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What to know about HER2-negative breast cancer

HER2-negative breast cancer suggests that the cancerous cells do not have high amounts of the protein HER2. There are a variety of therapy options for this form of breast cancer, but the prognosis varies.

Understanding an HR-positive or HER2-negative

Human epidermal growth factor receptor 2 is abbreviated as “HER2.” It could be referring to the HER2 gene or the protein that the gene produces.

HER2 receptors are proteins found on the surface of breast cells. They normally aid in the regulation of healthy breast tissue growth and repair.

When the HER2 gene malfunctions and starts generating too many copies of itself, HER2 proteins on the surface of breast cells are overproduced. This can lead to cancer that is HER2-positive.

This page offers an overview of HER2-negative breast tumors, which are cancers that develop for reasons other than a defective HER2 gene.

We detail the treatment choices for various forms of HER2-negative cancers, as well as the prognosis and survival rates.

Diagnosis

A doctor will need to ascertain the type of breast cancer a person has in order to make a diagnosis. This entails extracting a small amount of breast tissue for testing during surgery or a biopsy.

Testing indicates which genes and proteins are involved in the progression of cancer. This aids in determining the best therapy alternatives.

Types

The presence or lack of hormone receptors on the surface of cancer cells is used to differentiate HER2-negative breast cancer into two types in most studies:

  • hormone receptor-positive (HR-positive) breast cancer
  • triple-negative breast cancer

Hormones such as estrogen and progesterone have a function in the development of healthy breast tissue. Individual protein receptors on the surface of breast cells exist for each hormone. Hormones are taken up by the receptors, which tell the cells to expand.

When a cancer is HR-positive, the cells proliferate and multiply by using estrogen, progesterone, or both. When a malignancy is classified as triple-negative, it lacks these hormone receptors.

As we’ll see below, there are several subtypes of these cancers:

Luminal (HR-positive) breast cancers

Breast cancers that grow in the inner, or luminal, cells are known as Luminal Breast Cancers. The mammary ducts are lined by these cells.

HR-positive Luminal cancers are those that involve at least one type of hormone receptor.

Luminal A (LA) and Luminal B (LB) are the two kinds of luminal breast cancer (LB).

The main difference between the two types is that LA cells have a lower concentration of a protein known as Ki-67. This protein regulates the rate at which tumor cells develop. As a result, LA malignancies grow more slowly than LB cancers and have a better prognosis.

Luminal A breast cancer

According to certain research, LA breast cancer accounts for 30–45 percent of all breast cancers.

The following are some of the characteristics of LA cancer:

  • cells that are HER2-negative
  • cells that test positive for estrogen receptors
  • lower levels of Ki-67
  • low-grade tumors

Luminal B breast cancer

According to some estimates, LB breast cancer accounts for 10–20 percent of all breast cancers.

HER2-negative or HER2-positive LB cancers exist. It is also characterized by 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 10–15% of all breast cancers are triple-negative. Triple-negative breast cancer tests negative for three receptors:

  • 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
  • premenopausal people

General treatments

Several factors influence the type of treatment a person receives, 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

Surgery, chemotherapy, radiation therapy, bisphosphonates, or a combination of these treatments may be required for those with HER2-negative breast cancer.

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 medications work by limiting cancer cells’ capacity to divide and develop.

For triple-negative breast cancers, chemotherapy is more common than for luminal breast cancers. Both forms, however, may require chemotherapy, especially if the tumor is larger than 1 centimeter (cm) ,

Radiation therapy

High-intensity X-rays are used to kill cancer cells in this treatment.

Bisphosphonates

Some people may be prescribed bisphosphonates by their doctors to help prevent breast cancer from spreading to their bones.

Bisphosphonate medications include zoledronic acid and sodium clodronate, to name a few.

Specific treatments

Some luminal breast cancer treatments will not be appropriate for triple-negative breast cancer, and vice versa.

Specific treatment methods for both categories are listed in the sections below:

Options for luminal (HR-positive) breast cancer

Hormone therapy is given to the majority of people who have luminal or other forms of HR-positive breast cancer. This is referred to as endocrine therapy by others.

Because it is HR-negative, triple-negative breast cancer does not respond to hormone therapy.

Anti-estrogen therapy

Anti-estrogen therapy works by inhibiting estrogen from binding to breast cancer cells’ estrogen receptors.

