HER2-Positive Breast Cancer: Symptoms, Treatment & Research

How Serious is HER2-positive Breast Cancer?

The challenges of Triple Negative Breast Cancer (TNBC) and Inflammatory Breast Cancer (IBC) should be cause for concern but not despair. Oncological research has made strides in treating similarly aggressive forms. Readers of our previous “How Serious is…” articles might recognize it from one of the promising researched treatments for IBC: HER2.

What is HER2-positive Breast Cancer?

HER2-positive Breast Cancer is a distinct subtype of breast cancer characterized by the overexpression of the human epidermal growth factor receptor 2 (HER2) protein. An overexpression in this case refers to increased production of that gene, specifically gene amplification. In healthy cells, HER2 is a normal part of cell biology, regulating cell growth, division, and repair; there is usually one HER2 gene on each of a cell’s chromosomes. The overexpression caused by the cancer results in far more than one HER2 gene per chromosome, which in turn sends out signals to have other nearby cells start manufacturing more HER2 genes as well.

This protein surplus promotes cancer cell growth, leading to more aggressive tumors. HER2-positive breast cancer was first identified in the late 1980s when researchers discovered that approximately 15-20% of breast cancer cases exhibited an overproduction of the HER2 protein. This revelation led to a significant shift in breast cancer classification and treatment strategies.

How Rare is HER2-positive Breast Cancer?

The statistics of HER2 Breast Cancer have remained rather substantial, accounting for 15-20% of all breast cancer cases; the Breast Cancer Research Foundation tabulated that there were 297,790 cases of this type of breast cancer in the USA alone in their 2024 article “HER2-Positive Breast Cancer: Testing, Treatment, Research”. Appropriately, it is regarded with great wariness due to its rapid growth and increased likelihood of recurrence. However, advancements in targeted therapy have significantly improved outcomes for patients diagnosed with this provocative subtype.

That said, individuals with the following risk factors will still want to consider scheduling multiple breast cancer screenings a year just to be sure:

• Age: More commonly diagnosed in younger women compared to other breast cancer types. Vexingly, the classification of “younger” here is defined as women under the age of 50 with “peak” cases happening within the 40-50 year-old age range. Rather than worrying too much over this rather wide range, patients should instead assess whether this status is complimented by the other HER2-positive breast cancer risk factors here.
• Gender: Though male patients with the below risk factors can still be afflicted with this type of breast cancer, HER2 is usually more prevalent in women.
• Ethnicity: Studies have shown that black women are more likely to be diagnosed with HER2-positive breast cancer than other ethnicities. A 2015 manuscript in Cancer Epidemiol Biomarkers titled “Racial disparities in breast cancer diagnosis and treatment by hormone receptor and HER2 status” observed that Hispanic/Latina women may be similarly susceptible.
• Genetics: HER2-positive breast cancer can be linked to hereditary mutations like BRCA1 and BRCA2, though those mutations are breast cancer risk factors regardless of type. HER2 is more commonly associated with TP53 mutations.
• Hormonal Factors: Early menstruation (especially if this happens before the age of 12), late menopause (age 55 and beyond), not having children, having children after the age of 30, not breastfeeding one’s children, long-term hormone replacement therapy, and postmenopausal hormone therapy may increase the risk of HER2 breast cancer.
• Dense Breast Tissue: Again, this is a fairly standard risk factor regardless of the type of breast cancer, and should be regarded with the same scrutiny as it usually would.
• Lifestyle Factors: Obesity, excessive alcohol consumption, and lack of physical activity may contribute to the risk of getting this type of breast cancer.

What Are the Unique Symptoms and Challenges of HER2-positive Breast Cancer?

HER2-positive breast cancer often presents with symptoms similar to those of other breast cancer types, but its rapid growth makes these signs more pronounced

Symptoms of HER2-positive Breast Cancer:

As a debatable trade-off to being more explicit, unlike inflammatory breast cancer symptoms, these can manifest as early as stage 2 or even stage 1, allowing for earlier detection and treatment:

• A palpable lump in the breast or underarm.
• Changes in breast size, shape, or texture.
• Unusual nipple discharge.
• Breast pain or tenderness.
• Skin changes, including redness or dimpling.

However, not all cases have the symptoms occur at early stages.

Challenges in Diagnosing HER2-positive Breast Cancer:

While mammograms, ultrasounds, and biopsies are standard diagnostic tools for breast cancer, additional tests are needed to confirm HER2 status:

• Immunohistochemistry (IHC): Measures the level of HER2 proteins in cancer cells.
• Fluorescence in situ hybridization (FISH): Detects HER2 gene amplification, providing a more definitive diagnosis.

Since HER2-positive tumors grow quickly, early detection is critical to prevent metastasis. Delayed diagnosis can lead to a more advanced disease stage, requiring more aggressive treatment.

Is HER2-positive Breast Cancer Better or Worse Than Typical Breast Cancer?

HER2-positive breast cancer was once considered one of the most aggressive breast cancer types due to its high growth rate and increased likelihood of spreading beyond the breast. It was also far more common than the likes of similarly speedy sorts of breast cancer like inflammatory breast cancer; triple-negative breast cancer would not be formally recognized until the early 2000s, about two decades after HER2-positive breast cancer was discovered.

However, the development of targeted therapies, such as Trastuzumab (Herceptin) and Pertuzumab (Perjeta), has dramatically improved survival rates.

