The importance of HER2 status for metastatic breast cancer treatment

By WP Creative Group

MARCH 22, 2023

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For about 60 percent of patients previously diagnosed with HER2-negative metastatic breast cancer, there may be a treatment available.

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In the world of breast cancer, a thorough account of many details and data points is the key to life-changing diagnoses. Binary information can be useful in making treatment decisions based on these complex sets of information: It can only be one, or the other. While concrete duality may simplify decision-making, it can also obscure pertinent information. The long-held human epidermal growth factor receptor 2 (HER2) diagnostic standard of positive or negative has been revealed as one of those dualities that masks the full picture of possible treatment.

“We’ve taken HER2 status to be kind of binary, but what we’re beginning to see is that it’s most likely a more continuous measure,” said Dr. Maryam Lustberg, chief of breast oncology at Yale Cancer Center. In other words, the older ways of determining HER2 status have evolved.

A treatment granted FDA breakthrough designation for patients in this liminal space called HER2-low has shown promising results. For some of those previously diagnosed as HER2-negative, the changing landscape of the HER2 spectrum could mean a modified prognosis and hope.

This hope comes from a better understanding of HER2 proteins which cause breast cancer cells to grow quickly.

“It’s really important to know if a cancer is HER2-driven,” said Dr. Sara Tolaney, chief of the division of breast oncology at Dana Farber Cancer Institute, because those cancers are highly receptive to HER2-targeted treatment. “We know we can give HER2-positive patients drugs that could shut off the growth factor driving these tumor cells and stop growth.” This means, as far as breast cancer diagnoses go, HER2-positive is a hopeful one.

Historically, only patients with HER2-positive tumors had HER2-directed targeted therapies available to them. “The whole HER2-negative population was excluded from those therapies,” Lustberg said. About 80-85 percent of breast cancer patients test negative for HER2 expression, meaning only 15-20 percent of patients were candidates for HER2-targeted therapies.¹

Prior to the identification of HER2-low, the distinction between HER2-positive and negative had long been categorized with immunohistochemistry (IHC) scores from 0 to 3+ to indicate the overexpression of HER2 proteins. Patients with IHC scores of 0 and 1+ were classified as HER2-negative, while IHC scores of 3+ were classified as HER2-positive. Those with IHC scores of 2+ would be further tested to ultimately determine HER2 status.² An IHC score shapes a patient’s entire course of treatment so it’s critical for patients to know their numbers and HER2 status.

A presentation at 2022’s American Society of Clinical Oncology Meeting (ASCO) introduced another HER2 status into the lexicon: HER2-low. The trial showed that many patients with IHC scores 1+ and 2+/ISH-, previously considered HER2-negative, actually exhibited low expressions of HER2 protein.³

Both Lustberg and Tolaney would encourage patients previously diagnosed as HER2-negative to ask their doctors about retesting for HER2-low. “There’s growing recognition to not assume somebody’s [tumor is] really HER2-negative and at least take another look,” said Lustberg.

And of course, it takes time for revised standards to spread into practice. “Because our culture has been to bucket people into HER2-positive or HER2-negative all these years, it’s going to take time for this to shift to be more universally applied to patients,” said Tolaney.

What is ENHERTU? 

ENHERTU^® (fam-trastuzumab deruxtecan-nxki) is a prescription medicine used to treat adults who have: 

HER2-low breast cancer that cannot be removed by surgery or that has spread to other parts of your body (metastatic), and who have received a prior chemotherapy: 

• For metastatic disease, or
• Your disease has returned during or within 6 months of completing adjuvant chemotherapy (after surgery). 

Your healthcare provider will perform a test to make sure ENHERTU is right for you.

It is not known if ENHERTU is safe and effective in children.

ENHERTU can cause serious side effects including lung problems that may be severe, life threatening or that may lead to death; low white blood cell count; heart problems that may affect your heart’s ability to pump blood; or harm to an unborn baby. See Important Safety Information below.

The discovery of HER2-low means more than a reclassification of long-observed cancer subtypes and more than a hopeful headline. For about 60 percent of previously diagnosed HER2-negative metastatic breast cancer patients, it may mean eligibility for a HER2-targeted therapy.⁴ “It’s the beginning of a revolution in terms of therapy,” said Lustberg. “So I do feel excited about that—excited about that for our patients.”

