Biologics for HR+ Breast Cancer: Know the Basics

PARP inhibitors

PARP inhibitors block PARP proteins, which normally help fix damaged DNA in cells. PARP inhibitors are only an option if you have advanced HR+, HER2-negative breast cancer with a BRCA gene mutation. BRCA1 and BRCA2 are the most common genes that cause hereditary breast cancer, which means the cancer is passed down from a parent. But researchers believe only about 5% to 10% of breast cancers are hereditary. 

mTOR inhibitor

Everolimus blocks the mTOR protein, which normally helps cells grow. This drug is an option if you have advanced, HR+, HER2-negative breast cancer. Doctors think it helps hormone therapy medicines work better. 

Which Biologics Are Used to Treat HR+ Breast Cancer?

Many biologic medicines are used to treat HR+ breast cancer. These include:

Some of the biologics (CDK4/6 inhibitors, an mTOR inhibitor, and a PI3K inhibitor) also are kinase inhibitors.

Biologic for HER2-positive, -low, and -ultra low breast cancer

Fam-trastuzumab deruxtecan (Enhertu), which is also an antibody-drug conjugate, is approved for HER2-positive, HER2-low, and HER2-ultra low, but not HER2-negative breast cancer. Your doctor might prescribe it if you’ve already tried chemotherapy, hormonal therapy, or an anti-HER2 medication. It’s given as an IV every three weeks unless the cancer grows. Similar to most breast cancer medications, some of the most common side effects include constipation, vomiting, hair loss, and fatigue.

Enhertu has two main parts, including fam-trastuzumab, the antibody part, which stops the HER2 protein from getting signals to grow, and a chemotherapy part called DXd, which works to try to keep the cell from growing and dividing.

HER2-low and HER2-ultra low used to be classified as HER2-negative breast cancer. HER2-low has IHC scores of 1 or 2; HER2-ultra low has a score of 0 (same as HER2-negative). HER2-low and HER2-ultra low are now separate categories. Some experts think of them as being a subcategory of HER2-negative – especially if the score is IHC 1 – because the conditions have many similarities.

Some biologics aren’t given to treat cancer. Instead, they’re used to relieve the side effects of breast cancer therapies.

Your doctor can help you decide which biologic treatment would be most helpful. 

Biosimilars used for HR+ breast cancer

Some biosimilars treat the side effects of chemotherapy or hormone therapy for HR+ breast cancer. These drugs copy the biologic medicines denosumab, filgrastim, and pegfilgrastim. 

When Are Biologics Prescribed for HR+ Breast Cancer?

Biologics target specific features on breast tumors. Doctors will perform special tests – like blood tests, saliva tests, or a biopsy – to figure out the makeup of your cancer. With a biopsy, a small amount of tissue is removed from your tumor and sent to a lab to study. 

A biopsy can show whether you have abnormal amounts of a protein called human epidermal growth factor (HER2) or other gene defects. Doctors will perform special tests on the biopsied tissue to figure out which biologics will be helpful. Here’s a breakdown of which HR+ breast cancers may benefit from biologics:

• HR+, HER2-negative: CDK4/6 inhibitors, the antibody-drug conjugate sacituzumab govitecan, and the mTOR inhibitor everolimus are used for breast cancers that don’t have a lot of the HER2 protein.
• HR+, HER2-negative with PIK3CA gene mutation: Alpelisib is an option for breast cancers that test negative for HER2 and have a PIK3CA gene mutation.
• HR+, HER2-negative with BRCA gene mutation: A PARP inhibitor can be helpful if you have a BRCA gene mutation and breast cancer that tests negative for the HER2 protein.

Certain biologics are combined with other medicines, and some are used alone. Here are some examples:

• Abemaciclib, palbociclib, and ribociclib can all be given to treat advanced breast cancer. They are used along with hormone therapy medicines, such as an aromatase inhibitor or the drug fulvestrant. These medicines are options if you’ve gone through menopause. Or you take them if you’ve had your ovaries surgically removed or take medicines to stop your ovaries from making estrogen. Abemaciclib can be used on its own if you have advanced breast cancer that’s previously been treated with hormone therapy and chemo. You can also take abemaciclib if you have early-stage breast cancer that’s spread to your lymph nodes and is likely to come back after surgery. In this case, abemaciclib is given with an aromatase inhibitor or the medicine tamoxifen. 
• Alpelisib can be used with the hormone drug fulvestrant if you have advanced breast cancer that grew during or after receiving treatment with an aromatase inhibitor.
• Olaparib is an option for early-stage cancer after surgery if you’ve been treated with chemo and are at high risk for your cancer returning. Or it can be used for advanced breast cancer if you’ve already had chemo or hormone therapy.   
• Sacituzumab govitecan can be given if you have locally advanced breast cancer that can’t be surgically removed and have received hormone therapy and at least two rounds of chemotherapy.
• Talazoprarib can be used to treat advanced breast cancer if you’ve already had chemotherapy.