Comparison to Other Breast Cancer Types:

• Growth Rate: Faster than hormone receptor-positive breast cancer.
• Metastasis Tendency: Higher risk of spreading to distant organs, including the brain, liver, and lungs.
• Treatment Response: While HER2-positive breast cancer is aggressive, it responds well to targeted therapies, leading to better prognoses than those of triple-negative breast cancer.
• Recurrence Risk: Without targeted therapy, recurrence rates for this type of breast cancer are high, but with proper treatment, long-term remission is achievable.

Does HER2-positive Breast Cancer Require Unique Treatments?

HER2-positive breast cancer requires a specialized treatment approach that differs from other breast cancer subtypes.

1. Targeted Therapy

• Trastuzumab (Herceptin): A monoclonal antibody that blocks HER2 receptors, slowing tumor growth.
• Pertuzumab (Perjeta): Often used in combination with Herceptin to enhance treatment efficacy.
• Ado-Trastuzumab Emtansine (Kadcyla): A drug-conjugate therapy that combines targeted therapy with chemotherapy.
• Neratinib (Nerlynx) and Tucatinib (Tukysa): Used for advanced cases or when cancer becomes resistant to other HER2-targeted treatments.

Side Effects: Fatigue, heart-related complications, diarrhea, and infusion reactions.

2. Chemotherapy

• Often used in combination with targeted therapy to shrink tumors before surgery.
• Common side effects include nausea, hair loss, and lowered immunity.

3. Hormonal Therapy (for HER2-Positive, Hormone Receptor-Positive Cases)

• If the cancer is also estrogen receptor (ER)-positive or progesterone receptor (PR)-positive, hormonal therapies like Tamoxifen or Aromatase Inhibitors may be added to the treatment plan.

4. Surgery

• Lumpectomy: Removal of the tumor while preserving the breast.
• Mastectomy: Complete removal of the breast if the cancer is extensive.

5. Radiation Therapy

• Used post-surgery to eliminate remaining cancer cells.
• Common side effects include skin irritation, fatigue, and swelling.

What is the Survival Rate for HER2-positive Breast Cancer?

Prognosis and Survival Statistics

The prognosis for HER2-positive breast cancer has improved significantly due to targeted therapies, though the survival rates for Stage 4 take a substantial dip compared to those in stage 3.

• Stage 1: 90-99% 5-year survival rate.
• Stage 2: 80-90% 5-year survival rate.
• Stage 3: 50-70% 5-year survival rate.
• Stage 4 (Metastatic): 20-30% 5-year survival rate, though newer treatments are improving these numbers.

Factors Affecting Survival Rates:

• Early Detection: The sooner HER2-positive cancer is diagnosed, the better the prognosis.
• Response to Targeted Therapy: Thanks to refinements in treatments, most patients respond well, significantly improving survival rates.
• Molecular Subtype: HER2-positive, hormone receptor-positive cases may have better outcomes due to additional treatment options.

HER2-Positive Breast Cancer Remedy Research

HER2-positive breast cancer, once considered pervasive and daunting, is now one of the most treatable breast cancer subtypes thanks to breakthroughs in targeted therapy. The development of HER2 inhibitors, antibody-drug conjugates, and immunotherapy has dramatically changed patient outcomes.

Recent Breakthroughs in HER2-positive Breast Cancer Treatment:

1. Enhertu (Trastuzumab Deruxtecan)
   Enhertu, an antibody-drug conjugate (ADC), combines a HER2-targeting antibody with a chemotherapy payload to deliver treatment directly to cancer cells while sparing healthy tissue. It has demonstrated remarkable efficacy in clinical trials for metastatic HER2-positive breast cancer, even in patients who had stopped responding to previous HER2-targeted therapies.
2. Tucatinib (Tukysa)
   HER2-positive breast cancer has a higher tendency to spread to the brain, making it difficult to treat with standard therapies. Tucatinib, a HER2-selective tyrosine kinase inhibitor (TKI), has shown strong results in shrinking brain metastases and extending survival in patients with HER2-positive disease. The HER2CLIMB trial demonstrated that patients receiving Tucatinib had significantly improved overall survival rates, even when cancer had spread to the brain.
3. HER2-Targeted Bispecific Antibodies
   Researchers are developing bispecific antibodies that can simultaneously bind to HER2 and another cancer marker, boosting the immune system’s ability to attack cancer cells. Zanidatamab, one such promising drug, is currently in phase 2 clinical trials and has already shown strong tumor reduction in HER2-positive patients.
4. mRNA-Based Cancer Vaccines
   Inspired by the success of mRNA vaccines in fighting COVID-19, researchers are now exploring mRNA-based cancer vaccines for HER2-positive breast cancer. These vaccines are designed to train the immune system to recognize and destroy HER2-positive cancer cells, reducing the risk of recurrence.
5. Checkpoint Inhibitors
   Checkpoint inhibitors like Pembrolizumab (Keytruda) are being tested in combination with HER2-targeted therapies to enhance the immune system’s ability to attack HER2-positive tumors.
6. CAR-T Cell Therapy
   Chimeric Antigen Receptor (CAR)-T cell therapy, which has been highly successful in treating blood cancers, is now being adapted for HER2-positive breast cancer. In early-phase clinical trials, HER2-specific CAR-T cells have shown promising results in shrinking tumors that have become resistant to conventional treatments.
7. HER2-Directed Radiopharmaceuticals
   Radiopharmaceutical therapy is an emerging field where radioactive particles are attached to HER2-targeting antibodies to directly irradiate cancer cells while sparing healthy tissue. Drugs like Zr-89-Trastuzumab are currently being studied for their ability to deliver precise radiation to HER2-positive tumors, especially in cases where cancer has spread beyond the breast.

With continuous advancements in cancer treatment, the outlook for HER2-positive breast cancer patients continues to improve.