Hormone Receptor Positive HER2 Negative Breast Cancer

Hormone receptor positive HER2 negative breast cancer is the most common type of breast cancer, accounting for about 70% of all cases. This type responds to hormone-blocking treatments because the cancer cells have receptors for estrogen or progesterone, but don’t have high levels of the HER2 protein.

Table of contents

• What is Hormone Receptor Positive HER2 Negative Breast Cancer?
• How This Cancer Grows
• Symptoms
• Causes and Risk Factors
• Diagnosis and Testing
• Treatment Options
• Prognosis

What is Hormone Receptor Positive HER2 Negative Breast Cancer?

Hormone receptor positive HER2 negative breast cancer is a specific type of breast cancer where the cancer cells have special proteins on their surface called hormone receptors. These receptors respond to the body’s natural hormones, estrogen and progesterone, which can fuel the cancer’s growth^[1][4].

This type of cancer is also called HR+/HER2-. The “HR+” means the cancer cells test positive for either estrogen receptors (ER+), progesterone receptors (PR+), or both. The “HER2-” means the cancer cells don’t have high levels of a protein called human epidermal growth factor receptor 2 (HER2), which is a different type of protein that can cause cancer cells to grow quickly^[1][9].

This is the most common form of breast cancer, representing approximately 70-80% of all breast cancer cases^[3][4][11]. The majority of patients with a new breast cancer diagnosis have early stage disease^[3].

How This Cancer Grows

In hormone receptor positive breast cancer, the cancer cells have tiny proteins on their surface that act like receivers. When estrogen or progesterone in your body attach to these receptors, they send signals that cause the cancer cells to divide and the tumor to grow^[4][15].

A breast cancer is considered ER-positive if at least 1% of cells stain positive for estrogen receptors. Similarly, it’s considered PR-positive if at least 1% of cells show progesterone receptor staining^[3][11]. Some cancers are positive for both receptors, while others may be positive for only one^[4].

There is a newly defined category called ER Low Positive tumors, which have low levels of ER positivity (1-10%). These tumors tend to behave more like hormone receptor negative cancers^[3][11].

Symptoms

The symptoms of hormone receptor positive HER2 negative breast cancer are the same as with breast cancer in general. Signs to look out for include^[1][9][16]:

• Changes in your breast’s size or shape
• A new lump or hardened area in or near your breast or armpit that doesn’t change in response to your periods
• Skin changes affecting your breast or nipple, including dimpled, puckered, scaly, itchy or discolored (reddish, purple or unusually dark) skin
• Nipple discharge, including bloody or clear fluid
• A nipple that pulls inward

It’s important to remember that breast cancer doesn’t always cause changes you can see. Also, many of these changes are common in noncancerous conditions. This is why it’s important to get regular breast cancer screenings. See a healthcare provider if you’re unsure if changes are signs of cancer or a noncancerous condition^[1][9].

Causes and Risk Factors

Hormone receptor positive HER2 negative breast cancer forms when the DNA in breast cells changes and becomes cancer cells. The cells divide uncontrollably and form tumors^[1][9].

Experts don’t know what causes the mutations that lead to tumors in this type of breast cancer. However, they’ve identified several factors that may increase your breast cancer risk^[1][9][16]:

• Inherited genetic mutations: While there isn’t a mutation that causes HER2-related breast cancers specifically, inheriting the BRCA1 or BRCA2 gene mutations increases your overall breast cancer risk
• Personal or family history of breast cancer: A previous breast cancer diagnosis increases your risk, as does having biological relatives with breast cancer (especially a parent, sibling or child)
• Long-term exposure to high levels of estrogen or progesterone: Getting your first period at an early age or starting menopause late increases your lifetime exposure to sex hormones. Some forms of hormone therapy can increase your risk

Diagnosis and Testing

Whether patients present with symptoms or screen-detected breast abnormalities, a tissue biopsy of a suspicious area should be performed. Standard evaluation is carried out, including an assessment of ER, PR and HER2 status if cancer is detected^[3][11].