How Do You Take Biologics?

Biologic medicines can be taken in different ways. 

Oral Tablets:Many biologic medicines are taken by mouth. Abemaciclib, alpelisib, everolimus, olaparib, palbociclib, ribociclib, and talazoparib come in pill form. It depends on the drug, but they’re usually taken one to two times a day.

Injections:Other biologics can be given as a shot under your skin. Some biologics are given via an infusion through a needle in your arm. Sacituzumab govitecan is delivered this way. 

How Effective Are Biologics?

Biologics are effective treatments. Many clinical studies have found these medicines can improve survival and lessen the chances that the cancer will come back. Here are some key findings:

Are Biologics Safe?

Biologics are generally considered safe. Sometimes, they pose fewer risks than other treatments because they may not kill as many healthy cells.

Still, certain biologic medicines can trigger serious or even life-threatening side effects.  

Here are some possible problems:

• CDK4/6 inhibitors can cause life-threatening inflammation of the lungs, known as interstitial lung disease or pneumonitis. These medicines can also increase your risk for serious infections.
• The mTOR inhibitor everolimus can cause serious infections.
• The PI3K inhibitor alpelisib can lead to a severe skin reaction that causes peeling and blistering. 
• In rare cases, people who take PARP inhibitors can get blood cancer, like myelodysplastic syndrome or acute myeloid leukemia (AML). 

Who Should Not Take Biologics?

Your doctor will tell you about the usual rules for each biologic drug. Some are only to be used after other treatments have been tried. Others are an option if your cancer has spread or you can’t have surgery. 

You also may not be able to get biologic treatments if you are pregnant or breastfeeding. That’s because many of these therapies can hurt the baby.

How Much Do Biologics Cost?

Biologics can be pricey. 

Your out-of-pocket costs will depend on the treatment, how long you need it, and your insurance plan. Every insurance policy is different, so you’ll want to talk to your company about what they will cover. 

Here are some ways you can help manage the expenses:

Try a biosimilar. Biosimilar medicines are generally between 15%-35% cheaper than biologics.  

Look for an assistance program. Many pharmaceutical companies offer patient assistance programs, coupons, or copay cards to make their medicines more affordable. These discounts are available to people with or without health insurance. You can ask your doctor about these programs or visit different drug websites to learn more.

Clinical Trials of Biologics for HR+ Breast Cancer

Clinical trials are studies that look at the safety and effectiveness of new treatments. 

Several new biologic treatments are being evaluated in clinical trials. If you join a study, you might have access to a biologic medicine that isn’t otherwise available. 

If you’re interested in a clinical trial, you can:

Talk to your doctor. Ask your provider about any clinical trials that may help you.

Search databases. Some websites provide detailed lists of clinical trials near you. Clinicaltrials.gov, the National Cancer Institute, and Breastcancer.org are some sites to check out. Often, you can find the contact information for the head investigator and research coordinator near the bottom of the page.

Find a patient navigator. This professional can offer support and help you locate clinical trials. Your local hospital might connect you with a navigator. Or you can contact an organization like the American Cancer Society or Lazarex Cancer Foundation. 

Is a Biologic Right for Me?

If your tumor tests positive for specific characteristics, a biologic may be part of your treatment plan.

Here’s a recap of the what your doctor might think about when they’re considering whether to prescribe a biologic:

Your tumor’s gene status. PARP inhibitors are options for tumors that have a BRCA mutation, and the medicine alpelisib can help those that are HER2-negative with a PIK3CA gene mutation.

Stage of your breast cancer. Some biologics are given for early-stage cancers, while others are reserved for advanced disease. 

Your past treatments. FDA protocols may require you to try certain other therapies before you can get a biologic. 

Cost. Whether you can afford the medicine may be something to think about before you start on biologic.

Your health and treatment goals. Doctors will typically consider your medical history and overall condition before they prescribe a biologic. Your personal desires are also an important part of the treatment decision. 

If you think you might benefit from a biologic, talk to your doctor. Ask about the pros and cons, specifically. In many cases, biologic medicines are an effective treatment option for people with HR+ breast cancer.