HER2-negative negative breast cancer means that the cancerous cells do not contain high levels of the protein HER2. There are many treatment options available for this type of breast cancer, but the outlook can vary.
“HER2” stands for human epidermal growth factor receptor 2. It 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 overproduces HER2 proteins on the surface of breast cells. This can result in HER2-positive cancer.
This article provides a general overview of a group of breast cancers known as HER2-negative cancers, which occur for reasons other than a faulty HER2 gene.
We list the treatment options available for different types of HER2-negative cancer, along with information on outlook 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 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.
Most studies divide HER2-negative breast cancer into
- hormone receptor-positive (HR-positive) breast cancer
- 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.
When a cancer is HR-positive, the cells use estrogen, progesterone, or both to grow and replicate. When a cancer is triple-negative, it means that these hormone receptors are absent.
These cancer types have various subtypes, as we outline below:
Luminal (HR-positive) 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 outlook.
Luminal A breast cancer
According to some studies, around 30–45% 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
Triple-negative breast cancer is more common in:
- people who have a mutation in the BRCA1 gene
- Black people
- people below the age of 50
- premenopausal people
The type of treatment a person receives depends on several factors, including:
- the stage of cancer
- whether and where the cancer has spread
- whether there are hormone receptors in the cells
- genetic mutations
- previous treatments
- overall health
People with HER2-negative breast cancer may need surgery, chemotherapy, radiation therapy, bisphosphonates, or a combination of these treatments.
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 drugs destroy cancer cells by restricting their ability to divide and grow.
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.
The following sections list specific treatment options for both types:
Options for luminal (HR-positive) breast cancer
Triple-negative breast cancer does not respond to hormone therapy because it is HR-negative.
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
Other hormone therapies
In some cases, HR-positive breast cancer may not respond to the above treatments. Consequently, 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)
Targeted therapies focus on specific genetic mutations that play a role in a cancer’s growth and spread. These drugs are usually combined with hormone therapy.
Treatments for HR-positive, HER2-negative metastatic breast cancer target and block a specific protein known as CDK4/6, which experts believe stimulates tumor growth.
Examples of CDK4/6 inhibitors include:
- abemaciclib (Verzenio)
- palbociclib (Ibrance)
- ribociclib (Kisqali)
In men or in women who have not gone through menopause, targeted therapy is combined with a gonadotropin-releasing hormone analog or ovarian suppression.
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) and pembrolizumab (Keytruda) 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, which allows the immune system to detect and kill cancer cells.
Doctors also use targeted therapies to treat specific genetic mutations in triple-negative breast cancer. The drug sacituzumab govitecan-hziy (Trodelvy) gained approval in 2020 for people who have already received at least two treatments. It is an antibody drug conjugate, meaning it attaches to and destroys 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. Examples include olaparib (Lynparza) and talazoparib (Talzenna).
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 outlook.
- whether the cancer is HR-positive or HR-negative
- the person’s age at diagnosis
- the person’s overall health
Learn more about breast cancer staging.
Cancer-specific survival rates
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
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 outlook.
The 5-year survival rate for stage 1 triple-negative breast cancer is
Metastatic cancer survival rates
Sometimes, breast cancers spread, or metastasize, to other parts of the body. Metastatic cancer has a much poorer outlook.
People with HR-positive breast cancer usually survive an additional
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 cancer and triple-negative breast cancer. Some of the treatments for these cancers differ.
HR-positive breast cancers have a better outlook than triple-negative breast cancers.
Survival rates can give people an estimate of how successful their treatment may be. However, people should speak with their doctor for more in-depth information about their own treatment plan and outlook.