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Important Safety Information

What is the most important information I should know about ENHERTU? ENHERTU can cause serious side effects, including: 

Lung problems that may be severe, life-threatening or that may lead to death. If you develop lung problems your healthcare provider may treat you with corticosteroid medicines. Tell your healthcare provider right away if you get any of the following signs and symptoms: 

• Cough 
• Trouble breathing or shortness of breath
• Fever
• Other new or worsening breathing symptoms (e.g., chest tightness, wheezing)

Low white blood cell counts (neutropenia). Low white blood cell counts are common with ENHERTU and can sometimes be severe. Your healthcare provider will check your white blood cell counts before starting ENHERTU and before starting each dose. Tell your healthcare provider right away if you develop any signs or symptoms of an infection or have fever or chills during treatment with ENHERTU.

Heart problems that may affect your heart’s ability to pump blood. Your healthcare provider will check your heart function before starting treatment with ENHERTU. Tell your healthcare provider right away if you get any of the following signs and symptoms:

Your healthcare provider will check you for these side effects during your treatment with ENHERTU. Your healthcare provider may reduce your dose, delay treatment or completely stop treatment with ENHERTU if you have severe side effects.

Harm to your unborn baby. Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with ENHERTU.

• If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with ENHERTU.
• Females who are able to become pregnant should use effective birth control (contraception) during treatment with ENHERTU and for 7 months after the last dose.
• Males who have female partners that are able to become pregnant should use effective birth control (contraception) during treatment with ENHERTU and for 4 months after the last dose.

Before you receive ENHERTU, tell your healthcare provider about all of your medical conditions, including if you:

• Have lung or breathing problems.
• Have signs or symptoms of an infection.
• Have or have had any heart problems.
• Are breastfeeding or plan to breastfeed. It is not known if ENHERTU passes into your breast milk. Do not breastfeed during treatment with ENHERTU and for 7 months after the last dose.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. 

How will I receive ENHERTU? 

• You will receive ENHERTU into your vein through an intravenous (IV) line by your healthcare provider.
• ENHERTU is given 1 time every three weeks (21-day treatment cycle).
• Your healthcare provider will decide how many treatments you need.
• Your healthcare provider will give you medicines before your infusion to help prevent nausea and vomiting.
• Your healthcare provider may slow down or temporarily stop your infusion of ENHERTU if you have an infusion-related reaction, or permanently stop ENHERTU if you have severe infusion reactions.
• If you miss a planned dose of ENHERTU, call your healthcare provider right away to schedule an
• appointment. Do not wait until the next planned treatment cycle.

What are the possible side effects of ENHERTU? 

ENHERTU can cause serious side effects. See “What is the most important information I should know about ENHERTU?” 

The most common side effects of ENHERTU when used at the 5.4 mg/kg dose include: 

ENHERTU may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility. 

These are not all of the possible side effects of ENHERTU. Call your doctor for medical advice about side effects. You may report side effects to Daiichi Sankyo at 1-877-437-7763 or to FDA at 1-800-FDA-1088. 

Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

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Sources:

1. Breast Cancer Research Foundation’s HER2-Low Breast Cancer Explained
2. American Cancer Society’s Breast Cancer HER2 Status
3. Memorial Sloan Kettering Cancer Center’s ASCO 2022: Practice-Changing Findings Identify HER2-Low as a Targetable Subset of Breast Cancer, Redefining Treatment for More Than 60 Percent of HER2-Negative Metastatic Breast Cancer Patients
4. Memorial Sloan Kettering Cancer Center’s ASCO 2022: Practice-Changing Findings Identify HER2-Low as a Targetable Subset of Breast Cancer, Redefining Treatment for More Than 60 Percent of HER2-Negative Metastatic Breast Cancer Patients

ENHERTU^® is a registered trademark of Daiichi Sankyo Company, Limited. ©2023 Daiichi Sankyo, Inc. and AstraZeneca. 
PP-US-ENB-2383  02/23