HER2-negative negative breast cancer means that the cancerous cells do not contain high levels of the protein HER2. Many treatment options are 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 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 HER2-negative breast cancers, which occur for reasons other than a faulty HER2 gene. It lists the treatment options 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. There is also a newer category called HER2-low.
These cancer types have various subtypes, as outlined below.
HER2-low breast cancer
This is because newer, more detailed testing methods can detect a person’s HER2 status in more detail.
The IHC (ImmunoHistoChemistry) test measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample.
An IHC score of more than 3 means the tumor is HER2 positive. For years, professionals classified any score lower than 3 as HER2-negative breast cancer.
Now, doctors refer to cancer with HER2 levels that are between 1 and 2 as HER2-low. HER2-low accounts for
This category makes it easier for doctors to perform targeted therapy on the cancer.
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 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.
LA breast cancer
According to some reports, around 40% 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
LB breast cancer
Some reports estimate that 15% to 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
- HER2
- estrogen
- progesterone
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 years
- premenopausal people
Learn more about triple-negative breast cancer.
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
- symptoms
- previous treatments
- overall health
People with HER2-negative breast cancer may need:
- surgery
- chemotherapy
- radiation therapy
- bisphosphonates
- a combination of these treatments
Surgery
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
Chemotherapy drugs destroy cancer cells by restricting their ability to divide and grow.
Chemotherapy is
Radiation therapy
This treatment uses high intensity X-rays to destroy cancer cells.
Bisphosphonates
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.
Antiestrogen therapy
Antiestrogen therapy works by preventing estrogen from attaching to the estrogen receptors of breast cancer cells.
The four different types of antiestrogen therapy are:
The type of antiestrogen therapy a person receives depends on various factors, including:
- the stage of 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
Targeted therapies focus on specific genetic mutations that affect a cancer’s growth and spread. Doctors usually combine these drugs with hormone therapy.
Treatments for HR-positive and 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:
In males, doctors combine targeted therapy with a gonadotropin-releasing hormone analog. In females who have not yet gone through menopause, doctors combine targeted therapy with 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 already discussed in this article:
Immunotherapy
Immunotherapy drugs, such as pembrolizumab (Keytruda), help the body’s immune system attack cancer cells.
Antibody-drug conjugates
Doctors also use targeted therapies to treat specific genetic mutations in triple-negative breast cancer. Antibody-drug conjugates are medications that attach to and destroy cancer cells, and they are gaining rapid speed in breast cancer.
The medications sacituzumab govitecan-hziy (Trodelvy) and trastuzumab deruxtecan (Enhertu) are antibody-drug conjugates that have
PARP inhibitors
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.
Cancer survival rate refers to the percentage of people who are alive after a certain amount of time following initial diagnosis.
For example, the 5-year relative survival rate refers to the percentage of people who will still be alive after 5 years of their diagnosis, relative to the general population.
The survival rate for breast cancer depends on many factors, including the grade and stage of the cancer.
The following
- 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
The stage of a person’s cancer at diagnosis is an important factor affecting the outlook, as treatment is typically more effective in the early stages.
As of
- 99% for localized disease
- 86% for regional disease
- 30% for distant disease
Breast cancer survival also varies by tumor subtype:
- 94% for HR+/HER2-
- 91% for HR+/HER2+
- 85% for HR-/HER2+
- 77% for HR-/HER2-
The 5-year relative survival rate is 90% or more for all subtypes that receive a diagnosis in the localized stage.
There are three main types of HER2-negative breast cancer: HR-positive, triple-negative, and HER2-low. 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 can speak with their doctor for more in-depth information about their individual treatment plans and outlook.