Your hormone receptor status is determined through biomarker testing on a tumor sample, typically during a biopsy or surgery. The test uses a tool called immunohistochemistry (IHC), which measures how many hormone receptors are present on the cancer cells. Results are reported as a percentage — higher percentages mean the tumor is more responsive to hormones^[4][15].

Understanding the characteristics of cancer cells, or biomarkers, helps providers determine which treatments will work best^[1][9]. Knowing whether your breast cancer is hormone receptor positive helps doctors guide your treatment plan and determine which therapies might be most effective in preventing the cancer from growing^[4][15].

If breast cancer returns or spreads, your hormone receptor status can change. For example, if the first tumor was treated with hormone therapies, a cancer that has returned may become resistant to that therapy. In other cases, a tumor may undergo changes to gain hormone receptor presence that it didn’t have before. That’s why doctors may recommend retesting the cancer’s biomarkers if it comes back or progresses^[4][15].

Treatment Options

Significant advances have been made in the management of early stage hormone receptor positive HER2 negative breast cancer, resulting in improved survival outcomes^[3][11]. When a tumor is hormone receptor positive, it responds to treatments that block the activity or production of hormones^[4][15].

Hormone Therapy

Hormone therapy (also called hormonal therapy, hormone treatment, or endocrine therapy) slows or stops the growth of hormone-sensitive tumors by blocking the body’s ability to produce hormones or by interfering with the effects of hormones on breast cancer cells^[7].

Several strategies are used to treat hormone-sensitive breast cancer^[7]:

• Blocking ovarian function: In premenopausal women, estrogen levels can be reduced by eliminating or suppressing ovarian function through surgery, radiation, or drugs
• Aromatase inhibitors (AIs): Drugs like anastrozole, exemestane, and letrozole that lower estrogen levels
• Selective estrogen receptor modulators: Drugs like tamoxifen and toremifene that block estrogen from connecting to cancer cells
• Selective estrogen receptor degraders: Drugs like fulvestrant that work differently than other hormone therapies

Hormonal therapies have a lower risk of serious side effects than chemotherapy, so you may have a better quality of life during treatment. You can take them as pills or in a shot^[12][20].

CDK4/6 Inhibitors

CDK4/6 inhibitors are a class of drugs that target particular enzymes called CDK4 and CDK6. These have been a tremendous breakthrough in the past 5 years. Three agents have been approved: palbociclib, ribociclib, and abemaciclib^[6][14].

All three drugs are indicated for initial endocrine-based therapy in postmenopausal women with an aromatase inhibitor, and also for disease progression following endocrine therapy with fulvestrant^[6][14].

Targeted Therapies

Targeted therapies block certain proteins or molecules that drive the growth and spread of cancer cells. These drugs are also called precision medicine because your doctor prescribes a certain drug based on your genes or the proteins associated with your specific cancer^[12][20].

Targeted therapies for hormone receptor positive HER2 negative breast cancer include^[12][20]:

• PARP inhibitors like olaparib and talazoparib: These drugs stop a protein from repairing cancer cells, so the cells die. They’re given to women who have a mutation in the BRCA gene
• PIK3CA inhibitors: These drugs target mutations in the PIK3CA gene

Chemotherapy

Chemotherapy is medicine that kills cancer cells. You can take it as pills or get it through an IV. Many different chemotherapy drugs are used, either alone or in combination, to treat hormone receptor positive HER2 negative breast cancer^[12][20].

Other Treatments

Treatment may also include surgery to remove the tumor, and radiation therapy. The specific treatment plan depends on the stage of cancer, other characteristics of the tumor, and individual patient factors^[3][11].

Prognosis

Hormone receptor positive breast cancers tend to grow more slowly than hormone receptor negative cancers^[4][15]. Your hormone receptor status affects almost every part of your treatment plan^[4][15].

Research has shown that hormone receptor positive HER2 negative tumors generally have better outcomes compared to other breast cancer types, especially when treated with appropriate hormone-blocking therapies^[5]. However, outcomes can vary based on whether both estrogen and progesterone receptors are positive, with balanced expression (both ER+ and PR+) generally associated with better outcomes than unbalanced expression^[5].

The role of adjuvant endocrine therapy, the duration of treatment, and the management of treatment-related side effects are all important factors to consider in the management of this disease^[3][11].