HER2 Breast Cancer: The Basics About This Specific Subtype

By: Shalmali Pal

From: medpagetoday.com

Breast cancer is a complex disease with numerous classifications. Understanding risk factors such as age, family history, genetic mutations such as breast cancer gene 1/breast cancer gene 2 (BRCA1/BRCA2opens in a new tab or window), and lifestyle factors is crucial for risk assessment.

In general, the key types of breast canceropens in a new tab or window are the following:

• Invasive ductal carcinoma

• Invasive lobular carcinoma

• Noninvasive ductal carcinoma in situ

• Invasive inflammatory breast cancer

• Invasive and noninvasive Paget’s disease of the breast

• Invasive medullary, mucinous, and papillary breast cancer

Breast cancer cells are also classified by the presence of certain receptors that influence treatment. The human epidermal growth factor receptor 2opens in a new tab or window (HER2) protein is a receptor on the surface of cells that helps regulate cell growth and division. HER2 is also known as ERBB2 (erb-b2 receptor tyrosine kinase 2). The HER2 gene is often mutated or amplified in breast cancer.

HER2-positive means there is an overexpression of the HER2 protein, which promotes cancer growth. Targeted therapies are used to block the HER2 protein. HER2-positive breast cancer is relatively common, accounting for approximately 15-20% of all breast cancers.

HER2-negative breast cancer accounts for about 80% of all breast cancer tumors, including some that are hormone receptor-positive or triple-negative. Triple-negative breast canceropens in a new tab or window (TNBC), a subtype that lacks estrogen receptors, progesterone receptors, and HER2 receptors, tends to be more aggressive and challenging to treat.

HR-positive/HER2-negative is the most common subtype of breast cancer in women. HR-positive/HER2-negative metastatic breast cancer is distinct in its response to hormone therapies due to the presence of estrogen and/or progesterone receptors, and it lacks HER2 overexpression, which affects the treatment options.

This subtype tends to have a more favorable prognosis compared with other subtypes like TNBC or HER2-positive breast cancer, but the metastatic nature still requires careful management with systemic therapies to control the disease’s spread.

HER2-low breast cancer is a subset of HER2-negativeopens in a new tab or window disease. Research is ongoingopens in a new tab or window to better classify it as a distinct subtype, detect it, and treat it optimally.

HER2 Testing

HER2 tumor marker tests are used to determine whether breast cancer is HER2 positive or negative. Patients are candidates for HER2 testing if the cancer is invasive, metastatic, and/or recurrent.

The tissue for HER2 testing is retrieved during biopsy, with testing done via immunohistochemistry and/or fluorescence in situ hybridization (FISH).

Many HER2-targeting therapies require pre-treatment HER2 testing. This information will help guide decisions to make the most effective treatment course.

Treatments

Because these cancers are fueled by hormones, they are often treated effectively with hormone-blocking therapies (endocrine therapy) to block or lower the amount of estrogen in the body, preventing it from fueling cancer cell growth.

Optionsopens in a new tab or window include:

• Aromatase inhibitors: For postmenopausal women, these drugs block the enzyme aromatase, which produces estrogen

• Selective estrogen receptor modulators (SERMs): These drugs block estrogen from binding to estrogen receptors in breast tissue. Tamoxifen is a common SERM used in premenopausal and postmenopausal women

• Ovarian suppression: For premenopausal women, treatments to stop the ovaries from producing estrogen (e.g., luteinizing hormone-releasing hormone agonists, surgical removal of ovaries)

Targeted therapy is another treatment pathwayopens in a new tab or window. Although the cancer is HER2-negative, certain targeted therapies may be used in combination with hormone therapy, particularly in advanced or metastatic settings, as well as some early disease stages. These include:

• Cyclin-dependent kinases (CDK4/6) inhibitors, such as palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). These drugs help stop cancer cells from dividing and are often used as first-line treatment for metastatic HR-positive/HER2-negative breast cancer

• PI3K inhibitors, such as alpelisib (Piqray) and inavolisib (Itovebi), may be used in metastatic HR-positive/HER2-negative breast cancer with specific genetic mutations (PIK3CA)

• AKT inhibitors such as capivasertib (Truqap) are used in metastatic HR-positive/HER2-negative breast cancer after progression on other endocrine therapies. This treatment is specifically indicated for patients with one or more PIK3CA, AKT1, or PTEN alterations.

The prognosis for patients with HR-positive/HER2-negative breast cancer is generally favorable; patients with early-stage HR-positive/HER2-negative breast cancer typically have high 5-year survival ratesopens in a new tab or window of about 96%.

HR-positive breast cancers also have a good prognosis, with survival rates >90%opens in a new tab or window when the disease is diagnosed early and treated appropriately. However, HR-positive disease does have a higher risk of late recurrence.