Anti-estrogen therapy is divided into four categories:

  • 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

HR-positive breast cancer may not respond to the therapy listed above in some circumstances. As a result, for more advanced cancer, a doctor may consider one of the hormone therapy listed below:

  • progestin medications, such as megestrol (Megace)
  • an anabolic steroid, such as fluoxymesterone (Halotestin)

Targeted therapies

Targeted therapies target specific genetic alterations that contribute to the growth and spread of cancer. These medications are frequently used in conjunction with hormone therapy.

Treatments for HR-positive, HER2-negative metastatic breast cancer target and block CDK4/6, a protein thought to drive tumor growth, according to specialists.

CDK4/6 inhibitors include the following:

  • abemaciclib (Verzenio)
  • palbociclib (Ibrance)
  • ribociclib (Kisqali)

Targeted therapy is paired with a gonadotropin-releasing hormone analog or ovarian suppression in men and women who have not yet reached menopause.

Triple-negative breast cancer treatment options

The following therapies may be used instead of or in addition to the more general cancer treatments listed above for some persons with triple-negative breast cancer:

Immunotherapy

Immunotherapy medications like atezolizumab (Tecentriq) and pembrolizumab (Keytruda) assist the immune system in attacking cancer cells.

Cancer cells can hide from the immune system thanks to proteins like the PD-L1 protein. Tecentriq inhibits the development of PD-L1, a protein that the immune system uses to recognize and kill cancer cells.

Therapy that is specific to the patient

In triple-negative breast cancer, doctors also use targeted medicines to treat specific genetic abnormalities. For those who have already had two treatments, the medication sacituzumab govitecan-hziy (Trodelvy) was approved in 2020. It’s an antibody drug conjugate, which means it binds to cancer cells and kills them.

Inhibitors of PARP

Triple-negative breast cancer is caused by a mutation in the BRCA1 or BRCA2 genes in certain patients. PARP inhibitors may be beneficial to these folks.

Poly ADP-ribose polymerase is the acronym for poly ADP-ribose polymerase. It’s a DNA-repair enzyme that works in both healthy and malignant cells.

PARP inhibitors prevent the PARP enzyme from working properly. Cancers with a BRCA1 or BRCA2 gene mutation have a tougher time surviving DNA damage as a result of this. Olaparib (Lynparza) and talazoparib are two examples (Talzenna).

Outlook

The percentage of people who are alive after a given amount of time after being diagnosed with cancer is referred to as the cancer survival rate.

The survival rate for breast cancer is determined by a variety of factors, including the tumour’s grade and stage.

Under a microscope, the grade indicates how aberrant the malignant cells appear. Cells that appear abnormal proliferate and spread more quickly.

The cancer’s stage refers to how big it is and how far it has spread. This is normally measured on a scale of 0 to 4 by doctors.

Cancers at stage 0 are ones that are still in the early stages of development and have not spread to neighboring cells. Cancers in stage 4 are the most advanced and have the worst prognosis.

Cancer survival rates are also influenced by the following factors:

  • whether the cancer is HR-positive or HR-negative
  • the person’s age at diagnosis
  • the person’s overall health

Cancer-specific survival rates

Survival statistics for several forms of breast cancer are included in a 2019 overview of breast cancer therapy.

HR-positive cancers, such as luminal cancers, had a greater survival rate than triple-negative breast cancers, according to the findings.

Stage 1 cancer survival rates

Stage 1 HR-positive breast cancer has a 5-year survival rate of roughly 99 percent.

Furthermore, because LA breast cancer has lower Ki-67 levels than LB breast cancer, it grows more slowly. As a result, clinicians are more likely to discover LA cancer at an earlier stage, giving patients a somewhat better prognosis.

Stage 1 triple-negative breast cancer has an 85 percent 5-year survival rate. These cancers have a faster growth rate and respond to fewer treatments.

Metastatic cancer survival rates

Breast cancers can spread to other parts of the body, which is known as metastasis. The prognosis for metastatic cancer is substantially worse.

Following a diagnosis of metastatic cancer, people with HR-positive breast cancer usually live for another 4–5 years. Following the same diagnosis, people with triple-negative breast cancer may live an extra year.

It’s crucial to keep in mind that survival statistics are estimations based on the outcomes of people who have had cancers that are similar to yours.

However, cancer survival rates are influenced by a variety of complex circumstances. These variables will differ from one person to the next.

Summary

HR-positive breast cancer and triple-negative breast cancer are the two main kinds of HER2-negative breast cancer. Treatments for various cancers differ in some ways.

Breast cancers that are HR-positive have a better prognosis than cancers that are triple-negative.

People can use survival rates to estimate how successful their treatment will be. People should, however, speak with their doctor for further information regarding their specific treatment plan and prognosis.

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