What to know about HER2-negative breast cancer
HER2 stands for human epidermal growth factor receptor 2. The term "HER2" may refer to the HER2 gene or to the protein HER2, which the gene makes.
HER2 proteins are receptors that sit on the surface of breast cells. They usually help control the growth and repair of healthy breast tissue.
However, when the HER2 gene becomes faulty and starts making too many copies of itself, it results in an overproduction of HER2 proteins on the surface of breast cells. This can result in HER2-positive cancer.
We list the treatment options available for different types of HER2-negative cancer, along with information on prognosis and survival rates.
To make a diagnosis, a doctor will need to determine the type of breast cancer a person has. This involves removing a small piece of the breast tissue during surgery, or a biopsy, and sending it to a lab for testing.
Testing reveals which types of genes and proteins are involved in the cancer's development. This helps determine the most appropriate treatment options.
HR-positive and triple-negative are the types of HER2-negative breast cancer.
Most studies divide HER2-negative breast cancer into two types based on the presence or absence of hormone receptors on the surface of cancer cells.
These types are called hormone receptor-positive (HR-positive) breast cancer and triple-negative breast cancer.
Estrogen and progesterone are hormones that play a role in the growth of healthy breast tissue. Each hormone has its own individual protein receptors, which sit on the surface of breast cells. The receptors take up hormones, which instruct the cells to grow.
These cancer types have various subtypes, as we outline below:
Luminal breast cancers
Luminal breast cancers develop in the inner, or luminal, cells. These cells line the mammary ducts.
Luminal cancers are HR-positive, meaning that they involve at least one type of hormone receptor.
There are two types of luminal breast cancer: Luminal A (LA) and Luminal B (LB).
The key difference between the two types is that LA cells contain less of a protein called Ki-67. This protein controls the growth rate of tumor cells. LA cancers, therefore, tend to grow more slowly than LB cancers, and they have a better prognosis.
Luminal A breast cancer
According to some studies, around 30–70% of breast cancers are LA breast cancer.
LA cancer tends to have the following characteristics:
- cells that are HER2-negative
- cells that test positive for estrogen receptors
- lower levels of Ki-67
- low grade tumors
Luminal B breast cancer
Some reports estimate that 10–20% of breast cancers are LB breast cancer.
LB cancer can be either HER2-negative or HER2-positive. It also tends to have the following characteristics:
- cells that test positive for estrogen receptors
- higher levels of Ki-67
- higher grade tumors
- larger tumors
- a higher chance of spreading to a lymph node
Triple-negative breast cancer
Approximately 20% of breast cancers are triple-negative. Triple-negative breast cancer tests negative for three receptors: HER2, estrogen, and progesterone.
Triple-negative breast cancer is more common in:
- women who have a mutation in the BRCA1 gene
- black women
- women below the age of 40
- premenopausal women
People with HER2-negative breast cancer may need to undergo:
Most people with breast cancer have surgery to remove the tumor. There are two main types of surgery:
Breast conserving surgery: This involves the removal of the tumor and some of the surrounding healthy breast tissue.
Mastectomy: This involves the total removal of the affected breast.
Chemotherapy is more common for triple-negative breast cancers than luminal breast cancers. However, both types may require chemotherapy — particularly if the tumor measures more than 1 centimeter (cm) across.
This treatment uses high intensity X-rays to destroy cancer cells.
Doctors may recommend that some people take bisphosphonates to help prevent breast cancer from spreading to the bones.
Some examples of bisphosphonate drugs include zoledronic acid and sodium clodronate.
Some of the treatments for luminal breast cancer will not be appropriate for triple-negative breast cancer, and vice versa.
In the sections below, we list specific treatment options for both types:
Options for luminal breast cancer
A doctor can recommend the best treatment options for specific types of breast cancer.
Most people with luminal or other types of HR-positive breast cancer receive hormone therapy. Some people call this endocrine therapy.
Because triple-negative breast cancer is HR-negative, it does not respond to hormone therapy.
Anti-estrogen therapy works by preventing estrogen from attaching to the estrogen receptors of breast cancer cells.
