells. Breast cancer cells can mimic checkpoint proteins to avoid being detected by the immune system.

One IV drug, Keytruda , targets a checkpoint protein called PD-1. By blocking PD-1, Keytruda can expose and boost the immune response against breast cancer cells, which can often shrink the cancer.

Keytruda is used with chemotherapy to treat triple-negative breast cancer, which is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative.

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How Metastatic Breast Cancer Is Treated

In cancer care, different types of doctors often work together to create a patients overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Breast cancer multidisciplinary care teams typically include medical oncologists, surgical oncologists, radiation oncologists, radiologists, and pathologists. In addition, cancer care teams include a variety of other health care professionals, such as physician assistants, nurse practitioners, oncology nurses, genetic counselors, social workers, pharmacists, counselors, dietitians, financial advisors, and other supportive care members. Ask the doctor in charge of your treatment which health care professionals will be part of your treatment team and what they do. This can change over time as your health care needs change.

A treatment plan is a summary of your cancer and the planned cancer treatment. It is meant to give basic information about your medical history to any doctors who will care for you during your lifetime. Before treatment begins, ask your doctor for a copy of your treatment plan. The treatment plan can be updated over time as your treatments change.

The main goals of metastatic breast cancer treatment are to make sure that you have the:

• Longest survival possible with the disease

• Fewest possible side effects from the cancer and its treatment

• Best and longest quality of life possible

Treatment options for metastatic breast cancer vary based on:

Factors That Affect Outlook

When considering your outlook, your doctor must analyze many other factors as well. Among them are:

• Stage at diagnosis. Your outlook is better when the breast cancer hasnt spread outside the breast or has spread only regionally at the start of treatment. Metastatic breast cancer, which is cancer that has spread to distant areas of the body, is harder to treat.
• Size and grade of primary tumor. This indicates how aggressive the cancer is.
• Lymph node involvement. Cancer can spread from the lymph nodes to distant organs and tissues.
• HR status and HER2 status. Targeted therapies can be used for HR-positive and HER2-positive breast cancers.
• Overall health. Other health issues you may have may complicate treatment.
• Response to therapy. Its hard to predict whether a particular therapy will be effective or produce intolerable side effects.
• Age. Younger women and those over age 75 may have a worse outlook than middle-aged women, except for those with stage 3 breast cancer, according to a .

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Blocking Her2 Slows Or Stops Some Types Of Breast Cancer

NCI-funded researcher Dennis Slamon, M.D., was among the many scientists searching for genes that can lead to cancer. In 1987, he and his colleagues discovered that the growth factor receptor gene HER2, which produces HER2 proteins, might be a good candidate.

At the same time, a team of NCI researchers led by Stuart Aaronson, M.D., were among the first to show that the HER2 protein could cause normal cells to grow uncontrollably like aggressive cancer cells.

Dr. Slamons team found that the HER2 protein is present at high levels in about 30 percent of breast cancers. They also discovered that high levels of HER2 are linked to a greater likelihood of metastasis and relapse and an overall decrease in patient survival. The group concluded that HER2 might play a role in the development and growth of breast cancer.

NCI-funded researcher Dennis J. Slamon, M.D., discovered the genetic link between HER2 and breast cancer.

This led researchers to a groundbreaking hypothesis: If HER2 could be blocked, the growth of HER2-positive breast cancer might be slowed.

One way to block the action of a protein is to use laboratory-made monoclonal antibodies that attach to a specific protein and disrupt its function. With NCI support, Dr. Slamon and colleagues from the University of Texas Health Sciences Center had a breakthrough. They showed that an antibody specific to HER2 could slow the growth of metastatic breast cancer cells and other types of cancer in a laboratory dish.

Coping With Your Diagnosis

Being diagnosed with metastatic HER2-positive breast cancer can cause a lot of feelings. It is a life-altering diagnosis, and feelings can range from fear to anger. Finding support from friends or family can be important as you go through the steps of diagnosis and treatment. There are many support groups, both in person and virtual, as well as many websites with helpful information in navigating this journey.

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When Herceptin Is Used

Herceptin can be used to treat:

• early-stage HER2 positive breast cancer, following surgery and/or radiotherapy and chemotherapy, to reduce the risk of the cancer coming back
• advanced HER2 positive breast cancer that has spread from the breast , to slow the growth of the cancer and increase survival time
• advanced HER2 positive stomach cancer that has spread out of the stomach
• advanced HER2 positive gastro-oesophageal cancer, which affects where the food pipe meets the stomach

If you have breast, oesophageal or stomach cancer, you will have tests to check if the cancer is HER2 positive before herceptin is offered.

How Will Her2 Status Affect Treatments

Standard treatment for most breast cancer starts with surgically removing the tumor, followed by radiation therapy, chemotherapy or a combination of both. Doctors may try other drugs and approaches, such as immunotherapy, depending on the patients general health and the cancers characteristics.

For HER2-positive breast cancer, treatment may also include three kinds of targeted therapy:

• Monoclonal antibodies are manmade antibodies that stick to HER2 receptors to slow tumor growth.
• Antibody-drug conjugates, which are monoclonal antibodies combined with a chemotherapy drug. They deliver chemotherapy directly to cancer cells using antibodies that stick to the HER2 proteins.
• Kinase protein inhibitors block signals from the protein. HER2 is a kinase protein.

Side effects of these treatments vary. While most are mild, there may be some serious side effects:

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High Tumor Responses With Trastuzumab Deruxtecan

The DESTINY-Breast01 trial was not a randomized study, so all patients in the trial received trastuzumab deruxtecan.

Nearly all of the more than 180 women in the trial had at least some reduction in the size of their tumors, with 61% experiencing substantial reductions, Dr. Krop reported. Several patients had no evidence of cancer following treatment, known as a complete response. The median progression-free survival was more than 16 months.

Dr. Krop called the results compelling, noting that the tumor response rate is roughly double or triple what we typically see in other studies of this third- or later-line population.

Most of the treatment-related side effects seen in the trial were mild, Dr. Krop said. Even so, 15% of the participants stopped taking the drug because of side effects. Nearly all of these women were those who experienced ILD. Four of the women who developed ILD died as a result.

Why we have this particular risk is unclear, he said. And clearly we need to do more research to identify those patients who are at risk of getting the most severe cases of ILD and how to mitigate the risk.

For future studies of the drug, Dr. Krop said, clinicians will be advised to carefully monitor patients for any evidence or symptoms of ILD and, if they suspect it has developed, to immediately stop the drug and treat the patient with steroids.

We definitely have to be cautious, he continued. But I dont think is a major barrier to moving this drug forward.