Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer is the most common type of breast cancer. About 70% of all breast cancer cases are HR+/HER2-. You can break down its name to better understand what this means:
- Hormone receptor positive (HR+) means each breast cancer cell has (is positive for) certain protein molecules on its surface. These proteins bind to the hormones estrogen and progesterone to trigger specific processes within the cell. Breast tumor cells may be positive for estrogen receptors (ER+), progesterone receptors (PR+), or both (ER/PR+). Most breast cancers (about 80%) are either ER+ or ER/PR+.
- HER2- means the breast cancer cells have very few or no HER2 proteins on their surface. In normal cells, HER2 proteins help control growth. When cancer cells don’t have HER2 receptors, they tend to grow more slowly. They’re less likely to recur (come back) or spread to other parts of your body than cancer cells that have many HER2 proteins on their surface.
Knowing your HR/HER2 status helps your doctor choose the best treatment avenues for managing your disease.
But alongside this information, your doctor will also want to know what types of genetic mutations your breast cancer may have. A genetic mutation is a permanent change in the DNA that makes up a gene.
Genetic Mutations in HR+/HER2- Breast Cancer
Some of your genes help control when cells grow or divide to make new cells, some repair mistakes in DNA, and some cause cells to die when they need to. If these genes aren’t working the way they should, your risk of getting cancer can go up. Mutations can also affect how your cancer responds to certain treatments.
BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (BRCA2) are two of the better-known examples of gene mutations that affect your breast cancer risk and treatment. But there are many others, including mutations in:
PIK3CA. This gene aids in cell growth, division, and survival. PIK3CA mutations are some of the most common mutations in breast cancer. Up to 40% of HR+/HER2- breast tumors have this mutation. Researchers think there could be a link between having a PIK3CA mutation and having cancer that spreads beyond your breasts to your lymph nodes.
AKT1 genes are part of the same pathway PIK3CA genes are, and they also affect cell growth, division, and survival. Mutations in this gene can result in more aggressive breast cancer tumors and may mean your cancer won’t respond to standard treatments.
PTEN stands for “phosphatase and TENsin homolog.” It’s a gene that helps stop tumors from growing by controlling how fast the cells divide. It also makes damaged cells self-destruct before they can become cancer cells. PTEN also plays a role in helping cells stick together, which can help prevent cancer from spreading. When you have a mutation in this gene, these processes can’t happen like they normally do.
What Causes HR+/HER2- Breast Cancer Mutations?
PIK3CA and AKT1 mutations are somatic mutations. This means they happen after you’re born, and they aren’t gene changes you get from your parents. Most PTEN mutations are also somatic, but a small number of breast cancer cases come from inherited PTEN mutations, which you’re born with.
Some gene mutations happen as the tumor is forming—a process called tumorigenesis. Others happen as your disease progresses.
How Do Doctors Diagnose HR+/HER2- Breast Cancer Mutations?
In order to diagnose your breast cancer as HR+/HER2-, your doctor will do biomarker testing. A biomarker is anything biological that you can measure with a test to tell you more about your body or a disease in your body. You can use biomarker tests to diagnose disease, see how treatment is working, or help predict the outcome of disease. Hormone receptors are biomarkers.
To diagnose HR/HER2 status, you need a tumor biopsy. Your doctor will use a needle to take out some of your cancer cells for testing. In some cases, you may be able to do a “liquid biopsy,” which uses a standard blood sample instead of a tissue sample.
Immunohistochemistry (IHC) test. This is the most common biomarker test doctors use for checking HR status. This test uses antibodies linked to enzymes to see if hormone receptors are present or absent. The reaction that happens when the antibody attaches to the hormone receptor causes a change in color that doctors can see in a microscope. This tells them the receptors are there and you’re HR+.
To diagnose genetic mutations in your cancer, your doctor can do other tests on your biopsied samples, including:
Polymerase chain reaction (PCR) test. This lab technique makes millions of copies of specific sections of DNA very quickly. This allows doctors to study the samples in greater detail and check for genetic mutations.
Next-generation sequencing. This technology can sequence (figure out the order of the individual units) of molecules and look for mutations.
Who’s Most at Risk of HR+/HER2- Breast Cancer Mutations?
People assigned female at birth (AFAB) who are under 40 are at a higher risk of getting HR+/HER- breast cancer with specific gene mutations such as BRCA1, BRCA2, and PTEN.
Research on the P1K3CA mutation shows that people of European descent are much more likely than any other demographic to get it. More studies on more diverse populations are needed.
How Do HR+/HER2- Breast Cancer Mutations Affect Treatment?
Having certain genetic mutations helps guide your doctor’s treatment decisions.
If you have advanced breast cancer that’s HR+/HER2-, and if you have mutations in PIK3CA, AKT1, or PTEN, you may need specific targeted treatments such as:
- Alpelisib (Piqray)
- Capivasertib (Truqap)
- Everolimus
- Inavolisib (Itovebi)
You may also need a hormone drug called fulvestrant along with other medications.
Questions to Ask Your Doctor
As you learn more about your HR+/HER2- breast cancer mutations, use your doctor as a primary source for information.
You might ask your doctor:
What’s the hormone receptor status of my cancer?
What’s the HER2 status of my cancer?
Should I have genetic testing done for my cancer?
Will insurance pay for my genetic testing?
How do I get a copy of my results?
How will the results affect my treatment options?
How will we know if the treatment is working?
Will my genetic testing results affect my insurance coverage?
Show Sources
Photo Credit: Science Photo Library/Getty Images
SOURCES:
National Cancer Institute: “Cancer State Facts: Female Breast Cancer Subtypes,” “HER2 Negative,” “Biomarker.”
Penn Medicine Abramson Cancer Center: “Hormone Receptor-Positive (HR+) Breast Cancer.”
American Cancer Society: “Gene Changes and Cancer,” “Other Breast Cancer Gene, Protein, and Blood Tests,” “Questions to Ask Your Doctor About Breast Cancer.”
Nature: “PIK3CA mutations in endocrine-resistant breast cancer.”
Biomedicines: “Targeting PI3K/AKT/mTOR Pathway in Breast Cancer: From Biology to Clinical Challenges.”
MedlinePlus: “PIK3C gene,” “PTEN Gene.”
Cleveland Clinic: “PCR Test,” “Immunihistochemistry.”
National Human Genome Research Institute: “Polymerase Chain Reaction (PCR).”
Cancer Biology and Medicine: “Next-generation sequencing and its clinical application.”
Annals of Oncology: “Genomic characterization of hormone receptor-positive breast cancer arising in very young women.”
JCO Precision Oncology: “Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations.”