The four different types of anti-estrogen therapy are:
- selective estrogen-receptor response modulators, such as Tamoxifen
- aromatase inhibitors
- estrogen-receptor downregulators, such as fulvestrant (Faslodex)
- luteinizing hormone releasing agents, including goserelin (Zoladex) and leuprolide (Lupron), prevent the ovaries from producing estrogen
The type of anti-estrogen therapy a person receives depends on various factors, including:
- the stage of the breast cancer
- whether the person has any other medical conditions
- whether the person has been through menopause
A person usually continues hormone therapy for at least 5 years.
Other hormone therapies
In some cases, HR-positive breast cancer may not respond to the above treatments. If this is the case, a doctor may recommend one of the following hormone therapies for more advanced cancer:
- progestin medications, such as megestrol (Megace)
- an anabolic steroid, such as fluoxymesterone (Halotestin)
Options for triple-negative breast cancer
Some people with triple-negative breast cancer may receive the following therapies instead of, or in addition to, the more general cancer treatments detailed above:
Immunotherapy drugs, such as atezolizumab (Tecentriq) help the body's immune system attack cancer cells.
Some proteins, such as PD-L1 protein, help cancer cells hide from the immune system. Tecentriq stops the production of PD-L1, and this allows the immune system to detect and kill cancer cells.
For some people, triple-negative breast cancer develops due to a mutation in the BRCA1 or BRCA2 gene. These people may benefit from the use of PARP inhibitors.
PARP stands for poly ADP-ribose polymerase. It is an enzyme that repairs DNA damage in both healthy and cancerous cells.
PARP inhibitors interfere with the PARP enzyme. This makes it harder for cancers with a BRCA1 or BRCA2 gene mutation to survive DNA damage.
A person's age and overall health can influence their prognosis.
Cancer survival rate refers to the percentage of people who are alive after a certain amount of time following initial diagnosis.
The survival rate for breast cancer depends on many factors, including the grade and stage of the cancer.
The grade is a measure of how abnormal the cancerous cells appear under a microscope. Cells that appear more abnormal tend to grow and spread faster.
The stage refers to the size of the cancer and how far it has spread. Doctors usually measure this on a scale from 0 to 4.
Stage 0 cancers are those in the earliest stage of development and have not yet spread to nearby cells. Stage 4 cancers are the most advanced and have the poorest prognosis.
The following factors also influence cancer survival rates:
- whether the cancer is HR-positive or HR-negative
- the person's age at diagnosis
- the person's overall health
Cancer-specific survival rates
A 2019 review of breast cancer treatments features survival rates for different types of breast cancer.
According to the report, HR-positive cancers such as luminal cancers have higher survival rates than triple-negative breast cancers.
Stage 1 cancer survival rates
The 5-year survival rate for stage 1 HR-positive breast cancer is around 99%.
Also, because LA breast cancer involves lower levels of Ki-67, this cancer tends to grow more slowly than LB breast cancer. This means that doctors usually detect LA cancer at an earlier stage, resulting in a slightly better prognosis.
The 5-year survival rate for stage 1 triple-negative breast cancer is 85%. These cancers tend to grow more quickly and respond to fewer treatments.
Metastatic cancer survival rates
Sometimes, breast cancers spread, or metastasize, to other parts of the body. Metastatic cancer has a much poorer prognosis.
People with HR-positive breast cancer usually survive an additional 4–5 years following a diagnosis of metastatic cancer. People with triple-negative breast cancer may survive an additional year following the same diagnosis.
It is important to remember that survival rates are estimates based on the outcomes of people with similar cancers.
However, many different and complex factors can influence cancer survival rates. These factors will differ from person to person.
There are two main types of HER2-negative breast cancer: HR-positive breast cancers and triple-negative breast cancer. Some of the treatments for these cancers differ.
HR-positive breast cancers have a better prognosis than triple-negative breast cancers.
Survival rates can give people an estimate of how successful their treatment may be. However, people should speak to their doctor for more in-depth information about own treatment plan and prognosis.